bromochloroacetic-acid and Testicular-Neoplasms

Gonadal germ cell tumors continue to be the cause of diverse, diagnostically challenging issues for the pathologist, and their correct resolution often has major important therapeutic and prognostic implications. They are academically interesting because of the biological diversity exhibited in the two gonads and variation in frequency of certain neoplasms. The most dramatic examples of the latter are the frequency of dermoid cyst in the ovary compared to the testis and the reverse pertaining to embryonal carcinoma. Within the teratoma group, there is strong evidence that ovarian and prepubertal testicular teratomas are derived from benign germ cells, a pathogenesis that likely applies also to the rare dermoid cysts and uncommon epidermoid cysts of the testis. In contrast, postpubertal testicular teratomas derive from malignant germ cells, specifically representing differentiation within a preexistent nonteratomatous cancer. As expected, given the foregoing, teratomas in boys are clinically benign, whereas in postpubertal males they are malignant, independent of their degree of immaturity. On the other hand, immaturity is an important finding in ovarian teratomas, irrespective of age, although its significance in children has recently been challenged. It is usually recognized on the basis of embryonic-appearing neuroepithelium, which shows mitotic activity and apoptosis in contrast to differentiated neuroepithelial tissues, which may occur in mature ovarian teratomas. Rarely it is based on the presence of cellular, mitotically active glial tissue. Fetal-type tissues alone are not sufficient for a diagnosis of immature teratoma. Further differences between the teratomatous tumors in the two gonads are the relative frequency of monodermal teratomas in the ovary in contrast to the testis, where only one subset, carcinoids, is seen with any frequency. When uncommon somatic-type malignancies (usually squamous cell carcinoma) occur in mature cystic teratomas of the ovary, this is a de novo form of malignant transformation; similar tumors in the testis, a very rare event, represent overgrowth of teratomatous elements that originated from malignant, nonteratomatous germ cell tumors and, therefore, had previously undergone malignant transformation. Germinomas may have several unusual features in each gonad; these include microcystic arrangements that suggest yolk sac tumor, tubular patterns that mimic Sertoli cell tumor, apparent increased cytological atypia that

Topics: Diagnosis, Differential; Female; Germinoma; Humans; Immunohistochemistry; Keratin-7; Keratins; Ki-1 Antigen; Male; Neoplasms, Germ Cell and Embryonal; Organic Cation Transport Proteins; Ovarian Neoplasms; Proto-Oncogene Proteins c-kit; Teratoma; Testicular Neoplasms

Herein is a review of clear cell neoplasms of selected sites in the urinary tract and male reproductive system, including the kidney, the urinary bladder, testis, epididymis, and prostate. Clear cell cytoplasmic alteration in neoplasms at these sites is a relatively common light microscopic finding. Examples of such neoplasms with clear cell change include the clear cell type of renal cell carcinoma, clear cell adenocarcinoma of urethra and bladder, the classic type of seminoma, papillary cystadenoma of the epididymis, and well-differentiated adenocarcinoma of the prostate. Of importance, numerous non-neoplastic benign entities may also manifest cleared cytoplasm and therefore are presented in the differential in this review. Indeed, knowledge of the neoplastic and non-neoplastic entities displaying clear cell change at each anatomic site should enable the surgical pathologist to approach the differential diagnosis of these conditions in a more logical and rigorous fashion.

Topics: Adenocarcinoma; Alkaline Phosphatase; Biomarkers, Tumor; Carcinoma, Renal Cell; Diagnosis, Differential; Genital Neoplasms, Male; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Male; Mucin-1; Prostatic Neoplasms; Testicular Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms

The fifteenth case of malignant Sertoli cell tumour is reported and the literature is reviewed. The reported case was unilateral with lung metastases. Immunohistochemical examination showed positive staining reaction within the tumour cells for vimentin and cytokeratin, while AFP, HCG, PLAP, EMA and CEA were not found, which is in accordance with the staining pattern found in normal Sertoli cells.

Topics: Aged; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Sertoli Cell Tumor; Testicular Neoplasms; Vimentin

Mammalian animal toxicity of ochratoxin A (OTA) has focused largely in the past half-century on pigs because of initial recognition of it as a principal cause of intermittent growth suppression and renal disease caused by mouldy feed. Subsequent classical toxicology has used laboratory rodents because renal pathology in pigs raised questions concerning possible involvement in the human idiopathic bilateral renal atrophy of Balkan endemic nephropathy for which OTA was a focus of attention for human nephropathy through 1980s and into 2000s. Emphasis on human nephropathy has more recently concerned the plant metabolite aristolochic acid. Recognition that agricultural management can often minimise food and feed-stuff spoilage by OTA-producing Aspergilli and Penicillia has moderated some of the risks for animals. Legislation for human food safety combined with sophisticated analysis generally provides safety in the developed world. Chronic experimental exposure of male rats, in the absence of clinical dis-ease, specifically causes renal cancer. The possibility of this as a unique model for the human has generated considerable experimental evidence which may be more directly relevant for carcinogenesis in the complex kidney than that obtained from biochemical toxicities in vitro. Nevertheless, there does not appear to be any case of human renal or urinary tract cancer for which there is verified etiological proof for causation by OTA, contrary to much claim in the literature. To contribute to such debate, histopathology review of OTA/rat renal cancers, augmented where appropriate by immune profiles, has been completed for all remaining tumours in our research archive. Overall consistency of positivity for vimentin, is matched with occasional positives either for CD10 or the cytokeratin MNF 116. The current situation is discussed. Suggestion that OTA could cause human testicular cancer has also been challenged as unsupported by any experimental findings in rats, where the Leydig cell tumour immune profile does not match that of human germ cell neoplasms.

Topics: Animals; Carcinogenicity Tests; Dietary Exposure; Humans; Keratins; Kidney Neoplasms; Male; Neprilysin; Ochratoxins; Rats, Inbred F344; Risk Assessment; Risk Factors; Testicular Neoplasms; Time Factors; Vimentin

Primary mediastinal germ cell tumors are uncommon tumors that can pose diagnostic difficulties due to their morphologic spectrum and unusual site. Immunohistochemistry plays an increasing role in the diagnosis of these tumors. Whereas the immunophenotype of testicular yolk sac tumors (YST) is rather well known, the opposite is true for primary mediastinal YST leading us to investigate the immunohistochemical features of 14 such neoplasms. Fourteen cases of primary mediastinal YST were reviewed and representative whole tissue sections were selected for immunohistochemical analysis using antibodies directed against CAM5.2, SALL4, OCT3/4, glypican-3, CD30, α-fetoprotein (AFP), CD117, placental alkaline phosphatase (PLAP), GATA-3, and CDX2. The percentage of positive tumor cells and the intensity of staining were evaluated and scored. All cases (100%) showed strong and diffuse expression of CAM5.2 and SALL4, 10 cases (71%) reacted with glypican-3 and AFP in a patchy manner, 5 cases (36%) showed focal positivity with PLAP and GATA-3, 4 cases (29%) showed staining for CDX2, 3 (21%) showed expression of CD117, and a single case was positive for CD30 (7%). None of the cases showed any staining for OCT3/4. Primary mediastinal YST appear to have a similar immunohistochemical phenotype as their testicular counterparts. Coexpression of CAM5.2, SALL4, glypican-3, and AFP provides the best support for YST differentiation; however, it has to be noted that none of these markers is specific for these tumors and immunohistochemical results will always have to be interpreted in the context of morphologic, clinical, and radiologic information.

Topics: Adolescent; Adult; Biomarkers; Cell Differentiation; Child; Diagnosis, Differential; Endodermal Sinus Tumor; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Male; Mediastinal Neoplasms; Middle Aged; Octamer Transcription Factor-3; Testicular Neoplasms; Transcription Factors; Young Adult

A 53-year-old Taiwanese male had several episodes of left epididymitis with hydrocele refractory to antibiotic treatment. Partial epididymectomy plus preventive vasectomy were planned, and, incidentally, an ill-defined nodule was found lying on the tunica vaginalis near the epididymal head. The pathological diagnosis was malignant mesothelioma of the tunica vaginalis testis. Radical orchiectomy with wide excision of the hemi-scrotal wall was performed. So far, there is no evidence of recurrence after more than 3 years of follow-up. Malignant tumor should be considered in the case of recurrent epididymitis refractory to empirically effective antibiotic treatment. Although the nature of this tumor is highly fatal, the malignancy can possibly be cured by early and aggressive surgical treatment.

Topics: Epididymitis; Humans; Keratins; Male; Mesothelioma; Middle Aged; Orchiectomy; Recurrence; Testicular Neoplasms

Topics: Acid Phosphatase; Adult; Choristoma; Humans; Keratins; Male; Prostate; Prostate-Specific Antigen; Protein Tyrosine Phosphatases; Teratoma; Testicular Neoplasms

Adenomatoid tumors are rare benign neoplasms thought to be of mesothelial origin. Although most reported cases arise from the epididymis, rare cases have been reported in the spermatic cord, testicular tunica, ejaculatory ducts, prostate, and suprarenal recess. We describe a 4.5-year-old boy who presented with a relatively asymptomatic right testicular mass that was resected and confirmed to be adenomatoid tumor of the testis by histopathology. Because of its rarity, the clinical and histopathologic aspects are discussed.

Topics: Adenomatoid Tumor; Biomarkers, Tumor; Child, Preschool; Cryptorchidism; Diagnosis, Differential; Humans; Keratins; Male; Organ Sparing Treatments; Teratoma; Testicular Neoplasms; Ultrasonography; Vimentin

A case of benign reactive pseudo-glandular mesothelial hyperplasia arising in the context of chronic vaginitis in presented: morphological and immunohistochemical investigations and differential diagnoses are described.

Topics: Cell Proliferation; Diagnosis, Differential; Humans; Hyperplasia; Keratins; Male; Testicular Diseases; Testicular Hydrocele; Testicular Neoplasms; Young Adult

Desmoplastic small round cell tumors are rare aggressive cancers of adolescence and early adulthood. It has recently been separated from other small round cell tumors because of its pathological characteristics and clinical features. They are usually intra-abdominal tumors affecting young people and have classically been associated with a bad prognosis. However, in recent years there have been reports on desmoplastic small round cell tumors affecting other body regions, including the paratesticular area. We report the case of a 27-year-old male who consulted on a progressive enlargement of the right hemiscrotum. He referred no previous urological symptoms and had no systemic symptomatology. Physical examination revealed a round elastic firm 1-cm mass of the epididymis, which was excised. A computed tomography scan showed a para-aortic mass of 1cm. Histological and immunohistochemical diagnosis confirmed a desmoplastic small round cell tumor. The patient received chemotherapy. Today, 6 months after diagnosis the patient remains well and free of disease. Recent reviews on desmoplastic small round cell tumors affecting the paratesticular area have shown a better prognosis for tumors of this origin compared to abdominal ones. We should include this lesion among the differential diagnosis of paratesticular tumors, mainly in children and adolescents.

Topics: Adolescent; Adult; Cell Division; Child; Epididymis; Humans; Immunohistochemistry; Keratins; Male; Orchiectomy; Reverse Transcriptase Polymerase Chain Reaction; Testicular Neoplasms; Tomography, X-Ray Computed; Treatment Outcome

Immunohistochemical studies of human fetal Sertoli cells (SCs) have shown transient expression of cytokeratin (CK) and desmin (DES) that is replaced after birth by expression of vimentin (VIM) and inhibin-α (INH-α). Human Sertoli cell tumours (SCTs) are characterized by re-expression of CK and DES. The aim of the present study was to evaluate immunohistochemically the expression of VIM, INH-α, CK and DES in normal and neoplastic canine SCs. Normal testicular tissue from three adult dogs, one 6-month-old puppy and two neonatal pups was examined in addition to samples from 21 canine SCTs. VIM was not expressed by neonatal SCs, but was present in SCs from the puppy, the adult dogs and in all SCTs. Conversely, INH-α was expressed by neonatal SCs and most SCTs, but not by normal SCs of adult dogs and the puppy. DES and CK were expressed only by some SCTs. These results show that, contrary to findings in man, canine SCs do not express VIM at the time of birth. SCs from neonatal dogs do express INH-α, but such expression was lost in the puppy and the adult dogs. Canine SCs therefore differ from human SCs, as expression of INH-α characterizes immature SCs, whereas the expression of VIM characterizes mature SCs. Canine SCTs may express CK and DES, suggesting that the neoplastic cells undergo de-differentiation during transformation.

Topics: Animals; Desmin; Dog Diseases; Dogs; Immunohistochemistry; Inhibins; Keratins; Male; Sertoli Cell Tumor; Sertoli Cells; Testicular Neoplasms; Testis; Vimentin

Topics: Acid Phosphatase; Adult; Choristoma; Humans; Keratins; Male; Orchiectomy; Prostate; Prostate-Specific Antigen; Protein Tyrosine Phosphatases; Teratoma; Testicular Neoplasms

Necrotic testicular tumors are relatively frequent and can present a significant diagnostic challenge. Because of differing treatments for seminomas versus nonseminomas, accurate diagnosis is critical. Eleven totally (n=9) or almost totally (n=2) necrotic testicular tumors were retrieved from our consult files. The submitting pathologists favored benign processes in 4 cases, Leydig cell tumor in 1, and lymphoma in 1. The cases were evaluated for histologic features and, when material was available, by immunostaining with 7 antibodies: keratin (AE1/AE3), OCT4, placental alkaline phosphatase, alpha-fetoprotein (AFP), CD117, CD30, and S100. Only distinct reactivity in a cellular distribution in the necrotic zone was considered positive; nuclear reactivity alone was scored for OCT4 and membrane reactivity for CD117 and CD30. Mean patient age was 35 years (range 16-63). Mean tumor size was 19 mm (range 7-53). All patients presented with unilateral testicular masses (6 right, 5 left); 2 also had acute pain. The combination of histologic features, immunostains and, in 1 case, serum AFP permitted classification of 8 tumors (4 seminomas, 3 embryonal carcinomas, 1 yolk sac tumor). Three were not classifiable. The necrotic seminomas lacked associated coarse intratubular calcifications and were positive for OCT4 (4/4) and CD117 (3/3) but negative for keratin (0/4) and CD30 (0/4). The necrotic embryonal carcinomas had associated coarse intratubular calcifications and were positive for keratin (2/3), OCT4 (2/2), and CD30 (3/3). OCT4 stained 1 unclassifiable tumor, which lacked other specific markers. We did not find placental alkaline phosphatase, AFP, and S100 stains useful, although S100 did highlight tumor "ghost" cells in 1 case. Other features in most cases included intratubular germ cell neoplasia (6/11), tubular atrophy/hyalinization (10/11), tumor "ghost" cells (10/11), scar (9/11), and inflammation (10/11). Of the 5 patients with available follow-up, 3 were free of disease at 1, 5, and 8 years after orchiectomy (2 necrotic seminomas and 1 germ cell tumor, unclassified). One patient with yolk sac tumor (age 63 y) developed widespread metastases after 15 months and died of disease. The final case was initially misinterpreted as "testicular infarction, no malignancy" and 16 months later the patient developed a large retroperitoneal seminoma. Most totally necrotic testicular tumors can be placed into clinically important groups by assessment for coarse intratubula

Topics: Adolescent; Adult; alpha-Fetoproteins; Biomarkers, Tumor; Carcinoma, Embryonal; Disease-Free Survival; Endodermal Sinus Tumor; Humans; Immunohistochemistry; Keratins; Ki-1 Antigen; Male; Middle Aged; Necrosis; Octamer Transcription Factor-3; Orchiectomy; Proto-Oncogene Proteins c-kit; Seminoma; Testicular Neoplasms; Young Adult

Topics: Carcinoid Tumor; Cell Differentiation; Cell Division; Chromogranin A; Functional Laterality; Humans; Keratins; Male; Middle Aged; Orchiectomy; Serotonin; Synaptophysin; Testicular Neoplasms

Sertoli cell tumours (SCT) are rare and poorly explored neoplasias, and the genetic features of these uncommon tumours are largely unknown. Data about chromosomal aberrations in human SCT of the testis are very rare. We present in this paper the first molecular-cytogenetic study of SCT of the testis. DNA was isolated from paraffin-embedded tumour material from 11 patients with unilateral SCT. We used comparative genomic hybridisation to investigate changes in DNA copy number. The detected DNA imbalances showed variation from case to case, indicating a high genetic heterogeneity. Chromosomal aberrations were detected in 9 of the 11 tumours evaluated, with 13 losses versus 14 gains. The most frequent aberrations detected were gain of chromosome X (5 of 11 cases) followed by losses of entire or part of chromosomes 2 and 19 in three cases. This study suggests a high variability in histomorphological and genetic patterns. Only gain of the entire chromosome X seems to be a frequent aberration in these tumours. Further studies of these tumour types are necessary to clarify the significance of chromosomal alterations in carcinogenesis of SCT.

Topics: Adult; Aged; Calbindin 2; Child, Preschool; Chromosome Aberrations; Genome, Human; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Infant; Inhibins; Keratins; Male; Middle Aged; Nucleic Acid Hybridization; S100 Calcium Binding Protein G; Sertoli Cell Tumor; Testicular Neoplasms; Vimentin

Correctly diagnosing a metastatic germ cell tumor after chemotherapy may be challenging because of the diverse morphological manifestations of postchemotherapy tumors. Both OCT4 and CD30 are sensitive markers for the identification of primary embryonal carcinomas; however, loss of expression of CD30 (65%) has been reported in metastatic embryonal carcinomas after chemotherapy. The present study was conducted to evaluate the expression patterns of OCT4 and CD30 in postchemotherapy metastatic embryonal carcinomas and to compare their utility as diagnostic tools. Twenty-five cases of metastatic embryonal carcinoma after chemotherapy were immunohistochemically analyzed for CD30, OCT4, and cytokeratin AE1/AE3 expression. The staining intensities and the percentages of positively staining tumor cells were recorded. Nineteen (76%) of 25 cases revealed diffuse, moderate to strong nuclear OCT4 staining in postchemotherapy embryonal carcinomas. Among these 19 OCT4-positive cases, 8 also revealed diffuse and moderate to strong membranous CD30 staining. Seven of these OCT4-positive cases retained focal and weak CD30 expression. The remaining 4 OCT4-positive cases demonstrated a complete loss of CD30 expression. The 19 OCT4-positive cases showed a positive but variable cytokeratin AE1/AE3 expression pattern. Six (24%) of 25 cases were negative for both CD30 and OCT4 but demonstrated diffuse and strong cytokeratin AE1/AE3 staining. OCT4 is a useful diagnostic marker to identify metastatic embryonal carcinomas after chemotherapy, with a better sensitivity than CD30.

Topics: Adult; Antineoplastic Agents; Biomarkers, Tumor; Carcinoma, Embryonal; Cisplatin; Evaluation Studies as Topic; Humans; Keratins; Ki-1 Antigen; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Octamer Transcription Factor-3; Retrospective Studies; Sensitivity and Specificity; Testicular Neoplasms

Adenomatoid tumor with intra-testicular localization is rare. Although most reported cases arise from the epididymis, rare cases have been reported in the testicular tunica, spermatic cord, ejaculatory ducts, prostate and suprarenal recess. Adenomatoid tumors occur in both sexes and are also found in the uterus, ovary and fallopian tubes of the female genital tract. Adenomatoid tumors are benign proliferations of mesothelial origin. We report the case of a 50-year-old male with an adenomatoid tumor of the left testis. Because of its rarity, the clinical, diagnostic and therapeutic aspects as well as the possibilities of testicular preservation are discussed.

Topics: Adenomatoid Tumor; Biomarkers, Tumor; Biopsy; Calbindin 2; Diagnosis, Differential; Humans; Keratins; Male; Middle Aged; Orchiectomy; Prognosis; S100 Calcium Binding Protein G; Testicular Neoplasms; Testis; Tomography, X-Ray Computed; Ultrasonography; Vimentin

The article reports the clinical, histopathological, and immunohistochemical findings of a 1-year-old boy presenting with isosexual pseudoprecocity attributable to a functioning Leydig cell tumor of the testis. The case appears to represent the youngest patient ever recognized with this well-known syndrome. Malignancy features were also for the first time initially assessed using criteria, retrospectively developed from the literature, for metastasizing Leydig cell tumor. All the following were found: infiltrative borders, cellular pleomorphism, high mitotic index (12-14/high-power field), high MIB-1 index (40%), P53 positivity in 50% of the cells, and bcl-2 positivity in 15% of the cells. Immunohistochemistry proved the cells of the tumor to be positive for inhibin, Melan-A, synaptophysin, cytokeratin, and calretinin and negative for S-100 and chromogranin A. Notably, lipochrome and crystals of Reinke were not found in the tumor cells. Although the neoplasm fulfilled the criteria for a potentially metastasizing Leydig cell tumor, there was no evidence of that event having occurred, perhaps as a result of early treatment or as indication that criteria developed for Leydig cell tumor of adults may not apply to children.

Topics: Antigens, Neoplasm; Calbindin 2; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Infant; Inhibins; Keratins; Leydig Cell Tumor; Male; MART-1 Antigen; Neoplasm Proteins; Puberty, Precocious; S100 Calcium Binding Protein G; Synaptophysin; Testicular Neoplasms

Topics: Biomarkers; CA-125 Antigen; Carcinoembryonic Antigen; Cell Differentiation; Cystadenocarcinoma, Papillary; Cystadenocarcinoma, Serous; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Lewis X Antigen; Male; Middle Aged; Mucin-1; Ovary; S100 Proteins; Testicular Neoplasms; Testis

Topics: Cystadenocarcinoma, Mucinous; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucin 5AC; Mucin-2; Mucins; Testicular Neoplasms

The mechanisms of invasive tumour development from pre-invasive CIS are unknown. We examined changes in functional parameters of the tubular wall according to the increase in CIS cells and tubular size. Immunohistochemistry was performed on 37 testicular specimens from 25 patients with carcinoma in situ and/or malignant germ cell tumour for the detection of actin/myosin in myocytes, and laminin/integrin alpha 6 in the basement membrane of seminiferous tubules. Tumour cells were detected by PlAP, Sertoli cells by inhibin alpha and vimentin and by cytokeratin 18/connexin 26 immunoreactivity, which is selectively expressed together with CIS. Areas showing clusters of tumour cells surrounded by a fibrous sheet could be identified as enlarged tubules because of focal Sertoli cell-specific co-expression of inhibin alpha, vimentin, cytokeratin 18, and connexin 26 immunoreaction. These clusters exhibited an intact basement membrane shown by a persistent laminin/integrin alpha 6 immunoreactivity, but myocytes had lost their contractility indicated by the loss of myosin/actin immunoreactivity. They often showed septa originating from the fibrous sheet containing numerous capillaries. Focal areas of syncytiotrophoblastic cells within classical seminoma also expressing inhibin alpha, cytokeratin 18, and connexin 26 could be differentiated from single Sertoli cells within tumor cell clusters by typical hCG but absence of vimentin immunoreactivity. In contrast to the current concept of CIS cells passing the tubular wall, these data provide evidence for an additional theory, i.e. that the switch from pre-invasive CIS to invasive tumour takes place in situ by tubular enlargement due to tumour cell proliferation followed by Sertoli cell degeneration and conversion of the tubular wall into connective tissue.

Topics: Actins; Adult; Basement Membrane; Carcinoma in Situ; Cell Division; Chorionic Gonadotropin; Germinoma; Humans; Immunohistochemistry; Integrin alpha6; Keratins; Laminin; Male; Middle Aged; Seminiferous Tubules; Sertoli Cells; Testicular Neoplasms

Sertoli cell tumor of the testis (not otherwise specified) in a 43-year-old man is reported. Macroscopically, the testicular mass measured 3.0 x 2.3 x 1.5 cm and was well circumscribed. The cut surface was white to tan-gray in color. Neoplastic cells with eosinophilic cytoplasm proliferated with solid and tubular structures. Neoplastic cells focally contained vacuoles of various sizes in the cytoplasm. Cystic formation and cord formation in the hyalinized stroma was also observed. Immunohistochemically, neoplastic cells were positive for cytokeratin 8, chromogranin A and synaptophysin, but neoplastic cells were negative for placental alkaline phosphatase, inhibin-alpha and pancytokeratin. The stroma in the tumor center and capsule contained a significant number of myofibroblasts that were positive for alpha-smooth muscle actin and negative for h-caldesmon, but no CD34-positive stromal cells were detected in the stroma of the tumor center. Ultrastructurally, neoplastic cells had cytoplasmic processes and abundant rough endoplasmic reticulum and lipid droplets in the cytoplasm. However, dense core granules were absent. It is important to differentiate between Sertoli cell tumor and carcinoid tumor because of the positive reaction for neuroendocrine markers in both tumors. Myofibroblasts are a major stromal component of Sertoli cell tumor of the testis.

Topics: Adult; Biomarkers, Tumor; Chromogranin A; Chromogranins; Cytoplasm; Humans; Immunohistochemistry; Inhibins; Keratins; Male; Neurosecretory Systems; Sertoli Cell Tumor; Synaptophysin; Testicular Neoplasms

We describe an unusual case of metastatic choriocarcinoma of the pancreas arising from a regressing testicular mixed germ cell tumor that clinically mimicked a primary pancreatic tumor. A 54-year-old male presented with a 2-month history of progressive upper abdominal pain, weight loss, and jaundice. He also had a history of recurrent epididymitis associated with the presence of a right testicular mass shown to be cystic by ultrasound and stable for at least 10 years. A computed tomography scan showed an isolated 6 cm mass in the head of the pancreas. A pancreaticoduodenectomy was performed. Upon histological examination, the pancreatic tumor showed extensive hemorrhage and necrosis. In the viable area, the tumor was composed of an intimate mixture of mononuclear cytotrophoblast cells and multinucleated syncytiotrophoblasts with vascular invasion. These characteristic features led to the correct diagnosis on frozen section. The cytology of the tumor was nonspecific and suggested undifferentiated carcinoma of the pancreas. The trophoblastic origin of the tumor cells was confirmed by immunohistochemistry staining. The testicular mass showed a regressed mixed germ cell tumor of predominantly seminoma with focal teratoma but without a choriocarcinoma component. In conclusion, we present a rare and unusual case of a regressing testicular mixed germ cell tumor that presented as a primary pancreatic tumor. Cytological features of the pancreatic mass were not specific and raised the possibility of a primary undifferentiated carcinoma of the pancreas. Characteristic histological features of choriocarcinoma led to the correct diagnosis on frozen section. Subsequent resection of the testicular mass confirmed the presence of a cystic and scarring (regressing) mixed germ cell tumor but without evidence of choriocarcinoma.

Topics: Biomarkers; Choriocarcinoma; Chorionic Gonadotropin; Germinoma; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Keratins; Male; Middle Aged; Neoplasm Regression, Spontaneous; Pancreas; Pancreatic Neoplasms; Testicular Neoplasms; Testis

Although intratubular embryonal carcinoma has been described adjacent to invasive embryonal carcinoma, to our knowledge it has not been reported as an isolated finding. We present in this report the histologic and immunohistochemical findings of 2 cases of intratubular embryonal carcinoma. One case was exclusively intratubular embryonal carcinoma without an invasive component in the same testis. A malignant mixed germ cell tumor in the contralateral testis had been previously excised. The second case is predominantly composed of intratubular embryonal carcinoma adjacent to a malignant mixed germ cell tumor. In one case, the intratubular embryonal carcinoma was immunoreactive for CD30, AE1/AE3, cytokeratin 7 focally, and p53. It was negative for cytokeratin 20, p21, and alpha-fetoprotein. These findings are strongly supportive of the opinion that intratubular embryonal carcinoma is the precursor of invasive embryonal carcinoma.

Topics: Adult; Anion Exchange Protein 1, Erythrocyte; Antiporters; Biomarkers, Tumor; Carcinoma in Situ; Carcinoma, Embryonal; Germinoma; Humans; Immunohistochemistry; Keratin-7; Keratins; Ki-1 Antigen; Male; Neoplasms, Multiple Primary; Precancerous Conditions; Testicular Neoplasms; Tumor Suppressor Protein p53

In spite of the high curability rates, rare cases of testicular seminoma behave in an unexpectedly aggressive manner. No effective markers are currently available that can predict such uncommon behavior. We studied 105 cases of testicular seminoma on whom the primary resection was performed at the Memorial Sloan-Kettering Cancer Center, New York, to investigate any relationship between morphology, immunohistochemical features, and clinical/pathological stages. Fifty-nine percent of the cases presented with pT stage 1 and 74 percent with American Joint Committee on Cancer (AJCC) stage I. In univariate analysis, tumor size, mitotic count, and presence of necrosis showed significant associations with pT stage (p = 0.0001, 0.0001, and 0.04, respectively), and the presence of vascular invasion (p = 0.0001, 0.0001, and 0.02, respectively). In multivariate analysis, both the tumor size and mitotic counts were independent predictors of pT stage (p = 0.0004 and 0.0001) and vascular invasion (p = 0.0004 and 0.0001). When tumors were separated on the basis of architectural and/or cytological atypia into "usual seminomas" and "seminomas with atypia", these were significantly associated with AJCC stage (p = 0.02), and c-kit protein (p = 0.0005) and CD30 expression (p = 0.02). In addition, "seminomas with atypia" also tended to show a higher proliferation activity as judged by Ki67 reactivity (p = 0.06), as well as express the marker of epithelial differentiation, Cam 5.2 (p = 0.09). In summary, we find that the morphologic features in testicular seminomas are associated with factors of clinical relevance. Also, "seminomas with atypia" differ from "usual seminomas" morphologically, present at a higher AJCC stage, and possibly represent an early step in transformation of seminomas toward a more aggressive phenotype. While not proposing a new entity, we suggest that when these atypical features are encountered in an otherwise classical seminoma, investigations must be performed to exclude an early carcinomatous differentiation or even earlier changes toward such a differentiation, such as lack of c-kit protein expression.

Topics: Adult; Biomarkers; Biomarkers, Tumor; Humans; Immunohistochemistry; Keratins; Ki-1 Antigen; Ki-67 Antigen; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Prognosis; Proto-Oncogene Proteins c-kit; Seminoma; Testicular Neoplasms

Topics: Actins; Desmin; Humans; Immunohistochemistry; In Situ Hybridization; Infant, Newborn; Karyotyping; Keratins; Male; Muscle, Smooth; Neoplasms, Gonadal Tissue; Receptors, Progesterone; S100 Proteins; Sertoli Cells; Testicular Neoplasms; Vimentin

The distinction of Sertoli cell tumors from seminoma is critical to ensure proper treatment. Although usually straightforward, we highlight herein 13 malignant Sertoli cell tumors of the testis with light microscopic features that mimicked seminoma. All of the cases were received in consultation, 10 with submitting diagnoses of seminoma, usually of classic type, but three cases of spermatocytic type. Patients ranged from 15 to 80 years of age (median 37 years); all presented with testicular masses. The tumors were typically firm, white to yellow-tan, and often had foci of hemorrhage. The dominant microscopic pattern was nested or sheet-like, with some tumors having secondary patterns of trabeculae-solid tubules, hollow tubules, and pseudofollicles. Tumor cells were polygonal with conspicuous clear cytoplasm in 12 cases; the cytoplasm was focally eosinophilic in 10 cases, but this was never conspicuous. Nine tumors had cytoplasmic vacuoles, and three of four that were investigated stained for intracytoplasmic glycogen. Nuclei were small (5) to medium-sized (8), round-to-oval (13), and vesicular with irregular contours (11). Nucleoli were present in 11 tumors (six small; five large). Stromal fibrosis (12) and lymphoid infiltrates (10) were conspicuous, and tumor necrosis (11) and vascular invasion (8) also were seen. Mitotic figures ranged from <1 to 21/10 high power fields (HPF) (median 1/10 HPF). Staining for inhibin-alpha, epithelial membrane antigen, and cytokeratin (AE1/AE3) was positive in four of four, six of six, and three of six cases, respectively; placental alkaline phosphatase was negative in all five tumors investigated. The nested growth pattern, prominence of clear cells, lymphoid infiltrate, inconspicuous tubular differentiation, cytoplasmic glycogen, and prominent nucleoli caused these tumors to be mistaken for seminomas. The smaller, less pleomorphic nuclei of Sertoli cell tumors, their lower mitotic rate, and the absence of intratubular germ cell neoplasia are helpful differential features. Immunohistochemistry is a useful adjunct in confirming the diagnosis of Sertoli cell tumor, but only if the overlapping features are appreciated by conventional microscopy and the diagnosis of Sertoli cell tumor included in the differential.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Inhibins; Keratins; Male; Middle Aged; Mucin-1; Neoplasm Proteins; Seminoma; Sertoli Cell Tumor; Testicular Neoplasms

The Sertoli-stromal cell tumor (SSCT) of the ovary shows a histologic resemblance to developing or adult testes and is often associated with virilization caused by tumor-produced androgenic hormone. In spite of the unique manifestation of SSCT, detailed characteristics of this tumor are still obscure. The mechanism by which SSCT occurs has not yet been determined. Six SSCTs were studied immunohistochemically, ultrastructurally, and by polymerase chain reaction (PCR) for the presence of sex-determining region Y (SRY) gene and the X chromosome activation state. Immunohistochemically, Sertoli-like cells of SSCT were positive not only for alpha-inhibin but also low-molecular-weight cytokeratin. In control testes, the expression of alpha-inhibin and cytokeratin was limited to a Sertoli cell component and rete testis, respectively. Ultrastructurally, tumor cells composing hollow tubules had an elongated nucleus with deep indentation and annulate lamellae, which are characteristic structures of mature Sertoli cells. In addition, they had studded microvilli on the apical surface and frequent desmosomes, which are structures noted in the cells of rete testis. Histologically, tumor cells of hollow tubules sometimes pouted into the lumen, as did the cells of tubulae rete, entrance into rete testis from seminiferous tubules. All of these findings indicate that some tumor cells of a SSCT show simultaneous differentiation into both Sertoli cells and cells of rete testis. SRY gene was not detected in any cases, and the X chromosome activation pattern was the same as that of the female control.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; DNA Primers; DNA-Binding Proteins; DNA, Neoplasm; Female; Humans; Immunoenzyme Techniques; Inhibins; Keratins; Male; Microsatellite Repeats; Nuclear Proteins; Ovarian Neoplasms; Polymerase Chain Reaction; Sex Cord-Gonadal Stromal Tumors; Sex Determination Analysis; Sex-Determining Region Y Protein; Testicular Neoplasms; Transcription Factors; X Chromosome

To investigate the histogenesis of paratesticular adenomatoid tumour by use of immunohistochemical markers for a variety of carcinomas and mesothelioma.. Immunohistochemical staining of sections from 12 cases of paratesticular adenomatoid tumour was undertaken using primary antibodies to antigens expressed by benign epithelial cells and carcinoma (cytokeratin AE1/AE3, cytokeratin 34ssE12, epithelial membrane antigen, MOC-31, Ber-EP4, CEA, B72.3, LEA.135, Leu M1), stromal and vascular markers (vimentin, CD34, factor VIII), and mesothelioma-associated antigens (thrombomodulin, HBME-1, OC 125) and p53 protein. There was absence of immunohistochemical expression of epithelial/carcinoma markers MOC-31, Ber-EP4, CEA, B72.3, LEA.135, Leu M1 and to factor VIII and CD34. All tumours expressed cytokeratin AE1/AE3, epithelial membrane antigen and vimentin, with weak expression of cytokeratin 34ssE12 in 25% of tumours. Each tumour showed expression of thrombomodulin, HBME-1 and OC 125 in a membranous distribution. p53 protein expression was not detected.. The immunohistochemical profile of paratesticular adenomatoid tumour is strongly supportive of a mesothelial cell origin.

Topics: Adenomatoid Tumor; Biomarkers, Tumor; CA-125 Antigen; Humans; Immunohistochemistry; Keratins; Male; Mesothelioma; Mucin-1; Testicular Neoplasms; Testis; Thrombomodulin; Vimentin

We studied cytokeratin (CK) expression immunohistochemically in 64 seminomas using a panel of commercially available antikeratin antibodies and tested for association of CK expression with patient age, tumor size, stage, and outcome. Seventeen embryonal carcinomas were compared with seminoma. CK7, CAM 5.2, AEI/AEIII, and wide-spectrum screening keratin (WSK) were positive in 41%, 30%, 36%, and 36% of the seminomas, respectively. CK20 and high-molecular-weight keratin (HMWK) were negative in all cases. CD30, placental alkaline phosphatase (PLAP), and epithelial membrane antigen (EMA) were positive in 6%, 100%, and 2% of cases, respectively. There were no differences in patient age, stage, tumor size, or outcome between CK-positive and CK-negative seminomas. CK7, CAM 5.2, AEI/AEIII, and WSK were positive in 100%, 88%, 94%, and 88% of embryonal carcinomas, respectively. CK20 and HMWK were negative in all cases. CD30, EMA, and PLAP were positive in 100%, 12%, and 76%, respectively. CKs are present in seminoma, and their presence is not associated with a difference in patient age, stage, or outcome. In cases such as small needle biopsy specimens, CK and CD30 stains may be useful in separating seminoma from embryonal carcinoma.

Topics: Adult; Aged; Alkaline Phosphatase; Carcinoma, Embryonal; Germinoma; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucin-1; Neoplasm Staging; Seminoma; Testicular Neoplasms

The clinicopathological, immunohistochemical and aetiological aspects, with respect to asbestos, of seven primary gonadal mesotheliomas (three intratesticular, four ovarian) are described and compared. These tumours are extremely rare, poorly described and the knowledge of their natural history is very limited.. The cases were collated from the UK Health and Safety Executive Mesothelioma Register over a 24-year period (1968-91). Primary mesotheliomas of the tunica vaginalis and ovary comprised 0. 09% (10 cases) and 0.03% (three cases) of mesothelioma deaths, respectively. No primary intratesticular (non-tunica vaginalis) malignant mesotheliomas have been described. In this study, we present seven (three intratesticular, four ovarian) primary malignant gonadal mesotheliomas. In both genders the tumours show a similar age distribution (with median onset in the sixth decade), a similar association with asbestos (in approximately 50% cases), a diverse histological spectrum (with predominantly tubulopapillary epithelial subtype tumours) and an immunophenotype that is comparable with malignant pleural and peritoneal mesothelioma. The clinical course appears variable (mean, 26 months; range, 9-50 months). All tumours in the study presented as localized masses and their prognosis appeared more favourable than that of diffuse pleural and peritoneal cases.. An awareness of the existence of these rare forms of malignant mesothelioma is important to prevent misdiagnosis. Immunohistochemistry has an important role in confirmation of the diagnosis. The accurate diagnosis of primary gonadal mesothelioma has potentially important medicolegal compensation considerations as a significant proportion of these cases are associated with asbestos.

Topics: Adult; Aged; Asbestos; Calbindin 2; Carcinogens; Fatal Outcome; Female; Humans; Hyaluronan Receptors; Immunohistochemistry; Keratins; Male; Mesothelioma; Middle Aged; Ovarian Neoplasms; S100 Calcium Binding Protein G; Testicular Neoplasms; Thrombomodulin

Based on immunohistochemistry (IHC) and DNA ploidy, different paths of carcinogenesis have been suggested for spermatocytic seminoma (SS) and classical seminoma (CS). The present study extends current knowledge on the above parameters.. Seventeen SSs and twenty-two CSs were assessed by IHC for placental-like alkaline phosphatase (PLAP), c-kit, cytokeratin and adhesion carbohydrate molecyles. All SSs and 11 CSs were also analysed for DNA ploidy.. All CSs, but none of the SSs, were positive for PLAP. C-kit positivity was found in 7 of 17 SSs and in all CSs. The other IHC parameters were similarly distributed among the evaluated SSs and CSs. Fourteen SSs were diploid or polyploid, and three were aneuploid. All CSs were aneuploid.. The new observation of c-kit positivity in about 40% of SSs suggests that at least some of the SSs originate from primordial cells. The predominantly diploid or polyploid DNA pattern indicates that SSs follow a pathogenetic pathway which is most probably different from that of CSs.

Topics: Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Aneuploidy; Cell Adhesion Molecules; Diploidy; DNA, Neoplasm; Flow Cytometry; Humans; Immunohistochemistry; Isoenzymes; Keratins; Male; Middle Aged; Ploidies; Polyploidy; Proto-Oncogene Proteins c-kit; Seminoma; Testicular Neoplasms

Desmoplastic small round-cell tumor typically occurs in the abdomen of young men, but it can also develop at other anatomic sites and in older people, presenting greater diagnostic difficulties. We report a case of this tumor arising from the paratesticular region in a 43-year-old man. The tumor showed histologic, immunohistochemical, and ultrastructural evidence of multilineage differentiation, including epithelial, mesenchymal, and neuronal features. In addition, the presence of an EWS and WT1 chimeric messenger RNA was demonstrated by the reverse transcriptase-polymerase chain reaction using an EWS exon 7 primer and WT1 exon 8 and exon 9 primers, which revealed single polymerase chain reaction products with a junction of EWS exon 7 to WT1 exon 8. Our study demonstrates that desmoplastic small round-cell tumors of the paratesticular region share not only morphologic but also molecular genetic features with those of the abdomen and that reverse transcriptase-polymerase chain reaction analysis using paraffin sections is useful for a conclusive diagnosis.

Topics: Abdominal Neoplasms; Adult; Base Sequence; Desmin; Diagnosis, Differential; Genitalia, Male; Humans; Immunohistochemistry; Keratins; Male; Molecular Sequence Data; Mucin-1; Neural Cell Adhesion Molecules; Oncogene Proteins, Fusion; Paraffin Embedding; Phosphopyruvate Hydratase; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Testicular Neoplasms; Vimentin

A case of tubular seminoma in a 33-year-old man is reported. The tumor occurred in his right testis, measuring 7 x 6 x 6 cm in size. Microscopically, most of the tumor cells were arranged in solid or hollow tubular patterns. The tumor cells had round nuclei with vesicular chromatin and clear or granular cytoplasm, characteristic features of seminoma cells. A classic seminoma component and intratubular atypical germ cells occupying approximately 5% of the tumor area were noted. Immunohistochemical staining revealed that the tumor cells were diffusely placental alkaline phosphatase and vimentin positive, and focally cytokeratin positive. These findings are consistent with a tubular seminoma. The differential diagnoses are discussed.

Topics: Adult; Alkaline Phosphatase; GPI-Linked Proteins; Humans; Immunohistochemistry; Isoenzymes; Keratins; Male; Seminoma; Testicular Neoplasms; Treatment Outcome; Vimentin

Cellular alkaline phosphatases (ALP) are increasingly recognised as important markers for monitoring tumour cell behaviour in human malignancies. Colorimetric, flow-cytometric, and immunocytochemical assays were employed to assess the influence of activation on expression of cellular ALP in human tumour cell lines. The results showed the following: (1) Testis tumour biopsies (16/16) unlike bladder (0/14) and head and neck (0/16) tumours showed positive staining for ALP, particularly the placental type, i.e. PLAP, although this was not always present on all the cells of non-seminoma biopsies. (2) The intensity of ALP expression differed widely in tumour cell lines. Based on biochemical analysis, the profile of ALP fell into two categories: (a) low expressing (MW 70 kD, placental type ALP) like Hep2 and KB lines, and (b) those expressing both low and high molecular (MW 95 kD) bands like testis lines Tera II and Ep2102. In all cases treatment of tumour cell lysates with heat prior to biochemical analysis showed the disappearance of the higher and sharpening of the lower molecular weight ALP band. (3) Exposure of tumour cells to epidermal growth factor (EGF) expressing EGF receptor led to a decreased ALP expression by as much as 54% as assessed by biochemical or flow-cytometric techniques. These data demonstrated that testis tumour tissues and cell lines expressed ALP which were different from others. The data also showed that exposure of tumour cell lines expressing EGFr to EGF resulted in suppression of ALP expression. These observations are consistent with the notion that EGFr and PLAP expression may be taken as a marker of proliferation and differentiation in human malignancies, respectively.

Topics: Alkaline Phosphatase; Biomarkers, Tumor; Blotting, Western; Electrophoresis; ErbB Receptors; Female; Flow Cytometry; Humans; Immunoenzyme Techniques; Isoenzymes; Keratins; Male; Testicular Neoplasms; Tumor Cells, Cultured

We have derived a clonal cell line (HGCT-1) from a lymph node metastasis of a primary testicular germ cell tumor (GCT). The tumor was negative for the embryonal carcinoma (EC) cell marker BerH2 but positive for vimentin, cytokeratin (CK) and desmin. Comparative genomic hybridization (CGH) revealed a high-level amplification at 12p that was observed in both the metastatic tumor and in the cultured HGCT-1 cells. In vitro, the phenotype of HGCT-1 cells was modulated by the culture conditions. In the presence of 10% fetal calf serum (FCS), the majority of HGCT-1 cells lacked CK and desmin. If cultured in 0.5% FCS, HGCT-1 cells acquired a uniform co-expression of vimentin, CK and desmin. Upon treatment with retinoic acid (RA), HGCT-1 cells lost the expression of desmin, but exhibited abundant CK filaments. Simultaneously, they started to express desmoplakin, form desmosomes and flatten on the culture substratum. The RA-induced changes were irreversible, whereas those following the culture in 0.5% FCS were at least partially reversible. When xenografted into an immunosuppressed rat, HGCT-1 cells formed a tumor consisting of epithelial- and mesenchymal-like structures. HGCT-1 cells thus represent a pluripotential cell system with a capacity for reversible phenotypic modulation and for irreversible differentiation into epithelial-type cells. The behavior of this novel cell line, distinct from established EC cell models, suggests a complex regulation of GCT cell differentiation.

Topics: Animals; Cell Culture Techniques; Cell Differentiation; Chromosome Aberrations; Clone Cells; Desmin; Germinoma; Humans; Immunohistochemistry; Immunosuppression Therapy; Keratins; Lymphatic Metastasis; Male; Mesoderm; Phenotype; Rats; Testicular Neoplasms; Transplantation, Heterologous; Tretinoin; Tumor Cells, Cultured; Vimentin

We investigated Sertoli cells in testicular biopsies with carcinoma in situ (CIS) in respect to cytokeratin expression to elucidate the status of Sertoli cell differentiation adjacent to CIS in human testes. Cytokeratin 18 intermediate filaments indicate a state of undifferentiation usually observed in Sertoli cells of prepubertal testes.. 29 testicular biopsies presenting CIS were investigated by means of immunohistochemistry, using a polyclonal antibody against placental-alkaline phosphatase to detect CIS cells and a monoclonal antibody against human cytokeratin 18 to show expression of cytokeratin 18 intermediate filaments in Sertoli cells.. All tubules bearing CIS showed positive cytokeratin expression of Sertoli cells if tubules were devoid of normal germ cells. However, a total of 13 specimen revealed CIS cells together with normal germ cells. In the presence of CIS cells together with round or elongated spermatids, adjacent Sertoli cells did not express cytokeratin immunoreactivity. In the case of combined presence of CIS and spermatogonia and primary spermatocytes, Sertoli cells could be found either immunopositive or immunonegative, and were positive in tubules with CIS and spermatogonia only.. Sertoli cells associated with CIS cells undergo a process of dedifferentiation, seen by the re-expression of cytokeratin intermediate filaments. We suggest that this dedifferentiation results in a loss of Sertoli cell function and leads to a cessation of spermatogenic activity.

Topics: Adolescent; Adult; Carcinoma in Situ; Cell Differentiation; Humans; Keratins; Male; Middle Aged; Sertoli Cells; Testicular Neoplasms

Testicular Sertoli cell tumours (SCT) and juvenile granulosa cell tumours (JGCT) are rare in childhood. This study was designed to investigate the clinical picture, morphology and disease course in a comparatively large series of cases (total number = 29). Of 198 cases of childhood testicular tumour documented in the Kiel Paediatric Tumour Registry 18 were cases of infantile SCT (9.1%) and 11 of JGCT (5.6%). The average age at the time of diagnosis was 4.2 months for infantile SCT and 0.4 months for IGCT. SCT and JGCT often showed infiltrative growth into adjacent testicular tissue, dense cellularity and considerable proliferation activity. Immunohistochemically all cases expressed vimentin intermediate filaments in both tumour types. Next in frequency of expression were cytokeratins (SCT: 7/16; JGCT: 7/10) and smooth-muscle actin (SCT: 9/15; JGCT: 4/10). Follow-up studies (24/29) showed that in cases of tumour manifestation in infancy and after complete tumour removal (usually orchiectomy) no local recurrences and no metastases occurred. The most important conclusion for diagnosis and therapy is that despite infiltrative growth, incomplete differentiation, dense cellularity and considerable proliferation activity, after surgical excision infantile SCT and JGCT have a good prognosis. Adjuvant chemotherapy or more extensive operations with lymphadenectomy are thus not indicated.

Topics: Actins; Adolescent; Biomarkers; Cell Division; Child; Child, Preschool; Female; Follow-Up Studies; Granulosa Cells; Humans; Immunohistochemistry; Infant; Infant, Newborn; Keratins; Male; Sertoli Cells; Testicular Neoplasms; Vimentin

Intratesticular Müllerian papillary serous tumors lacking stromal invasion are uncommon neoplasms whose immunophenotypic properties have not been studied extensively. We present such information here and compare it with information from a group of ovarian papillary serous tumors of low malignant potential ("borderline serous tumors") that are morphologically identical. We compared the histologic features of our index case of intratesticular Müllerian papillary serous tumor with those of nine ovarian papillary serous tumors. We then evaluated both the index case and the ovarian tumors with antibodies against carcinoembryonic antigen, LeuM1, CA125, estrogen receptors, progesterone receptors, cytokeratin 7, and cytokeratin 20, by use of established immunohistochemical techniques. The testicular and ovarian tumors were morphologically indistinguishable. The intratesticular Müllerian papillary serous tumor expressed LeuM1, CA125, estrogen receptors, progesterone receptors, cytokeratin 7, and weak cytokeratin 20; carcinoembryonic antigen was not expressed. All of the ovarian papillary serous tumors expressed CA125, estrogen receptors, and cytokeratin 7. Eight of nine expressed progesterone receptors. Five of nine stained with LeuM1. Two of nine were focally weakly positive with cytokeratin 20. LeuM1 expression helps distinguish testicular papillary serous tumors from mesothelial proliferations, which might seem morphologically similar. The immunophenotype of intratesticular and female genital papillary serous tumors is similar; this similarity extends to expression of estrogen and progesterone receptors, which is rare in neoplasms in men, especially among testicular neoplasms.

Topics: Aged; Biomarkers; CA-125 Antigen; Cystadenocarcinoma, Papillary; Female; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Lewis X Antigen; Male; Orchiectomy; Ovarian Neoplasms; Receptors, Estrogen; Retrospective Studies; Testicular Neoplasms

Unclassified sex cord-stromal tumors (SCSTs) of the testis comprised predominantly of spindle cells can be difficult to classify. To achieve better definition of these tumors, we examined the histologic, histochemical, and ultrastructural features of four unclassified SCSTs with spindle-cell features, and compared their immunohistochemical features with those of 24 other SCSTs of the testis and ovary. Three of the spindle-cell tumors were composed of relatively short spindled cells with prominent nuclear grooves and intermixed epithelioid cells. All of the three were located adjacent to the rete testis. The fourth case consisted of elongate spindle cells that were reminiscent of smooth muscle. In all of the four cases, reticulin enveloped aggregates of cells of various sizes but not individual cells. Ultrastructural analysis of two of the spindle-cell tumors revealed desmosomes, numerous thin filaments, and focal dense-bodies. Immunohistochemically, all of the four tumors were reactive for S-100 protein and smooth muscle actin. Staining for S-100 protein and smooth muscle actin was also observed in three of six granulosa cell tumors and both juvenile granulosa cell tumors. Although variable staining for S-100 protein was found in 5 of the 12 other SCSTs (4 Leydig cell, 6 Sertoli-Leydig cell, and 2 unclassifiable ovarian SCSTs), reactivity for smooth muscle actin was present in only 1 Sertoli-Leydig cell tumor. In contrast, all of the four ovarian fibromas/thecomas were reactive for smooth muscle actin but failed to stain for S-100 protein. Taken together, the histologic, histochemical, immunohistochemical, and ultrastructural features of the spindle-cell tumors are similar to those of granulosa cell tumors. Reactivity for S-100 protein and smooth muscle actin is characteristic of these tumors. These tumors should be distinguished from other unclassified SCSTs.

Topics: Actins; Adult; Female; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Ovarian Neoplasms; S100 Proteins; Sex Cord-Gonadal Stromal Tumors; Testicular Neoplasms

We evaluated the presence of human chorionic gonadotropin (hCG), alpha-fetoprotein (AFP) and a panel of other tumor markers in the compartment next to the tumor (that is, the malignant hydrocele fluid).. We measured hCG, AFP, neuron-specific enolase, carcinoembryonic antigen and cytokeratin-19 fragments in cubital vein sera and in hydrocele fluids of patients with testicular cancer. Results were compared with those obtained from hydrocele fluids of patients with benign disease.. All tumor markers remained under the respective cutoff values in benign hydroceles. In patients with pure seminomas, hCG levels were elevated in 66% of hydroceles but only once in peripheral sera, whereas AFP remained low in both compartments. Furthermore, of 11 cases of nonseminomatous germ cell tumor hydrocele fluids, 3 with negative peripheral tumor marker values had to be reclassified marker positive, of which 2 showed elevated hCG levels and 1 had increased levels of AFP. Significant changes of neuron-specific enolase and carcinoembryonic antigen concentrations could not be observed. However, a cytokeratin-19 fragment measured by Cyfra 21-1 assay was elevated in 2 of 3 seminomatous and in 4 of 8 nonseminomatous hydroceles.. These data give a new insight into the in vivo secretion pattern of testicular germ cell neoplasms, which demonstrates that the term "marker negative" should be restricted to selected cases of testicular cancer. Analysis of tumor markers in hydrocele fluids may be a helpful tool in patients with scrotal swelling if clinical and sonographic results remain uncertain.

Topics: Adolescent; Adult; Aged; alpha-Fetoproteins; Biomarkers, Tumor; Body Fluids; Child; Child, Preschool; Chorionic Gonadotropin; Germinoma; Humans; Keratins; Male; Middle Aged; Scrotum; Testicular Hydrocele; Testicular Neoplasms

Primary choriocarcinoma of the anterior mediastinum is by far the rarest and most controversial form of extragonadal germ cell tumor. A clinicopathologic study of eight primary mediastinal neoplasms bearing the histopathologic and immunohistochemical features of choriocarcinoma is presented. The patients were all men between the ages of 21 and 63 years (mean, 42 years). Clinical symptoms included shortness of breath, chest pain, cough, and superior vena cava syndrome; one patient also had gynecomastia. All patients presented with large anterior mediastinal masses on chest radiographs that measured an average of 10 cm in greatest diameter. Grossly, the tumors were described as large, soft, extensively hemorrhagic, and with foci of necrosis. Histologically, they were characterized by a dual cell population composed of cytotrophoblastic cells with uniform, round nuclei, clear cytoplasm, and prominent nucleoli admixed with large, multinucleated syncytiotrophoblastic cells with bizarre nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm. Immunohistochemically, the tumors were notable for strong keratin and beta-human chorionic gonadotropin (HCG) positivity. Seven patients presented at the time of diagnosis with thoracic and extrathoracic (liver, adrenal, kidney, and spleen) metastases. In one case, the tumor was entirely confined to the mediastinum. All patients died over a period of 1 to 2 months. Complete autopsies were performed in all cases; none of the patients showed evidence of a testicular tumor or scar after thorough examination of the testes on serial sectioning. The present cases demonstrate the widespread distribution of germ cells in the human body and lend further support to the existence of primary extragonadal choriocarcinoma arising in the thymic region.

Topics: Adrenal Gland Neoplasms; Adult; Alkaline Phosphatase; alpha-Fetoproteins; Biomarkers, Tumor; Carcinoembryonic Antigen; Choriocarcinoma; Chorionic Gonadotropin; Diagnosis, Differential; Humans; Immunohistochemistry; Isoenzymes; Keratins; Kidney Neoplasms; Liver Neoplasms; Male; Mediastinal Neoplasms; Middle Aged; Placental Lactogen; Splenic Neoplasms; Testicular Neoplasms

NCR-G3 cells were established from a testicular embryonal carcinoma and are highly multipotential, differentiating into trophectoderm cells upon exposure to retinoic acid. Differentiated NCR-G3 cells begin to produce human chorionic gonadotropin (hCG), a trophectoderm-specific hormone. We have previously isolated the up-regulated genes at the early stage of differentiation. One of them was found to be a heat shock protein gene. The heat shock protein gene (HSP90) is induced at the early stage of differentiation and decreases to the basal level or under the basal level at the later stage. We speculate that heat shock per se induces the differentiation of human EC cells. With exposure to heat, NCR-G3 cells began to express a series of differentiation markers such as cytokeratin and hCG. Heat, which is classically known to induce heat shock proteins, is able to differentiate an embryonal cell line into trophectoderm lineages, implying a new recognized function of a heat-like event in early differentiation.

Topics: Carcinoma, Embryonal; Cell Differentiation; Chorionic Gonadotropin; Ectoderm; Gene Expression Regulation, Developmental; Heat-Shock Response; HSP90 Heat-Shock Proteins; Humans; Immunohistochemistry; Keratins; Male; Testicular Neoplasms; Tretinoin; Trophoblasts; Tumor Cells, Cultured

The intermediate filament of mature human Sertoli cells is vimentin. A co-expression of vimentin together with cytokeratin has been demonstrated in Sertoli cells during embryonal development and under pathologic conditions in adult testes. We analysed the presence of vimentin, cytokeratin, and desmin in Sertoli cells of fetal testes (n=20), in seminiferous tubules of cryptorchid testes (n=10) and adjacent to testicular germ cell tumours (n=47) using specific monoclonal antibodies and single and double-labelling immunohistochemistry. During embryonal development prominent cytokeratin expression disappears after the 20th week of gestation. Interestingly, we also found desmin in immature intratubular Sertoli cells between weeks 11 and 14. In adult cryptorchid testes and in peritumour tubules, desmin was also prominently present in Sertoli cells in the vast majority of the cases investigated, as well as vimentin and cytokeratin co-expression. This first description of desmin immunoreactivity may shed some light on the ontogeny of human Sertoli cells and demonstrates that this cell type is able to express three types of intermediate filaments in a complex manner.

Topics: Adult; Cryptorchidism; Desmin; Female; Fetus; Humans; Infant, Newborn; Intermediate Filament Proteins; Keratins; Male; Pregnancy; Sertoli Cells; Testicular Neoplasms; Testis; Vimentin

We describe the cytohistological, immunohistochemical and ultrastructural findings in a 55-yr-old-man with history of asbestos exposure and diffuse malignant mesothelioma (DMM) of the pleura, peritoneum, and tunica vaginalis presenting with chest pain and scrotal swelling. Pleural fine-needle aspiration (FNA) revealed mesenchymal elements and spindle-shaped epithelial-like cells, while biopsy showed pure sarcomatous tumor invading lung parenchymal. In both samples tumor cells coexpressed cytokeratin and vimentin. Peritoneal and hydrocele effusions contained aggregates of malignant mesothelial cells. Electron microscopy showed intermediate filaments, rare desmosomes and sparse microvilli. Morphological findings were consistent with a DMM, with a biphasic pattern in the pleura and an epithelial one in the peritoneum and tunica vaginalis. Although the possibility of a multicentric origin cannot be ruled out, clinical chronologic sequence suggests that the pleura was the primary involved site, followed by spread to peritoneum and tunica vaginalis.

Topics: Asbestos; Biopsy, Needle; Humans; Immunohistochemistry; Keratins; Male; Mesothelioma; Microscopy, Electron; Middle Aged; Neoplasms, Multiple Primary; Occupational Diseases; Peritoneal Neoplasms; Pleural Neoplasms; Testicular Neoplasms; Tomography, X-Ray Computed; Vimentin

In testicular germ cell tumors the CD30 antigen has been shown to be regularly expressed in embryonal carcinoma and was thus suggested as a marker for this particular neoplasm. Very recently, it has been proven that the monoclonal antibody Ber-H2 is suitable for the detection of this membrane antigen in paraffin sections. We conducted an immunohistochemical study to investigate the CD30 expression in a large series of different presentations of seminoma (ie, pure, mixed, and spermatocytic) because there is evidence from several sources that embryonal carcinoma is histogenetically closely related to, and probably derives from, seminoma. Sections from formalin-fixed, paraffin-embedded tissue from 38 cases of testicular seminomas were immunostained for the demonstration of the CD30 antigen using the monoclonal antibody Ber-H2, cytokeratins, and placental alkaline phosphatase following an indirect streptavidin-peroxidase regimen. In selected cases, immunostainings were performed on consecutive sections to investigate a possible colocalization of CD30 and cytokeratins in seminoma. Specific immunostaining for CD30 in seminoma cells could be detected in single minute foci in 4 of 21 cases of pure classic seminoma. Seminomatous components of mixed tumors showed CD30 positivity in single, but also multiple, foci in 7 of 14 cases. CD30 immunoreactivity in seminoma cells occurred with and without colocalized expression of cytokeratin. Spermatocytic seminoma (n = 3) as well as intratubular germ cell neoplasia in tumor adjacent parenchyma (n = 36) were negative in all cases investigated. We conclude that in testicular germ cell tumors, the expression of CD30 is not restricted to embryonal carcinoma but can also be found focally in seminoma, adding further evidence for a close relationship between these two tumors. The prevalence of CD30 expression in seminomatous components of mixed tumors, as well as the coexpression with cytokeratins, suggest that CD30 expression in seminomas might indicate their upcoming transformation to embryonal carcinoma. This conclusion coincides with a model featuring seminoma in a central role of germ cell tumor development.

Topics: Adolescent; Adult; Aged; Alkaline Phosphatase; Biomarkers, Tumor; Carcinoma, Embryonal; Humans; Immunohistochemistry; Keratins; Ki-1 Antigen; Male; Middle Aged; Seminoma; Testicular Neoplasms

Five cases of large cell calcifying Sertoli cell tumour of the testis not associated with complex dysplastic syndromes are reported. The age of the patients ranged from 13 to 34 years and all the tumours were histologically similar, having large, isomorphic, non-mitotic, eosinophilic Sertoli cells with foci of calcification. Flow cytometry demonstrated the cells to be diploid or hypodiploid. All cases were positive for vimentin and focally positive for low molecular weight keratin. The present cases, together with a review of the 22 previously reported tumours, demonstrate that there are two clear cut types of large cell calcifying Sertoli cell tumour; those which are associated with complex dysplastic syndromes and which are bilateral and multifocal, and those which are not associated and are unilateral and focal. Prognosis in all of our cases was uniformly good despite invasion of the rete testis in two cases. It is considered that conservative resection of the tumour is the treatment of choice in cases not associated with complex dysplastic syndromes, since the malignancy rate is low.

Topics: Adolescent; Adult; Calcinosis; Diagnosis, Differential; Flow Cytometry; Humans; Immunohistochemistry; Keratins; Male; Sertoli Cell Tumor; Testicular Neoplasms; Ultrasonography; Vimentin

In the light of a case report, the authors recall the clinical signs of adenocarcinoma of the rete testis and the precise histological and immunohistochemical features allowing confirmation of this very rare diagnosis. They emphasize the persistent controversies concerning the treatment of this testicular tumour.

Topics: Adenocarcinoma, Papillary; Aged; Epididymis; Humans; Immunohistochemistry; Keratins; Male; Seminiferous Tubules; Spermatic Cord; Testicular Neoplasms

Intratubular germ cell neoplasia (ITGCN) is now considered to be the preinvasive phase of testicular germ cell tumors with the exceptions of spermatocytic seminoma, pure yolk sac tumor, and mature teratoma. Pagetoid spread of ITGGN into rete testis is a common yet unpublished finding in these cases. We reviewed 100 cases of testicular germ cell tumors from the Surgical Pathology service of Parkland Memorial Hospital (Dallas, TX) to evaluate the frequency of this pattern of spread. Additional sections were obtained from selected cases and were stained with anti-placental alkaline phosphatase, anti-low molecular weight keratin (clone AE1), and various lectins to highlight the process. Pagetoid spread of ITGCN into rete testis was identified in 24 of 60 cases (40%) in which histologic sections contained both ITGCN and rete testis. The incidence of pagetoid ITGCN involvement of the rete testis was lower in pure seminoma (seven of 25 cases [28%]) than in testes containing nonseminomatous germ cell tumors (17 of 35 cases [49%]). AE1 stained the epithelial cells of the rete testis but not the cells of the ITGCN, whereas placental alkaline phosphatase stained the neoplastic cells but not the epithelial cells of the rete testis. These stains were useful in delineating two cases in which the pagetoid involvement was so extensive that they were misdiagnosed as invasive seminomas. Pagetoid spread of ITGCN is a relatively common finding in testicular germ cell tumors and rarely can be mistaken for invasive seminoma. Immunohistochemistry can be helpful in distinguishing florid pagetoid spread from invasive seminoma.

Topics: Adolescent; Adult; Alkaline Phosphatase; Carcinoma in Situ; Cell Transformation, Neoplastic; Diagnosis, Differential; Epithelium; Germinoma; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Orchiectomy; Paget Disease, Extramammary; Seminoma; Testicular Neoplasms

The object of this study was to determine whether the immunohistochemical detection of cytokeratin (CK)-positive cells is useful as quick section diagnosis, and whether the retroperitoneal lymphadenectomy (RLA) can be reduced by this method without any disadvantage for the patient. The RLA represents a combined diagnostic and therapeutic procedure for staging as well as removal of regional lymph node metastases in patients with malignant testis tumors. The disadvantage of the radical RLA is a 40 to 90% loss of potency. The risk of the reduced RLA is the relapse. The metastatic affection of the first retroperitoneal lymph node station, the so-called "sentinale" lymph nodes, allows a judgement for the remaining lymph nodes, and, therefore, for the extent of the necessary operation. The conventional frozen technique has a limited reliability, whereas the paraffin technique needs too much time. We used the immunohistochemistry as alternative method for the rapid as well as reliable evaluation of metastases. A group (7 cases) of 35 patients with non-seminomatous tumors of the testis was only treated by radical RLA after detection of CK-positive cells in the sentinale lymph nodes. The other patients were treated by modified RLA (20 cases) or reduced RLA (6 cases). The results were compared with a control group (48 cases) which was treated by radical RLA only. Using the modified RLA the relapse-free interval was not affected and the loss of ejaculation as a consequence of radical treatment could be avoided.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Erectile Dysfunction; Fluorescent Antibody Technique; Humans; Intraoperative Period; Keratins; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Neoplasm Recurrence, Local; Retroperitoneal Space; Testicular Neoplasms

Topics: Adult; Carcinoembryonic Antigen; Cystadenoma; Epididymis; Humans; Immunohistochemistry; Keratins; Lectins; Male; Membrane Glycoproteins; Mucin-1; Plant Lectins; S100 Proteins; Testicular Neoplasms; Vimentin

Recent ultrastructural, cytogenetic, and ploidy analyses indicate that seminoma acts as a precursor from which other forms of testicular germ cell tumor may originate. Ten cases of primary or metastatic testicular germ cell tumors were investigated that showed possible transformation of seminoma to yolk sac tumor. Such transformation was identified in six cases in which foci of abrupt change from seminoma to various patterns of yolk sac tumor occurred, often at the periphery of otherwise pure lobules of seminoma. Immunostains for cytokeratins, placental-like alkaline phosphatase, and alpha-fetoprotein demonstrated the expected changes in reactivity at the foci of such transformation. Four additional cases were regarded as either seminomas with artifactual microcystic change or the close association of seminoma and yolk sac tumor but lacking evidence for transformation. These data support the theory that seminoma is not an "endpoint" neoplasm but may serve a precursor role in the progression to nonseminomatous germ cell tumors.

Topics: Adolescent; Adult; Alkaline Phosphatase; alpha-Fetoproteins; Biomarkers, Tumor; Cell Transformation, Neoplastic; Dysgerminoma; Humans; Immunohistochemistry; Isoenzymes; Keratins; Male; Mesonephroma; Middle Aged; Testicular Neoplasms

We have studied immunolocalization of all steroidogenic enzyme involved in sex steroids biosynthesis, P-450 side chain cleavage (P-450scc), 3 beta hydroxy steroid dehydrogenase (3 beta-HSD), P-450 17 alpha hydroxylase (P-450(17 alpha)) and P-450 aromatase (P-450arom) and that of vimentin and cytokeratin in 14 cases of testicular sex cord-stromal tumours (6 Leydig cell tumours, 5 Sertoli cell tumours, 2 fibromas and 1 granulosa cell tumour) as well as 4 cases of hyperplasia (2 Leydig and 2 Sertoli). Leydig cell tumour expressed all four steroidogenic enzymes examined, indicating that this tumour can synthesize oestrogen from cholesterol. In 2 cases of Sertoli cell tumour, the tumour cells with clear cytoplasm and without Reinke's crystals expressed P-450ssc, 3 beta-HSD and P-450(17 alpha), suggesting the capability of androgen production in these tumour cells. Fibromas and granulosa cell tumour were negative for the enzymes examined. In immunohistochemistry of intermediate filaments, Leydig cell tumours demonstrated only vimentin. Sertoli cells in hyperplasia and non-neoplastic testis expressed only vimentin but Sertoli cell tumours expressed both cytokeratin and vimentin. Cytokeratin immunoreactivity was correlated with morphological epithelial differentiation in Sertoli cell tumour. These findings in testicular Sertoli cell tumour are considered to represent the multiple differentiation capacity of this neoplasm. Immunohistochemical study of steroidogenic enzymes and intermediate filaments provided new insight into neoplastic steroidogenesis and the differentiation capacity of testicular sex cord-stromal neoplasms.

Topics: 3-Hydroxysteroid Dehydrogenases; Adolescent; Adult; Aged; Aromatase; Child; Child, Preschool; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Leydig Cell Tumor; Male; Middle Aged; Sertoli Cell Tumor; Steroid 17-alpha-Hydroxylase; Testicular Neoplasms; Vimentin

The presence of eosinophilic, hyaline globules in association with epithelial hyperplasia was noted in the rete testis of three patients with germ cell tumors. In the more florid examples, this proliferation formed a solid and microcystic pattern that, in association with the hyaline globules, mimicked a yolk sac tumor component. However, the bland cytologic features of the cells and the conformation to the configuration of the rete testis were keys to its reactive nature. A subsequent review of 48 testicular specimens containing well-defined areas of the rete testis showed hyaline globule formation in the rete testis or tubuli recti in 16 of 27 germ cell tumors, one of five other testicular tumors (four stromal tumors and one plasmacytoma), and none of 16 nonneoplastic cases. Many of the cases that had hyaline globules also showed epithelial hyperplasia. Further analysis demonstrated an incidence of rete testis invasion by neoplasm in cases that had hyaline globules, with or without epithelial hyperplasia, that was significantly higher (p less than 0.01) than that seen in neoplastic cases lacking hyaline globules. We concluded that this pseudoneoplastic reaction developed secondary to invasion of the rete testis by tumor. Immunostains supported the nonneoplastic nature of the proliferative lesions and indicated that the globules represented various proteins that had been absorbed from the lumen of the rete testis by the epithelial-lining cells but not successfully secreted.

Topics: Albumins; alpha 1-Antitrypsin; Diagnosis, Differential; Epithelium; Humans; Hyalin; Hyperplasia; Immunohistochemistry; Keratins; Lactalbumin; Male; Mesonephroma; Rete Testis; Testicular Neoplasms; Vimentin

A total of 113 patients with carcinomas of breast, testis, stomach and colon were examined for lymph node metastases by means of an exact case-by-case comparison by conventional histology and by immunohistochemistry using the anticytokeratin monoclonal antibody A45-B/B3. Among 891 examined lymph nodes, 90% of metastases were recognized by both methods, about 2% by histology alone, and more than 10% by immunohistochemistry alone. The method can be applied for intraoperative frozen section diagnosis.

Topics: Breast Neoplasms; Colonic Neoplasms; Female; Frozen Sections; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Paraffin; Stomach Neoplasms; Testicular Neoplasms

Topics: Cell Transformation, Neoplastic; Dysgerminoma; Humans; Keratins; Male; Testicular Neoplasms

During a routine long-term drug safety study, lasting approximately 2 1/2 yr, male Wistar rats, treated with a prolactin-inhibiting compound, developed an excess of Leydig cell tumors (LCTs). Most tumors were typical for the rat but a small number showed an unusual variation and some appeared malignant. The variation consisted of glandular and/or tubular structures within the tumor mass which occasionally anastomosed and contained an eosinophilic periodic-acid Schiff (PAS) positive material. In a few of these variants, malignant features such as cellular atypia, capsular, and lymphatic invasion and necrosis were seen. No metastases were detected. Detailed morphological and immunohistochemical investigations were conducted in order to establish the cell of origin of these variants. Glandular/tubular structures were found to stain with varying intensity for vimentin and cytokeratin, but were always negative for beta-tubulin. The results indicated that the cell of origin of these LCT variants was indeed the Leydig cell and that glandular and/or tubular structures within LCTs represented a form of Leydig cell metaplasia.

Topics: Animals; Antibodies; Cell Transformation, Neoplastic; Enkephalin, Methionine; Epitopes; Glial Fibrillary Acidic Protein; Immunohistochemistry; Keratins; Leydig Cell Tumor; Male; Phosphopyruvate Hydratase; Rats; Rats, Inbred Strains; S100 Proteins; Sertoli Cells; Substance P; Synaptophysin; Testicular Neoplasms; Tubulin

Observations differ on the pre-invasive malignant lesions associated with the various categories of testicular germ cell tumours. Such lesions have been found to be similar in appearance and are assumed to be composed of multipotent cells, or conversely a distinctive pre-invasive stage has been reported in association with each form of germ cell neoplasm. This study was undertaken to see whether distinctive morphological and immunohistochemical features of carcinoma in situ adjacent to various categories of germ cell tumours could be established. Carcinoma in situ adjacent to seminomas, teratomas and mixed germ cell tumours in 18 adults was indistinguishable morphologically. Placental alkaline phosphatase was demonstrated immunohistochemically but vimentin and low molecular weight cytokeratins were uniformly absent in these abnormal germ cells from all three groups. These findings support the concept of a multipotent pre-invasive malignant cell for both seminoma and teratoma in the adult. Carcinoma in situ was not seen adjacent to 15 spermatocytic seminomas, nor was placental alkaline phosphatase demonstrated in tubules adjacent to these tumours. These negative findings are additional evidence that spermatocytic seminoma differs from classical seminoma in its histogenesis. Carcinoma in situ, as defined morphologically and immunohistochemically in adults, was not identified adjacent to yolk sac tumours and differentiated teratomas in 20 prepubertal testes. The possibility that pre-invasive malignancy in children may not resemble that in adults must be considered when assessing the malignant potential of cryptorchid testes on biopsies taken during orchidopexy.

Topics: Adult; Alkaline Phosphatase; Antibodies, Monoclonal; Carcinoma in Situ; Child, Preschool; Dysgerminoma; Humans; Infant; Keratins; Male; Mesonephroma; Retrospective Studies; Sertoli Cells; Spermatogonia; Teratoma; Testicular Neoplasms; Vimentin

The patterns of cytoskeletal differentiation were studied in 20 testicular non-seminomatous germ cell tumors by immunohistochemistry, using diverse monoclonal antibodies specific for different intermediate filament (IF) proteins and for desmoplakin. Immunofluorescence and immunoperoxidase methods on both formalin-fixed and frozen tissues were applied, in some cases together with a gel electrophoretic analysis of IF proteins. The tumors examined included embryonal carcinoma (EC), endodermal sinus tumor (EST), choriocarcinoma and teratoma. Nine of the tumors were composed of only one histological type, the others showed mixed components. Cytokeratins 8 and 18 were identified in all these neoplasms, but their immunostaining was weak in ECs. Cytokeratin 19 was absent or very scarce in ECs, but strongly expressed in ESTs, choriocarcinomas and teratomas, thus allowing the identification of small EST and choriocarcinoma elements in ECs even when they were morphologically not obvious. Occasionally, some cells in ECs and ESTs also stained for cytokeratins 4 and/or 17, indicating potential for epithelial stratification. The majority of the germ cell tumors showed varied amounts of vimentin, often in co-existence with cytokeratins. Neurofilaments were demonstrated in scattered tumor cells in a single case of EST. In the teratomas studied, each type of tissue component present showed the expected IF protein. However, in many germ cell tumors some stromal cells and blood vessels contained, in addition to vimentin and desmin, also cytokeratins 8 and 18. This heterogeneity of the cytoskeletal profile of germ cell tumors is indicative of the varied differentiation potential inherent in these neoplasms.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Cell Differentiation; Choriocarcinoma; Desmosomes; Electrophoresis, Gel, Two-Dimensional; Fluorescent Antibody Technique; Humans; Intermediate Filament Proteins; Keratins; Male; Mesonephroma; Teratoma; Testicular Neoplasms

Human testicular germ cell tumors were studied immunohistochemically with the monoclonal antibody to the 54-kd keratin polypeptide (keratin 7) to determine whether this antibody could be used selectively to identify trophoblastic cells. The antibody reacted with the intermediate filaments in the cytoplasm of some cells in choriocarcinoma cell lines, and in trophoblastic cells in mixed germ cell tumors and a seminoma. It did not react with classic seminoma cells, embryonal carcinoma, yolk sac carcinoma, or somatic tissues of mixed germ cell tumors. On the basis of these data we conclude that monoclonal antibody to keratin 7 is a marker for a subset of trophoblastic cells in human germ cell tumors.

Topics: Adult; Biomarkers, Tumor; Dysgerminoma; Humans; Keratins; Male; Middle Aged; Neoplasms, Germ Cell and Embryonal; Testicular Neoplasms; Trophoblasts

Testicular seminoma has in the past been considered to represent a germ cell tumor incapable of further differentiation. In recent years this view has been challenged on the basis of morphologic and chromosomal studies. Moreover, studies of intermediate filaments (IF) of seminoma cells have provided evidence of the capability of seminoma cells to differentiate in different directions. In the present study of the IF protein profile of 26 human testicular seminomas, using frozen as well as formalin-fixed, paraffin-embedded tissues, we report evidence of a heterogeneous differentiation potential inherent in these neoplasms. Thus, in 4 of the seminomas neither cytokeratins nor vimentin were detected; 3 showed vimentin positive cells but no cytokeratins; in 4 seminomas only cytokeratins were detected. In the remaining 15 cases both cytokeratins and vimentin were present, with occasional cells demonstrating coexpression of cytokeratin and vimentin. While the cytokeratins present were mostly of the "simple epithelial type", in 2 instances seminoma cells also contained cytokeratins 4 and 17, normally found in stratified and/or complex glandular epithelia. Furthermore, in 3 cases scattered tumor cells stained for desmin and in 2 other seminomas neurofilaments were identified. All of the cases showed variable positive staining for desmoplakins and desmoglein, indicative of the presence of desmosomes. It can therefore be concluded that, while some seminomas seem to be devoid of IFs, most of them show varied differentiation patterns usually with epithelial features but occasionally also with components commonly regarded as characteristic of myogenic or neurogenic differentiation. These observations may help to elucidate the relationship of seminomas to other germ cell tumors, and also contribute to our understanding of the histogenesis of these neoplasms.

Topics: Desmin; Dysgerminoma; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Male; Microscopy, Fluorescence; Testicular Neoplasms

Testicular Leydig cell tumours are able to produce oestrogens and can be induced by exogeneous oestrogen administration. Oestrogen and progesterone receptors, cytokeratin, vimentin, and proliferative activity were determined immunohistologically in human testes in six Leydig cell tumours, 14 cases of Leydig cell hyperplasia, and 13 cases with normal Leydig cells. While both steroid receptors were detected in about 70 per cent of the tumour cells in cryostat sections, no reaction was observed in normal Leydig cells. This supports the hypothesis of an enhanced receptor state in a Leydig cell subpopulation as a basic pathophysiological factor in the development of Leydig cell tumours. On cryostat sections, all tumours co-express cytokeratin and vimentin. Neither the receptors nor the intermediate filaments could be detected reliably in paraffin sections. The low proliferative activity of Leydig cell tumours corresponds to their benign clinical course.

Topics: Adult; Aged; Antibodies, Monoclonal; Cytoskeleton; Humans; Hyperplasia; Intermediate Filaments; Keratins; Leydig Cell Tumor; Leydig Cells; Male; Middle Aged; Receptors, Estrogen; Receptors, Progesterone; Testicular Neoplasms; Vimentin

Small cell carcinoma of the ovary is a rare, poorly understood aggressive tumor of young women, associated with paraendocrine hypercalcemia in two-thirds of the cases. Immunohistochemical staining of 15 small cell carcinomas, one-third of which were associated with hypercalcemia, 15 adult granulosa cell tumors, 15 juvenile granulosa cell tumors, and 5 Sertoli cell tumors, was performed with the use of antibodies against cytokeratins (AE-1/AE-3, CAM 5.2, 902), epithelial tumor-associated antigens (B72.3, epithelial membrane antigen [EMA]), vimentin, S-100, neuron-specific enolase (NSE), lysozyme, parathyroid hormone, and chromogranin-A in an attempt to define histogenetically this tumor type. One-third of the small cell carcinomas were positive for EMA, whereas all of them were negative for B72.3 and S-100. In contrast, one-third of the granulosa cell tumors were positive for S-100 and all of them were negative for EMA and B72.3. One of five Sertoli cell tumors were positive for EMA and two were positive for B72.3, but all were negative for S-100. Differences existed in the frequency, intensity, and/or pattern of staining for cytokeratin, vimentin, lysozyme, and NSE among the various tumor types. A single small cell carcinoma from a patient with hypercalcemia stained focally for parathyroid hormone, whereas all 30 granulosa cell tumors and 4 of 5 Sertoli cell tumors were nonreactive. Chromogranin-A staining was noted in four of five small cell carcinomas, none of ten granulosa cell tumors, and two of five Sertoli cell tumors. These immunohistochemical findings, as well as previous light and electron microscopic data, do not clearly indicate any specific cell as the cell of origin of the ovarian small cell carcinoma.

Topics: Adult; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Small Cell; Chromogranin A; Chromogranins; Female; Granulosa Cell Tumor; Humans; Immunoenzyme Techniques; Keratins; Male; Membrane Glycoproteins; Mucin-1; Ovarian Neoplasms; S100 Proteins; Sertoli Cell Tumor; Testicular Neoplasms; Vimentin

Germ cell neoplasms were reviewed for the investigation of a mesenchyme-like component of yolk sac tumor (YST) characterized by spindle cells with few mitoses in a myxoid, vascular background. Nineteen YSTs with this pattern were identified. The mesenchyme-like component of these YSTs appeared to derive from the epithelial elements of YST, since cytokeratin as well as vimentin positivity occurred in the spindle cells of the mesenchyme-like areas and foci of epithelial-spindle cell transition were present. In some cases the mesenchyme-like component showed differentiated mesenchymal elements (usually skeletal muscle). Similar features were identified in 13 chemotherapy-treated cases of YST that consisted only of this mesenchyme-like component. The mesenchyme-like component of YST appears to represent a chemoresistant, pluripotential cell population arising from metaplasia of YST epithelium; it may give rise to sarcomas occurring in some patients with treated germ cell tumors.

Topics: alpha-Fetoproteins; Female; Humans; Immunohistochemistry; Keratins; Male; Mediastinal Neoplasms; Mesonephroma; Ovarian Neoplasms; Testicular Neoplasms; Vimentin

Ovarian endometrioid carcinomas resembling sex cord-stromal tumors (ECSCSs) may simulate Sertoli cell tumors, Sertoli-Leydig cell tumors (SLCTs), and adult granulosa cell tumors (AGCTs), both clinically and pathologically. Differing clinical features and histologic findings are almost always successful in distinguishing these tumor types, although in some cases the differential diagnosis is difficult. Immunohistochemical staining of 17 ECSCSs, 14 Sertoli cell tumors or SLCTs, and 15 AGCTs was performed with the use of antibodies against cytokeratins (AE1/AE3, 902, and CAM 5.2), epithelial tumor-associated antigens (EMA, OM-1, B72.3, and carcinoembryonic antigen B1.1), vimentin, S-100, neuron-specific enolase, and lysozyme to determine the immunohistochemical profile of each tumor type and to define further the nature of the sex cord-like components in ECSCSs. All 17 ECSCSs, none of the 15 AGCTs, and one of 14 Sertoli cell tumors or SLCTs stained with EMA. Staining for OM-1 was almost as helpful diagnostically, with positive results for 15 of 17 ECSCSs, 0/15 AGCTs, and 1/14 Sertoli cell or SLCTs. Antikeratins were immunoreactive with all the ECSCSs as well as some of the AGCTs and Sertoli cell tumors or SLCTs. The B72.3 and B1.1 were immunoreactive with some ECSCSs and Sertoli cell tumors, but were nonreactive with AGCTs. Neuron-specific enolase was demonstrated in 11 of 17 ECSCSs, two of 14 Sertoli cell tumors or SLCTs, and 0 of 15 AGCTs. Vimentin, S-100, and lysozyme were least helpful in the differential diagnosis. These studies suggest that an immunohistochemical approach may be useful in the differentiation of ECSCSs and sex cord-stromal tumors. Furthermore, it supports the conclusion that the sex cord-like cells in ECSCSs are not Sertoli or granulosa cells, but cells of surface epithelial type growing in architectural patterns similar to those of sex cord-stromal tumors.

Topics: Adenocarcinoma; Antigens, Tumor-Associated, Carbohydrate; Diagnosis, Differential; Endometriosis; Female; Granulosa Cell Tumor; Humans; Immunohistochemistry; Keratins; Leydig Cell Tumor; Lysosomes; Male; Ovarian Neoplasms; Phosphopyruvate Hydratase; S100 Proteins; Sertoli Cell Tumor; Testicular Neoplasms; Vimentin

Three cases of epididymal adenomatoid tumor are presented. The adenoid compositions of the tumors lined by epithelial cells showed a canalicular pattern with large vascular spaces, tubular pattern with glandlike regions or plexiform pattern with connective tissue strands. Immunohistochemistry demonstrated positive cytoplasmic staining for keratin, but negative for carcinoembryonic antigen and factor VIII-related antigen in each neoplastic tissue. These findings support the mesothelial origin of the epididymal adenomatoid tumors.

Topics: Adult; Carcinoembryonic Antigen; Epididymis; Humans; Keratins; Male; Mesothelioma; Middle Aged; Teratoma; Testicular Neoplasms; von Willebrand Factor

A fibrous pseudotumor of the testis from a 46-year-old man was examined histologically and immunohistochemically. The tumor, situated in the tunica vaginalis, appeared as multiple round nodules up to 2 cm in diameter, and was composed largely of fibrous tissue with scanty inflammatory cell infiltration. Besides mesothelial cells covering part of the tumor, foci of piled-up cells were found among the fibrous tumor tissue. The cells in the foci were spindle and polygonal in shape, and contained oval nuclei. Immunohistochemically, these cells were positive for vimentin and keratin, but negative for CEA. Similar features have been found in pleural mesothelioma, supporting the concept that testicular fibrous pseudotumor could represent neoplastic growth of the mesothelium of the tunica vaginalis.

Topics: Fibroma; Humans; Immunohistochemistry; Keratins; Male; Mesothelioma; Middle Aged; Testicular Neoplasms; Vimentin

The immunoprofiles of 121 germ cell and trophoblastic neoplasms were defined, using a battery of antibodies against cytokeratin (CK), vimentin (VIM), epithelial membrane antigen (EMA), placental alkaline phosphatase (PLAP), S-100 protein, leukocyte common antigen (LCA), UCHL-1, LN-2, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), chromogranin A, Leu-7, alpha-fetoprotein (AFP), alpha-1-antitrypsin (AAT), and the beta subunit of human chorionic gonadotropin (BHCG). In addition to 85 neoplasms of testicular origin, the cases included eight ovarian germ cell tumors and 28 extragonadal neoplasms. All tissues had been subjected to formalin fixation and paraffin embedding. Similar immunoreactivity patterns were seen in gonadal and extragonadal neoplasms, gestational and nongestational choriocarcinomas, components of mixed germ cell tumors and their pure counterparts, and metastatic and primary lesions. Placental alkaline phosphatase was a sensitive marker of germ cell differentiation, and expression of this marker in the absence of EMA appeared to be a staining pattern unique to germ cell tumors. Both LCA and S100 were absent in neoplastic germ cells, and thus were useful in differentiating these tumors from malignant lymphoma and malignant melanoma, respectively. Cytokeratin was helpful in distinguishing seminomas/dysgerminomas from nonseminomatous germ cell tumors, although 10% of seminomas showed focal or diffuse cytokeratin reactivity. Finally, 75% of all germ cell neoplasms displayed NSE, calling the specificity of this determinant into question.

Topics: Alkaline Phosphatase; alpha 1-Antitrypsin; alpha-Fetoproteins; Antibodies, Monoclonal; Antigens, Differentiation; Carcinoembryonic Antigen; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Female; Histocompatibility Antigens; Humans; Immunohistochemistry; Keratins; Leukocyte Common Antigens; Male; Membrane Glycoproteins; Mucin-1; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Peptide Fragments; Phenotype; Placenta; Pregnancy; Testicular Neoplasms; Trophoblastic Neoplasms; Vimentin

Features of hepatic and enteric tissue have been detected in serial sections of 2 out of 6 endodermal sinus tumors (EST) and embryonal carcinomas of the testis showing endodermal sinus areas. Hepatic nests, which appeared as tubules, cords and giant multinucleated cells, were PAS-positive as well as immunoreactive for alphafetoprotein (AFP) and cytokeratin (CK). Enteric tubules were found within EST areas and were characterized by their lack of cell atypism. The presence of diffuse PAS-, AFP- and CK-reactivity in cytoplasm, together with a brush border or an apical staining for CEA, were quite distinctive. EST showed a potential for both intra- and extraembryonal endodermic development and may be interpreted as a monophyletic teratoma.

Topics: alpha-Fetoproteins; Humans; Immunoenzyme Techniques; Immunohistochemistry; Intestine, Small; Keratins; Male; Mesonephroma; Spleen; Staining and Labeling; Testicular Neoplasms

Twenty-six intracranial germ cell tumours (11 germinomas, 10 teratomas, 2 endodermal sinus tumours, 1 teratocarcinoma, and 2 undifferentiated embryonal carcinomas) and 26 gonadal germ cell tumours (13 testicular seminomas, 2 ovarian dysgerminomas, 9 ovarian teratomas, and 2 myometrial choriocarcinomas) were studied by immunoperoxidase with monoclonal antibodies (MAbs) against epithelial membrane antigen (EMA), cytokeratin, and vimentin. Typical tumour cells in three of the 11 germinomas (two of the latter being situated in the posterior fossa) expressed both EMA and cytokeratin, whereas those in the seminomas and dysgerminomas did not. In one seminoma, a few multinucleated giant cells expressed cytokeratin. In three of seven germinomas, vimentin-positive tumour cells were found, but all seminomas and dysgerminomas were negative. In the other forms of intracranial and gonadal germ cell tumours, epithelial and mesenchymal elements displayed the expected patterns of immunoreactivity to the respective determinants. The immunoperoxidase differences between the intracranial germinomas and their gonadal equivalents indicate that, in the former, early epithelial or mesenchymal differentiation of the primordial germ cells may be present. The findings draw attention to the heterogeneous cellular composition of these otherwise morphologically homogeneous-appearing tumours and, especially in the posterior fossa, to their transitional links to the immature teratomas.

Topics: Adolescent; Adult; Antigens, Neoplasm; Brain Neoplasms; Child; Child, Preschool; Choriocarcinoma; Dysgerminoma; Epitopes; Female; Humans; Immunoenzyme Techniques; Infant; Keratins; Male; Membrane Glycoproteins; Mesonephroma; Middle Aged; Mucin-1; Ovarian Neoplasms; Teratoma; Testicular Neoplasms; Uterine Neoplasms; Vimentin

Seminomas are tumors of high proliferative activity and show a marked tendency towards local invasion with the capacity for interepithelial spread within the seminiferous tubules as well as into the rete ductules. Immunohistologic investigations were carried out on paraffin sections of 47 typical seminomas. Immunostaining with antibodies against cytokeratin and vimentin allows the convenient detection of even small rete residuals in cases of subtotal rete destruction as well as the identification of discrete interepithelial seminoma spread within the rete ductules, thus facilitating seminoma staging.

Topics: Dysgerminoma; Humans; Immunohistochemistry; Keratins; Male; Neoplasm Invasiveness; Neoplasm Staging; Testicular Neoplasms; Vimentin

A case of adenomatoid tumor arising from the epididymis is reported. A patient visited our hospital with complaint of a painless intrascrotal mass. Preoperative diagnosis was right epididymal tumor. Right epididymectomy was performed and histological diagnosis was adenomatoid tumor of the epididymis. We examined the histogenesis of this case by the immunoperoxidase technique. The tumor revealed cytoplasmic staining of tubular lining cells for keratin with no staining for myoglobin. This finding supported a mesothelial rather than endothelial derivation for this tumor. We found no muscle elements in this tumor.

Topics: Adult; Epididymis; Humans; Immunoenzyme Techniques; Keratins; Male; Teratoma; Testicular Neoplasms

Seminomas and non-seminomatous testicular germ cell tumours were studied for the presence of cytokeratin and vimentin filaments and desmosomes using immunohistochemical methods. In the majority of the classical seminomas and in seminomatous area of mixed tumours most tumour cells appeared to lack cytokeratin filaments. Some seminomas contained a focally variable proportion of cells exhibiting cytokeratin-positive structures while other cases contained only few seminoma cells with a well developed fibrillar cytokeratin network. Gel electrophoresis of cytoskeletal proteins from microdissected regions revealed cytokeratin polypeptides nos. 8 and 18 typical of simple epithelia. In one seminoma, however, all, or almost all, tumour cells contained cytokeratin filaments. This finding is in line with the assumption of transitional forms between seminoma and embryonal carcinoma. Despite the lack - or variable expression - of cytokeratin filaments most seminoma cells contained desmosomes, although often few in number and irregularly distributed at the circumference of the cells. Loosely arranged and often very sparse vimentin fibrils were found in many, but not all seminoma cells. Double label immunofluorescence microscopy suggested that the majority of desmosomes was associated with intermediate filaments of the vimentin type. In contrast, in carcinoma cells of malignant teratomas, in well differentiated epithelial cells of intermediate-type malignant teratomas and in trophoblastic cells present in trophoblastic-type malignant teratomas cytokeratin filament bundles as well as desmosomes were decorated. The arrangement and density of the cytokeratin filament skeleton and of desmosomes varied with degree of maturation of the tissue. The most regular distribution and intensive staining of cytokeratin filaments and desmoplakin was found in "mature" tissues. Vimentin was demonstrated in mesenchymal areas and stroma cells. The results show that seminomas are distinguished from most other germ cell and non-germ cell tumours by the presence of true desmosomes together with scanty vimentin filaments in most tumour cells. In addition, they indicate that seminoma cells can be heterogeneous in their cytoskeletal complement and may include cells with cytokeratin expression, indicative of a multipotential character of the initially transformed cell(s).

Topics: Adolescent; Adult; Antibodies; Antigen-Antibody Complex; Cytoskeletal Proteins; Cytoskeleton; Desmoplakins; Desmosomes; Dysgerminoma; Fluorescent Antibody Technique; Humans; Intermediate Filaments; Keratins; Male; Membrane Proteins; Microscopy, Electron; Testicular Neoplasms; Vimentin

A panel of monoclonal antibodies against different keratin polypeptides, epithelial glycoproteins, placental alkaline phosphatase and collagen type IV was used to evaluate immunohistochemically the expression of the target antigens in 30 different human testicular germ-cell tumours of various types. Antikeratin antibodies detecting markers of different routes of epithelial differentiation revealed remarkable similarity of differential expression of various keratins in epithelial structures of teratomas and combined tumours as compared with normal human epithelial tissues. A considerable proportion of embryonal carcinoma cells stained positively for keratins 8, 18 and 19, while a minor subpopulation of tumour cells in embryonal carcinomas, some seminomas and many atypical intratubular cells expressed keratins 8 and 18 but usually lacked keratin 19. Antibody RICEO-MFG-06.3, specific for epithelial glycoproteins, gave negative results with seminomas as opposed to positivity in all but two nonseminomatous tumours. All but two neoplasms showed positivity for placental alkaline phosphatase, thus supporting its reliability as a marker of germ-cell tumours. It is concluded that the monoclonal antibody RICEO-MFG-06.3 and especially the keratin-19-specific antibodies BA16 and BA17 can be helpful in distinguishing embryonal carcinoma from seminoma and, together with antibodies to other keratins, in the study of the origin and histogenesis of testicular germ-cell tumours.

Topics: Alkaline Phosphatase; Antibodies, Monoclonal; Cell Differentiation; Collagen; GPI-Linked Proteins; Humans; Immunoenzyme Techniques; Isoenzymes; Keratins; Male; Membrane Proteins; Mucin-1; Neoplasms, Germ Cell and Embryonal; Placenta; Teratoma; Testicular Neoplasms

Yolk sac tumor and seminoma may have a similar appearance in focal areas. Small biopsies may therefore be difficult to interpret. The authors studied 20 yolk sac tumors and 21 seminomas to investigate the utility of immunohistochemical markers in this differential diagnosis. All yolk sac tumors stained positively for cytokeratin (CK) but so did 43% of seminomas. The CK positivity of yolk sac tumors was generally more diffuse and intense, however, there was an overlap in the spectrum of intensity of CK positivity in yolk sac tumor and seminoma. Alpha-fetoprotein (AFP) was a less sensitive (55%) marker for yolk sac tumor than CK, but AFP was quite specific in this differential diagnosis because no seminoma stained for AFP. Alpha-1-antitrypsin was not a very useful marker because of poor sensitivity and specificity. The interpretation of light microscopic patterns remains of paramount importance in the differentiation of solid yolk sac tumor from seminoma.

Topics: alpha 1-Antitrypsin; alpha-Fetoproteins; Diagnosis, Differential; Dysgerminoma; Humans; Immunoenzyme Techniques; Keratins; Male; Mesonephroma; Neoplasm Proteins; Testicular Neoplasms

170 germ cell tumours of childhood and adolescence were studied by light microscopy and immunohistochemistry. The male-to-female ratio was 1:1.3. 52 (30.6%) tumours were benign (mature teratoma), 30 (17.6%) potentially malignant (immature teratoma), and 88 (51.8%) unequivocally malignant. The main locations were ovary, testis and sacrococcygeal region. 92 tumours were located in a gonad, 78 tumours in extragonadal sites (ratio: 1.2:1). Of the frankly malignant tumours 40 were yolk-sac tumours (YST) and an additional 19 tumours of more than one histological type contained a YST component. Therefore, 67% of the malignant tumours had a YST component. Children with immature teratoma and pure YST showed the lowest median age (5 and 24 months, respectively), while children with germinomas of various locations had the highest median age (153 months). A festoon pattern was the predominant histological feature in all YST and in the YST component of mixed germ cell tumours. Hyaline globules were found in 33/37 YST and in 16/17 YST components. Immunohistochemically, alpha 1-fetoprotein (AFP) was demonstrated in 18/22 YST and in 6/7 YST components of mixed germ cell tumours. Hyaline globules were mostly AFP-negative (only 5 cases with AFP-positive globules in addition to many AFP-negative globules). In 3 cases beta-HCG-positive giant cells were seen. In most YST prekeratin intermediate filaments could be demonstrated in the epithelial cells. Follow-up data, available from 51 cases of YST and tumours with YST components showed disease-free survival in 37 cases (72.5%). 10 patients (19.6%) died of disease, and 4 patients (7.8%) are living with disease. The comparably high rate of survivors reflects the effectiveness of modern therapy, particularly polychemotherapy, in addition to surgery.

Topics: Adolescent; alpha-Fetoproteins; Child; Child, Preschool; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Dysgerminoma; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Infant; Keratins; Male; Mesonephroma; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Peptide Fragments; Protein Precursors; Sacrococcygeal Region; Teratoma; Testicular Neoplasms

The immunohistochemical characteristics of 8 adenomatoid tumors of the epididymis are reported. Using the peroxidase antiperoxidase technique and the avidin-biotin complex method, antibodies against carcinoembryonic antigen, factor-VIII-related antigen and keratin were tested. In agreement with previous findings strong cytoplasmic staining for keratin was seen in all the tumors, whereas the factor-VIII-related antigen and carcinoembryonic antigen were absent. These results suggest a mesothelial origin of the adenomatoid tumor.

Topics: Carcinoembryonic Antigen; Epididymis; Epitopes; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Male; Teratoma; Testicular Neoplasms

A testicular tumor, removed from a 52-year-old man, was composed of uniform spindle cells and abundant interposed collagen, and was histologically diagnosed as a stromal tumor. Electron microscopy revealed cords of cells sometimes surrounded by a basal lamina. Desmosome-like junctions were found between some cells, and immunostaining for desmoplakins was positive. Immunofluorescence studies also showed cytokeratin-positivity in most and vimentin-positivity in some of the tumor cells. The presence of typical simple epithelial cytokeratins of Mr 40000, 45000 and 52000 was revealed by the western blotting method. Cytokeratin positivity in the tumor cells suggests the epithelial nature of this mesenchymal-looking tumor. The tumor might arise from cytokeratin-positive epithelial elements of the testis or its covering mesothelium, but the histogenesis remains unresolved. Our findings suggest that some of the so-called testicular stromal tumors may in fact be of epithelial nature by presenting features typical of epithelial differentiation.

Topics: Cell Differentiation; Cytoskeletal Proteins; Desmoplakins; Desmosomes; Electrophoresis, Polyacrylamide Gel; Epithelium; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Keratins; Male; Membrane Proteins; Microscopy, Electron; Middle Aged; Testicular Neoplasms; Vimentin

The monoclonal antibodies BA16 and BA17, reacting specifically with human keratin 19 (40 kD) have been tested by immunohistochemical staining methods for their reaction with a wide range of human tumours and cultured cells. Primary adenocarcinomas and their metastases showed a homogeneously positive reaction with greater than 95% of the tumour cells staining. Non-epithelial tumours, basaliomas and squamous cell carcinomas were unstained, while benign breast lesions and a thyroid adenoma show a mosaic pattern of stained and unstained (5-40%) cells. These three staining patterns were also seen in cultured cells. Positive homogeneous staining was seen in all breast cancer cell lines examined with the exception of PMC42, which exhibits stem cell characteristics, and which showed the heterogeneous pattern of staining seen in milk cell cultures. Non-epithelial lines and strains, two cell lines from cervical carcinomas and three SV40 transformed breast epithelial lines were unstained. The antibodies BA16 and 17 are potentially useful reagents for distinguishing adenocarcinomas (and their metastases) from non-epithelial tumours and from squamous carcinomas. They may also discriminate between benign and malignant breast lesions, and identify a specific differentiation phenotype in the secretory cell lineage.

Topics: Antibodies, Monoclonal; Breast Neoplasms; Cell Line; Cells, Cultured; Epitopes; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Keratins; Male; Neoplasms; Testicular Neoplasms

Topics: Adult; Aged; Antigens; Epididymis; Factor VIII; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Male; Mesothelioma; Middle Aged; Testicular Neoplasms; von Willebrand Factor

Four testicular adenomatoid tumors were studied by immunohistochemistry, using the following antibodies to cytokeratin, epithelial membrane antigen, carcinoembryonic antigen, and factor VIII-related antigen. Cytokeratin and epithelial membrane antigen demonstrated a different pattern of positive immunostaining while carcinoembryonic antigen and factor VIII-related antigen proved constantly negative. Our findings support a mesothelial origin for adenomatoid tumors.

Topics: Adult; Antigens; Antigens, Surface; Carcinoembryonic Antigen; Epithelium; Factor VIII; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Male; Teratoma; Testicular Neoplasms; von Willebrand Factor

Normal testicular tissue and 76 testicular germ-cell tumors of various types were immunohistochemically evaluated for the expression of intermediate filament proteins of different types. In normal testes, the rete testis epithelium was positive to cytokeratin, and the Sertoli cells, stromal cells, and Leydig cells were positive for vimentin. Cytokeratin-positive cells were also found lining atrophic seminiferous tubules and were occasionally seen within nonatrophic seminiferous tubules. The classical seminomas showed vimentin positivity, but this was usually observed in a small number of tumor cells. In addition, nearly half the seminomas contained single cytokeratin-positive cells, some of which were multinucleated and appeared to represent syncytiotrophoblastic giant cells. The tumor cells in embryonal carcinomas, endodermal sinus tumors, and choriocarcinomas displayed cytokeratin positivity. In some embryonal carcinomas vimentin-positive tumor cells were also found, probably representing attempts at further differentiation of the tumor cells. In immature teratomas, both the immature and the mature epithelial structures showed cytokeratin positivity. The stromal components, including cartilage, contained vimentin, and the smooth-muscle elements, desmin. Neural tissue positive for neurofilaments and glial tissue positive for glial fibrillary acidic protein, were observed in 5 and 3 of 15 cases, respectively. It is considered that antibodies to intermediate filaments are suitable tools to characterize the differentiation patterns of testicular germ-cell tumors and have the potential to aid in the differential diagnosis especially between seminoma and embryonal carcinoma.

Topics: Antibodies, Monoclonal; Choriocarcinoma; Desmin; Dysgerminoma; Fluorescent Antibody Technique; Histocytochemistry; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Male; Mesonephroma; Neoplasms, Germ Cell and Embryonal; Teratoma; Testicular Neoplasms; Testis; Vimentin

Topics: Adult; Humans; Keratins; Male; Rete Testis; Testicular Neoplasms

Thirteen primary and metastatic testicular germ cell tumours, including classical and anaplastic seminomas, and non-seminomatous testicular tumours were examined for their intermediate filament protein (IFP) types. The seminomas were shown to react with a monoclonal and a polyclonal antibody to bovine lens vimentin, while non-seminomatous germ cell tumours were strongly positive for a polyclonal and a monoclonal antibody to cytokeratin. In one case of seminoma with elevated serum levels of beta HCG and alpha FP, cytokeratin positive tumour cells were found. In the case of teratocarcinoma, several components of the tumour could be distinguished using a combination of antisera in double-label immunofluorescence microscopy. The glandular component of this tumour was positive with the polyclonal antikeratin, but also with the monoclonal cytokeratin antibody specific for glandular epithelia (RGE 53). However, the squamous component was negative with this latter antibody. Strikingly, the spindle cell component showed focal positivity for vimentin, with coexpression of cytokeratin and vimentin in some cells. Our data show that antibodies to cytokeratin and vimentin can be helpful in the diagnosis of testicular germ cell tumours, especially in the differentiation between seminomas and non-seminomatous tumours.

Topics: Antibodies, Monoclonal; Antibody Specificity; Cellulose; Dysgerminoma; Electrophoresis, Polyacrylamide Gel; Humans; Keratins; Male; Paper; Testicular Neoplasms; Testis; Vimentin

The mesothelial origin of epididymal adenomatoid tumor is supported by the current study for the presence of mesothelial antigen in the tumor cells. By an indirect immunoperoxidase technique, anti-mesothelial cell serum showed positive cytoplasmic staining in five of the six adenomatoid tumors studied. Previous findings of the presence of strong cytoplasmic keratin and the absence of carcinoembryonic antigen and Factor VIII-related antigen in these tumor cells are also confirmed by this study.

Topics: Antigens; Antigens, Neoplasm; Carcinoembryonic Antigen; Cytoplasm; Epididymis; Factor VIII; Humans; Immunoenzyme Techniques; Keratins; Male; Mesothelioma; Staining and Labeling; Testicular Neoplasms; von Willebrand Factor

Monoclonal antibodies to cytoskeletal proteins were used to study the intermediate filament proteins of human embryonal carcinoma (EC) cell lines, tumors produced in nude mice from these cell lines, and surgically removed testicular germ cell tumors. It was found that all cells of tumor lines 2102Ep, 1156 and Tera 1 react with antibodies to low molecular weight keratin proteins. By immunoblotting of SDS gels it was found that these lines expressed three keratin polypeptides (40K, 45K and 52K). Clonal line NTera-2 derived from Tera-2 differed from the above listed cell lines in that only 10% of the cells expressed the 40K keratin polypeptide. Upon treatment with retinoic acid 70% of NTera-2 cells became reactive with the antibody to the 40K keratin polypeptide. All cell lines contained a small population of vimentin-positive cells. The number of vimentin-positive cells could be increased by retinoic acid treatment of NTera-2 cells or by seeding the 2102Ep cells at low cell density. Neurofilament-positive cells could be induced in the cell line NTera-2 by retinoic acid treatment. Tumors produced from NTera-2 cells injected into nude mice contained cells reacting with antibodies to keratin, vimentin, neurofilament proteins and desmin. Keratin polypeptides were immunohistochemically demonstrated in embryonal carcinoma, yolk sac carcinoma and trophoblastic components of solid human germ cell tumors. Atypical intratubular cells ('carcinoma in situ') also reacted with antibodies to keratin.

Topics: Animals; Antibodies, Monoclonal; Cytoskeleton; Electrophoresis; Humans; Keratins; Male; Mice; Mice, Nude; Neoplasm Transplantation; Peptides; Teratoma; Testicular Neoplasms

The authors investigated the presence and distribution of keratin in germ cell tumors using a rabbit-anti-keratin antiserum and a monoclonal antikeratin antibody--which is specific for keratin classes of 40, 50, and 56.5 kdaltons--by various immunohistochemical methods on frozen sections, alcohol-fixed, and formalin-fixed paraffin-embedded tissues. Thirty-four germ cell tumors were studied. These were the following: 18 seminomas, 10 embryonal carcinomas, 2 teratocarcinomas, 3 yolk sac tumors and 1 choriocarcinoma. All seminomas, including four poorly differentiated (so-called anaplastic seminomas), gave negative results, regardless of the method employed. Embryonal carcinoma, the epithelial component of the teratocarcinoma, the yolk sac tumors, and choriocarcinoma were at least focally positive for keratin. The monoclonal antibody provided a cleaner background and stronger staining than the rabbit-anti-total-human-epidermal-keratin antibody. Best results were obtained from fresh-frozen sections or alcohol-fixed, paraffin-embedded materials. Formalin-fixed, nonseminomatous tumors, when predigested with trypsin and incubated overnight with primary antibody, gave no false-negative results but staining was often focal. The authors' results agree with the reported absence of detectable keratin in primordial germ cells of the normal testis, and with prevailing concepts of the histogenesis of germ cell tumors. These results indicate that the presence or absence of keratin by immunocytochemical methods can be helpful in distinguishing seminoma from embryonal carcinoma.

Topics: Antibodies, Monoclonal; Choriocarcinoma; Diagnosis, Differential; Dysgerminoma; Female; Frozen Sections; Humans; Immunologic Techniques; Keratins; Male; Mesonephroma; Ovarian Neoplasms; Pregnancy; Teratoma; Testicular Neoplasms; Uterine Neoplasms

A cloned human embryonal carcinoma (EC) cell line 2102Ep derived from a testicular teratocarcinoma was characterized by means of electron microscopy and immunohistochemistry. These EC cells when plated at high cell density grow mostly as undifferentiated cells displayed relatively little pleomorphism. Eighty-five to 90% of these cells contain keratin in the form of peridesmosomal tonofilaments. Cell populations of the same clonal line plated at a low cell density contain, in addition to undifferentiated EC cells, large cells displaying complex cytoplasmic architecture, more complex junctions, and intracytoplasmic keratin in the form of bundles. Some of these cells also react with antibodies to human chorionic gonadotropin indicative of trophoblastic differentiation. Furthermore, some cells form "morules" which are multicellular aggregates composed of a core of EC cells and an attenuated, more differentiated outer cell layer. These data thus point out not only some similarities but also even more prominent differences between human and mouse EC cells.

Topics: Animals; Antibodies; Cell Differentiation; Cell Line; Cell Nucleus; Chorionic Gonadotropin; Cytoplasm; Histocytochemistry; Humans; Intercellular Junctions; Keratins; Male; Mice; Teratoma; Testicular Neoplasms

Four adenomatoid tumors of the epididymis were evaluated immunohistologically for the expression of intermediate filaments and endothelial cell markers, factor VIII-related antigen and binding of Ulex europaeus I-lectin (UEA I). Immunofluorescence microscopy showed a strong reaction with antikeratin but not with anti-vimentin antibodies, indicating that adenomatoid tumor cells contain epithelial but not mesenchymal type of intermediate filaments. No staining of tumor cells was seen with anti-FVIII-related antigen antibodies or with fluorochrome-coupled UEA I. The results support the mesothelial, non-endothelial origin of adenomatoid tumors.

Topics: Adult; Aged; Antigens; Cytoskeleton; Epididymis; Factor VIII; Humans; Keratins; Lectins; Male; Middle Aged; Teratoma; Testicular Neoplasms; von Willebrand Factor