bromochloroacetic-acid and Carcinoma--Signet-Ring-Cell

We report a case of microcystic/reticular schwannoma of the proximal sigmoid colon in a 61-year-old man. A 12-mm polyp was detected while the patient was undergoing screening for colorectal neoplasm. This rare variant of schwannoma was initially described in 2008 and shows a predilection for the visceral organs, predominantly the gastrointestinal tract. We also review 11 other reported cases of microcystic/reticular schwannomas in the gastrointestinal tract. Unlike conventional gastrointestinal schwannomas, which are more common in the stomach, this variant appears to be more common in the large intestine. Histologic examination of this polyp showed predominant lipoblast-like vacuolated cells within a myxoid stroma with focal spindle cell areas. Features suggestive of malignancy, like nuclear pleomorphism, mitosis, or necrosis, were absent. Immunohistochemistry for S100 protein showed strong nuclear and cytoplasmic positivity, whereas cytokeratin and CD117 stains were negative. It is important to entertain microcystic/reticular schwannoma in the differential diagnosis of a signet ring cell adenocarcinoma or a myxoid gastrointestinal stromal tumor, particularly on small biopsy specimens.

Topics: Calgranulin A; Carcinoma, Signet Ring Cell; Colonic Neoplasms; Diagnosis, Differential; Gastrointestinal Stromal Tumors; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron, Transmission; Middle Aged; Neurilemmoma; Proto-Oncogene Proteins c-kit

Breast metastases from gastric cancer are extremely rare. A case report of a 37-year-old female with breast inflammatory invasion and ascites is described. Breast biopsy revealed carcinomatous invasion of the lymphatics from adenocarcinoma cells with signet-ring features. Estrogen (ER) and progesterone receptors (PR) and c-erb-B2 were negative. Upper gastrointestinal endoscopy revealed a prepyloric ulcerative mass. Histopathologic examination of the lesion showed infiltration from a high-grade adenocarcinoma, identical with that of the breast. Immunostaining was positive for cytokeratins CK-7 and CK-20 and CEA and negative for ER and PR. Ascitic fluid cytology was positive for adenocarcinoma cells. Mammography was not diagnostic. Abdominal CT scanning revealed large ovarian masses suggestive of metastases (Krukenberg's tumor). A cisplatin-based regimen was given but no objective response was observed. The patient died six months after initial diagnosis. A review of the literature is performed.

Topics: Adenocarcinoma; Adult; Ascites; Breast Neoplasms; Carcinoembryonic Antigen; Carcinoma, Signet Ring Cell; Female; Humans; Immunohistochemistry; Keratin-20; Keratin-7; Keratins; Ovarian Neoplasms; Stomach Neoplasms

Prostatic adenocarcinoma with a signet ring cell (SRC) component is a rare, incompletely characterized variant that must be distinguished from similar tumors of bladder or gastric origin. In this study, we used mucin and immunoperoxidase stains on formalin-fixed, paraffin-embedded sections from 12 prostatic adenocarcinomas with SRC components, with antibodies to prostate-specific antigen (PSA), cytokeratins, MIB-1, bcl-2, c-MET, CD44v6, and CD44v7; we performed a comparison study on six bladder and seven gastric carcinomas with SRCs. The prostatic SRC component was always associated with the usual high-grade adenocarcinoma. Both components were positive for PSA, AE1/AE3, and CAM 5.2 (12 cases of 12) and also expressed c-MET (5 cases of 9), CD44v6 (9 of 10), and CDv7 (9 of 10). Only rare cells stained for bcl-2 (3 cases of 9). The mean MIB-1 proliferation index was 8%. Intracellular mucin was identified (periodic acid-Schiff with diastase predigestion (PAS-D) in 9 cases of 10, mucicarmine in 5 of 10, alcian blue in 6 of 10). Bladder and gastric tumors were positive for PSA (3 cases of 6 and 2 of 7, respectively), using a polyclonal antibody, and for bcl-2 (5 cases of 6, 2 of 7), c-MET (6 of 6, 6 of 7), CD44v6 (5 of 6, 6 of 7), and CD44v7 (4 of 6, 4 of 7), with mean MIB-1 proliferation indices of 15 and 35%, respectively. All were negative for cytokeratin 34 beta E12. We conclude that prostatic adenocarcinomas with SRC components are typically accompanied by high-grade adenocarcinoma; are variably positive for mucin, with PAS-D being the most sensitive stain; show expression of PSA, cytokeratins, MIB-1, bcl-2, c-MET, and CD44 similar to that shown by high-grade adenocarcinoma components; have a low MIB-1 proliferation index; and are not always distinguishable from SRC components of bladder and stomach carcinomas with any of the above stains, including PSA.

Topics: Aged; Aged, 80 and over; Antigens, Nuclear; Biomarkers; Carcinoma, Signet Ring Cell; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Ki-67 Antigen; Male; Middle Aged; Nuclear Proteins; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies

A case of prostatic signet-ring adenocarcinoma is described in a man with a history of open prostatectomy for prostate carcinoma (18 years previously). Immunostaining confirmed the prostatic origin of the signet-ring tumor which stained for prostatic acid phosphatase (PSAP) and prostate specific antigen (PSA). Cytokeratin immunostaining showed the vacuoles to be true lamina with clear and distinct outlines, the feature confirmed by ultrastructural examination. This aggressive tumor is an uncommon but distinct variant of primary prostatic carcinoma which should be distinguished from artefactual vacuolation of tumor, inflammatory and stromal cells, and metastatic disease.

Topics: Aged; Carcinoma, Signet Ring Cell; Diagnosis, Differential; Fatal Outcome; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Neoplasm Recurrence, Local; Prostate-Specific Antigen; Prostatic Neoplasms

Topics: Carcinoma, Signet Ring Cell; Diagnosis, Differential; Endoscopy, Gastrointestinal; Gastric Mucosa; Gastritis; Humans; Keratins; Plasma Cells

Topics: Anus Neoplasms; Carcinoma, Signet Ring Cell; Colonoscopy; Fatal Outcome; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucins; Neoplasm Proteins

Topics: Aged; Carcinoma, Signet Ring Cell; Duodenal Neoplasms; Fatal Outcome; Humans; Immunohistochemistry; Jejunal Neoplasms; Keratins; Male; Mucins; Neoplasm Proteins

Topics: Biopsy; Carcinoma, Signet Ring Cell; Cicatrix; Fatal Outcome; Humans; Keratins; Linitis Plastica; Male; Middle Aged; Pulmonary Embolism; Skin Neoplasms; Stomach Neoplasms

We describe 3 cases of nonneoplastic signet-ring cell change in ulcerated mucosa, 2 of them in the gallbladder and 1 in an endocervical polyp. In the gallbladder cases, there were focal collections of signet-ring cells both on the mucosal surface and within the lumen of tubules, whereas in the endocervical polyp, the signet-ring cell aggregates were entirely confined to the mucosal surface. In all 3 cases, the signet-ring cells were positive for Mayer's mucicarmine and immunoreactive for keratin AE1/AE3. The lack of nuclear atypicality, the arrangement in superficial and intraluminal nests, and the admixture with histiocytes and other inflammatory cells are in keeping with the interpretation that the signet-ring cells are disrupted mucosal goblet cells exhibiting hyperplastic and degenerative changes. A review of the literature disclosed only other 2 previously reported cases of benign signet-ring cell changes in the gallbladder and none--to the best of our knowledge--in an endocervical polyp. Awareness of this phenomenon is of importance to avoid a potential overdiagnosis of signet-ring cell adenocarcinoma.

Topics: Adult; Carcinoma, Signet Ring Cell; Cervix Uteri; Diagnosis, Differential; Diagnostic Errors; Female; Gallbladder Diseases; Humans; Hyperplasia; Keratins; Male; Middle Aged; Mucous Membrane; Polyps; Ulcer; Uterine Cervical Diseases; Young Adult

We report the clinical and histopathological characteristics of two cases of signet ring cell carcinoma of the eye lids, and discuss the histogenesis of this neoplasm. Two 72-year-old Caucasian males both presented with slowly growing tumours of the eyelids. The tumours were excised and specimens were examined using light- and transmission electron microscopic techniques. Clinically, the tumours infiltrated both eyelids on one side of the face with swelling and periocular inflammation, creating a monocle-like appearance. Extensive clinical work-up excluded periocular metastases. Histopathologically, the tumours were composed of rather bland cells with mainly histiocytoid morphology. A minor proportion had a signet ring cell appearance. The cytoplasmic inclusions giving the signet ring morphology were PAS- and colloidal iron positive. The tumour cells reacted with antibodies against cytokeratins, carcinoembryonic antigen, epithelial membrane antigen, gross cystic disease fluid protein-15 and lysozyme. Transmission electron microscopy demonstrated tumour cells containing intracytoplasmic vacuoles lined by microvilli. The tumour cells aggregated in duct-like clusters. A diagnosis of primary signet ring cell carcinoma was made in both cases. Histopathological, immunohistological and ultrastructural findings indicated that the tumours were of sweat gland origin.

Topics: Aged; Aminosalicylic Acid; Carcinoembryonic Antigen; Carcinoma, Signet Ring Cell; Carrier Proteins; Eyelid Neoplasms; Glycoproteins; Histocytochemistry; Humans; Immunohistochemistry; Intranuclear Inclusion Bodies; Iron Compounds; Keratins; Male; Membrane Transport Proteins; Microvilli; Mucin-1; Muramidase; Sweat Gland Neoplasms

Synchronous tumors of the stomach are uncommon. We present a unique case of gastric synchronous tumors composed of signet-ring cell adenocarcinoma and gastrointestinal stromal tumor (GIST). The two tumors arose at the same site and were sharply juxtaposed without intermingling of morphologically distinct elements. Coincidence probably accounts for this occurrence, even if a common carcinogenic agent had been hypothesized. Preoperative imaging and endoscopic biopsy could lead to the suspicion of synchronous tumors, and an accurate histological identification of both tumors could be achieved by multiple deep endoscopic biopsies. The presence in our case of diffuse carcinomatosis indicates that the signet-ring cell adenocarcinoma had a greater adverse effect on the prognosis than the GIST.

Topics: Aged, 80 and over; Biomarkers, Tumor; Biopsy; Carcinoma, Signet Ring Cell; Endoscopy, Gastrointestinal; Gastrointestinal Stromal Tumors; Humans; Keratins; Male; Mucins; Neoplasms, Multiple Primary; Periodic Acid-Schiff Reaction; Stomach Neoplasms; Tomography, X-Ray Computed

Primary cutaneous signet ring cell carcinoma (PCSRCC) is a very unusual but distinctive clinicopathologic entity that can simulate metastatic adenocarcinomas. It is defined as a diffuse malignant epithelial neoplasia localized in the dermis and subcutis without epidermal involvement, showing variable amounts of signet ring cells, without evidence of visceral adenocarcinoma. We present 2 cases of PCSRCC, which involved eyelids and axilla respectively. Despite thorough systemic workup, primary sources could not be demonstrated in either case. The tumor cells are positive for gross cystic disease fluid protein 15 in addition to a variety of glandular markers. Furthermore, both cases were immunostained with cytokeratin 20 (CK20). In conclusion, we report 2 cases of PCSRCC expressing CK20 immunoreactivity. CK20-positive primary cutaneous tumors should include PCSRCC in addition to Merkel cell carcinoma.

Topics: Aged; Carcinoma, Signet Ring Cell; Humans; Keratin-20; Keratins; Male; Middle Aged; Skin Neoplasms

A 93-year-old woman developed a mass on her right lower eyelid that was present for more than 6 months but underwent rapid expansion during several weeks prior to her ophthalmological evaluation. Examination revealed an approximately 1.8 cm in diameter, fleshy, fungating growth involving more than 60% of the right lower eyelid. Excisional biopsy disclosed a neoplasm arising from the epidermis composed of adjoining basal cell and signet-ring squamous cell carcinoma, without a transition zone. The cells comprising the basal and squamous cell carcinomas were distinct immunophenotypically, with only the basal cell carcinoma reacting with Ber-EP4 and CAM 5.2 antibodies. To our knowledge, this case represents the first example of a collision tumor composed of basal cell and signet-ring squamous cell carcinoma.

Topics: Aged, 80 and over; Biomarkers; Biomarkers, Tumor; Carcinoma, Basal Cell; Carcinoma, Signet Ring Cell; Carcinoma, Squamous Cell; Eyelid Neoplasms; Female; Humans; Keratins; Neoplasms, Multiple Primary; Treatment Outcome

Metastatic tumors to the ovary are infrequently of urinary tract origin. In approximate descending order of frequency, this subset of secondary ovarian neoplasms includes renal cell carcinoma, transitional cell carcinoma of the urinary bladder, and urachal adenocarcinomas. These tumors usually raise a differential in turn of primary ovarian clear cell, transitional cell, or mucinous carcinomas. Only rare metastatic signet-ring adenocarcinomas of the bladder have shown the features of a Krukenberg tumor. We report the case of a 74-year old woman with bilateral Krukenberg tumors metastatic from a primary renal pelvic transitional cell carcinoma with glandular and signet-ring cell differentiation. This unique case reinforces that tumors with signet-ring cell morphology have a propensity to metastasize to the ovary, and indicates that renal pelvic carcinoma rarely may be the source of Krukenberg tumors.

Topics: Aged; Carcinoma, Signet Ring Cell; Carcinoma, Transitional Cell; Cell Differentiation; Cell Transformation, Neoplastic; Female; Humans; Immunohistochemistry; Keratin-20; Keratin-7; Keratins; Krukenberg Tumor; Ovarian Neoplasms; Prevalence; Urologic Neoplasms

Topics: Adenocarcinoma; Biomarkers, Tumor; Biopsy; Carcinoma, Signet Ring Cell; Diagnosis, Differential; Diagnostic Errors; Endometrial Neoplasms; Endometrium; Female; Humans; Keratins

Some examples of lobular carcinoma in situ (LCIS) may be composed in part of signet ring cells. Such proliferations have been considered examples of pleomorphic LCIS based on pathological features of the more conventional component. However, the occurrence of LCIS composed entirely of signet ring cells is extraordinarily rare. This report describes an example of an in situ proliferation that was composed almost entirely (>95%) of signet ring cells, which was unassociated with an invasive carcinoma and which showed comedo-type necrosis. There was only focal lobulocentric distention by lesional cells, as is typical of classic LCIS. However, discrete, ductal-type cross-sectional profiles showed a purely intraepithelial proliferation of remarkably discohesive signet ring cells. The signet ring cells had intermediate-grade nuclear atypia, no significant mitotic activity and were positive for mucicarmine and PAS stains (the latter with and without diastase predigestion). The cells displayed marked immunoreactivity for high-molecular-weight keratin (stained by 34beta E12 antibody), MUC1, gross cystic disease fluid protein-15, cytokeratin 7 and were negative for cytokeratin 20, E-cadherin, progesterone receptor and HER2/neu. It is concluded that this is an example of a purely signet ring variant of pleomorphic LCIS.

Topics: Adult; Antigens, Neoplasm; Biomarkers, Tumor; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Lobular; Carcinoma, Signet Ring Cell; Carmine; Cell Proliferation; Female; Humans; Immunohistochemistry; Keratins; Mucin-1; Mucins; Periodic Acid-Schiff Reaction; Treatment Outcome

Adenomatoid tumors are relatively uncommon benign neoplasms of mesothelial origin, usually occurring in the male and female genital tracts. Rare extragenital adenomatoid tumors have been identified in the adrenal glands, heart, mesentery, pleura, and lymph nodes. In the adrenal gland, adenomatoid tumors may pose a diagnostic challenge. The differential diagnosis includes adrenocortical carcinoma and metastatic carcinoma, especially signet ring cell carcinoma. Because of its glandular pattern, an adenomatoid tumor may be confused with an adenocarcinoma. We present 3 cases of adrenal adenomatoid tumors, including one with a concurrent large hemorrhagic vascular adrenal cyst. The adenomatoid tumors were unilateral, appeared solid and white, and varied from 1.7 to 4.2 cm in diameter. They occurred in 3 male patients aged 33, 33, and 46 years. One patient presented with abdominal pain due to the presence of a concurrent large adrenal cyst. The tumor was an incidental radiological finding in another case and was discovered during the course of a workup for hypertension in the third case. The light microscopic appearances were consistent with those of typical adenomatoid tumors. Immunohistochemical stains for calretinin and cytokeratin 5/6 were positive, confirming the tumors' mesothelial origin. Ultrastructural studies performed in 2 cases revealed microvilli and desmosomes. Follow-up showed no evidence of recurrence or metastasis. In our experience, the key to the diagnosis of this rare benign tumor is to consider adenomatoid tumor in the differential diagnosis of any glandular tumor occurring in the adrenal gland.

Topics: Adenocarcinoma; Adenoma; Adrenal Gland Neoplasms; Adult; Biomarkers, Tumor; Calbindin 2; Carcinoma, Signet Ring Cell; Cysts; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; S100 Calcium Binding Protein G; Treatment Outcome

We present a unique case of urothelial carcinoma of the right renal pelvis. It occurred in a 58-year-old woman. The tumor was located in the renal pelvis with extension into the adjacent renal medulla and cortex. Two years after surgical excision the patient is free of recurrence and metastasis. The tumor was well demarcated, without capsule, firm, solid, and whitish on the cut surface. It was 3x4 cm in largest diameter and without signs of necroses and hemorrhages. The tumor did not infiltrate the ureter. Histologically the predominant pattern of the tumor was adenocarcinomatous differentiation, and only very rare foci of urothelial carcinoma composed of typical transitional cells were found. No signs of intestinal type of metaplasia and adenocarcinoma, changes similar to the cystitis cystica or cystitis glandularis, were found in the tumor or in its vicinity. Most of the tumor looked like solid nests composed of cells with intracytoplasmic lumens. The resulting appearance was that of typical signet-ring cell change. These solid nests were usually surrounded by columnar epithelium, which in many areas formed papillary structures. A very striking feature was formation of collagen spherules. Small collagen spherules were often surrounded by a layer of the neoplastic cells so that collagenous rosettes were formed. In some areas these collagenous spherules clustered together so that they formed areas of collagenous spherulosis. The collagen in the spherules reacted positively with collagen IV. Ultrastructurally these spherules were formed by basal membrane-like material. Intracytoplasmic lumens of the signet-ring cell change were endowed by slender microvilli at ultrastructural level.

Topics: Carcinoma, Signet Ring Cell; Collagen; Female; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Kidney Pelvis; Microvilli; Middle Aged; Urothelium

A broad histomorphologic spectrum of ampullary carcinomas of Vater make a reproducible histologic classification difficult. Using cytokeratin immunohistochemistry, we present a new classification of ampullary carcinomas and analyze their clinical significance. Fifty-five invasive carcinomas of Vater's ampulla were histologically classified into pancreaticobiliary, intestinal, and other types. Serial sections of all carcinoma specimens were additionally stained with antibodies to cytokeratins (CK7, CK20), apomucins (MUC1, MUC2, MUC5AC), CEA, CA19-9, Ki67, and p53. Follow-up of patients from 4 months to 22 years after surgery (mean interval, 51.6 months) was evaluated. Most carcinomas of the ampulla of Vater were of immunohistochemically pancreaticobiliary type (iPT, CK7+, CK20-; 54.5%) or intestinal type (immunohistochemically intestinal type [iIT], CK7-, CK20+; 23.6%). Some carcinomas of immunohistochemically "other" type (iOT both CK7+ and CK20+ or CK7- and CK20-; 21.8%) had precursor lesions of iIT or iPT. Carcinomas positive for MUC2 or CEA were associated with iIT (MUC2, P < 0.001; CEA, P = 0.003), whereas MUC5AC-positive carcinomas were related to iPT (P = 0.005). Our classification based on cytokeratin-immunohistochemistry correlated well with the histologic classification according to published criteria (kappa-coefficient = 0.398; P < 0.001). Furthermore, histologically unusual types could be histogenetically related to pancreaticobiliary duct mucosa or intestinal mucosa. Therefore, all 4 signet-ring cell carcinomas were iIT carcinomas. Thus, cytokeratin immunohistochemistry allows a reproducible, histogenetically based categorization of ampullary carcinomas. However, neither histopathologic nor immunohistochemical subgroups significantly correlated with clinical outcome in our German collective. The overall survival was significantly shorter in males (P = 0.032) and patients with positive nodal stage (N1 < N0; P = 0.0025).

Topics: Aged; Ampulla of Vater; CA-19-9 Antigen; Carcinoembryonic Antigen; Carcinoma; Carcinoma, Signet Ring Cell; Common Bile Duct Neoplasms; Female; Follow-Up Studies; Gastric Mucins; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Ki-67 Antigen; Male; Middle Aged; Mucin 5AC; Mucin-1; Mucin-2; Mucins; Neoplasm Staging; Tumor Suppressor Protein p53

Signet ring cell carcinoma and glassy cell carcinoma are both rare histological subtypes of uterine cervical cancer. This report is of a case of uterine cervical carcinoma arising in a 29-year-old woman who had major components of signet ring cell carcinoma and glassy cell carcinoma within the same tumor. Histochemical and immunohistochemical analyses, including high and low molecular weight cytokeratins, p63 and MUC5AC, additionally demonstrated the squamous and adenocarcinomatous differentiation in the neoplastic cells, which showed otherwise unclassifiable morphology on the haematoxylin-eosin sections. A wide range of differentiation described above supports the speculation that glassy cell carcinoma may arise from the multipotential immature cells that can differentiate into both squamous and glandular cells. It would be precise to classify this tumor as adenosquamous carcinoma. Although adenosquamous carcinoma is not a rare histological subtype in the uterine cervix, it should be necessary to report the presence of glassy cells and signet ring cells when present because the presence of both components is associated with an unfavorable clinical behavior.

Topics: Adult; Biomarkers, Tumor; Carcinoma, Adenosquamous; Carcinoma, Signet Ring Cell; Chemotherapy, Adjuvant; DNA-Binding Proteins; Female; Genes, Tumor Suppressor; Humans; Immunohistochemistry; Keratins; Mucin 5AC; Mucins; Neoplasms, Multiple Primary; Phosphoproteins; Trans-Activators; Transcription Factors; Treatment Outcome; Tumor Suppressor Proteins; Uterine Cervical Neoplasms

In patients undergoing surgery for gastric cancer, as the resection area is difficult to define preoperatively, we define the resection area by intraoperative rapid pathological assessment of the resected margin. In some patients, however, the result of postoperative assessment of a permanent section differs from the result obtained intraoperatively. In this study we explored methods of improving the accuracy of intraoperative pathological assessment. Of the patients who underwent surgery for gastric cancer at Takarazuka Municipal Hospital, between April 2000 and July 2001, intraoperative pathological assessment of the resection margin was performed in 34 because it could not be accurately defined preoperatively. The intraoperative assessment consisted of touch smear cytological examination and hematoxylin and eosin (HE) and cytokeratin (CK) histological examination. The time required to perform cytological examination and HE and CK immunohistochemistry by this modified method, which uses an ENVISION Kit/HRP, was approximately 20 minutes for each procedure. Touch smear cytological examination gave false positive results in 3 of 34 patients (8.8%). Of the 14 patients preoperatively diagnosed with signet-ring cell carcinoma, intraoperative HE histological analysis yielded a false negative result in one (7.1%). The results of CK histological assessment of these patients were all consistent with those of postoperative examination of permanent sections. Of the 20 patients preoperatively diagnosed with non-signet-ring cell carcinoma, HE analysis yielded a false negative result in one (5%). The results of CK histological assessment of these patients were all consistent with those of postoperative examination of permanent sections. Our modified CK staining method with the ENVISION Kit/HRP allows intraoperative pathological assessment to be performed accurately and rapidly. This method is more useful than HE immunohistochemistry for the assessment of resected gastric margins.

Topics: Carcinoma, Signet Ring Cell; Humans; Immunohistochemistry; Intraoperative Period; Keratins; Reagent Kits, Diagnostic; Stomach Neoplasms

The sentinel node (SN) is the first lymph node in the lymphatic basin to be affected by metastasis from the primary tumour and is used to predict the status of the remaining nodes in the basin. We succeeded in detecting SNs of clinically early gastric cancers by intraoperative injection of a blue dye around the tumour. In the study presented here, multiple-marker reverse transcription-polymerase chain reaction (RT-PCR) was used to detect micrometastases in SNs and results were compared with those obtained with conventional histology. Expressions of cytokeratin-18 (CK-18), carcinoembryonic antigen (CEA), human telomerase reverse transcriptase (hTRT) and MUC-1 in SNs were determined by RT-PCR and Southern blot assay. Of the 213 SNs obtained from 35 cases of gastric cancer, eight nodes (3.8%) from five patients contained metastases that could be identified by conventional histology. However, CK-18 mRNA was expressed in 15 (7.0%), CEA in 12 (5.6%), hTRT in 10 (4.7%), and MUC-1 in 12 (5.6%) nodes, with at least one mRNA marker expressed in 25 nodes (11.7%) obtained from six patients. In the five patients with nodal metastases identified by conventional histology, two had metastases in both SNs and non-SNs. And, in the 30 patients without nodal metastases identified by conventional histology, one patient with micrometastases in the SNs identified by RT - PCR and Southern blot assay also had metastases in non-SNs as identified by serial sectioning and immunostaining of CK-18. All additional metastases were detected in non-SNs located in the same lymphatic basin as the previously detected SNs. This suggests that lymph node dissection of early-stage gastric cancer in the lymphatic basin may be mandatory even for patients without histologically detectable metastases in SNs.

Topics: Adenocarcinoma; Adenocarcinoma, Papillary; Blotting, Southern; Carcinoembryonic Antigen; Carcinoma, Signet Ring Cell; Case-Control Studies; DNA Primers; DNA-Binding Proteins; Gastrectomy; Humans; Keratins; Lymph Node Excision; Lymphatic Metastasis; Mucin-1; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Sensitivity and Specificity; Sentinel Lymph Node Biopsy; Stomach Neoplasms; Telomerase

We report a case of a 45-year-old woman who exhibited a primitive eccrine sweat gland carcinoma of the eyelid. Histological study showed cellular proliferation with an Indian file pattern and some signet ring cells with sialomucin secretion. Immunohistochemical study demonstrated these cells to be positive with the anticytokeratin, anti-EMA, anti-HMFG, antiestrogen receptor and antiprogesterone receptor antibodies. Ultrastructural study showed intracytoplasmic vacuoles with numerous microvilli at the apical side. Differential diagnosis with a metastasis from a mammary adenocarcinoma is difficult and a complete staging is necessary to confirm the primitive origin of the tumor. The behavior of this tumor is marked by locoregional recurrence.

Topics: Carcinoma, Signet Ring Cell; Eccrine Glands; Eyelid Neoplasms; Female; Humans; Keratins; Microvilli; Middle Aged; Receptors, Estrogen

We report a case in a 74-year-old woman of collecting-duct carcinoma of the kidney with prominent signet ring cell features. Grossly, the tumor measured 5.5 cm in greatest dimension, occupied the entire upper pole of the kidney, and was well circumscribed. Microscopically, it displayed a predominant tubulopapillary pattern of growth with a hyalinizing stroma. The tumor tubules were lined by a single layer of cells with large, pleomorphic nuclei, some of which had a hobnail appearance. Large intracytoplasmic vacuoles with compression of nuclei (signet ring cells) were present throughout the tumor. Alcian blue, mucicarmine, and periodic acid-Schiff stains failed to identify intracellular mucin or glycogen in the signet ring cells. Enlarged cells with intracytoplasmic vacuoles were also noted in the adjacent collecting ducts. The tumor cells were immunohistochemically positive for cytokeratin including cytokeratin 7, CAM 5.2, AE1/3, and 34 beta E12, vimentin, peanut lectin agglutinin, and Ulex europaeus agglutinin. Electron microscopy revealed that the intracytoplasmic vacuoles were due to intracellular edema. To the best of our knowledge, this is the first reported case of renal collecting-duct carcinoma with prominent signet ring cell features.

Topics: Aged; Biomarkers; Carcinoma, Signet Ring Cell; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Kidney Neoplasms; Kidney Tubules, Collecting; Lectins; Microscopy, Electron; Plant Lectins; Vimentin

Primary ovarian carcinomas with unusual histologic patterns can be difficult to differentiate from metastases. In this study, we reviewed 15 cases of mixed-epithelial carcinoma (12 serous, 1 serous and endometrioid, 1 endometrioid, 1 undifferentiated) with a predominant microcystic pattern and signet-ring cells. The patients' ages ranged from 31 to 78 (mean 58) years. The microcystic component in 11 patients had features of high-grade carcinoma and in 4 patients had features of low-grade carcinoma associated with areas of borderline tumor. The tumors in all 15 patients showed a predominant microcystic growth pattern composed of small cysts that were variable in size and shape. Signet-ring cells were also present in all cases (diffusely in nine cases, focally in six cases) within the neoplastic epithelial proliferation. Mucin was present in the lumina of some of the microcysts and in the cytoplasm of most of the signet-ring cells. A microcystic pattern and mucin-containing signet-ring cells can be seen as small foci or as a predominant component in primary epithelial nonmucinous ovarian carcinomas. It is important for pathologists to recognize these unusual findings in ovarian neoplasms, because they may produce a confusing apperance, even potentially suggesting a metastasis.

Topics: Adult; Aged; Carcinoma; Carcinoma, Endometrioid; Carcinoma, Signet Ring Cell; Cell Nucleus; Cystadenocarcinoma; Cystadenocarcinoma, Papillary; Cytoplasm; Female; Humans; Keratins; Middle Aged; Mucins; Ovarian Cysts; Ovarian Neoplasms

We describe the clinicopathological characteristics of 15 cases of primary signet ring cell adenocarcinoma of the lung and highlight the importance of recognizing that not all adenocarcinomas with signet ring cell features represent metastatic adenocarcinomas.. We evaluated the clinicopathological and immunohistochemical features of 15 cases of signet ring cell adenocarcinoma of the lung. The patients were 12 men and three women, age 30-75 years (mean 52.5 years). No evidence of a primary tumour elsewhere could be found on thorough clinical examination. Nine patients underwent resection and the remainder were biopsied. The tumours ranged from 18 to 80 mm in greatest dimension. Microscopically, two distinct patterns of growth were recognized: acinar and diffuse. The tumours were characterized by the presence of >75% signet ring cells. Periodic acid-Schiff and mucicarmine showed strong intracellular positive staining. Immunohistochemical stains for TTF-1 (6/6) and CEA (9/9) showed strong positive reaction in all cases evaluated. Three out of six cases were also positive for cytokeratin 7. All the tumours (6/6) were negative for cytokeratin 20, ER, PR and GCDFP-15. Follow-up information was obtained in 11 patients; six patients died within 1 year and five patients were alive from 3 to 36 months after initial diagnosis.. These cases highlight an unusual histological growth pattern of primary lung adenocarcinoma that may be mistaken for a metastasis from an occult primary. The recognition of this pattern of lung tumours is important for proper treatment.

Topics: Adult; Aged; Carcinoembryonic Antigen; Carcinoma, Signet Ring Cell; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Lung Neoplasms; Male; Middle Aged; Nuclear Proteins; Thyroid Nuclear Factor 1; Transcription Factors

Signet-ring cell carcinoma (SRCC) of lung is a rare variant of pulmonary adenocarcinoma. In view of this rarity, the question of whether an SRCC is primary pulmonary or metastatic arises frequently because the majority of SRCCs seen in lung are metastatic tumors having arisen in stomach, colon, or breast. On routine histologic examination it is difficult to distinguish between pulmonary SRCC from SRCC metastasizing from other organs. Thyroid transcription factor-1 (TTF-1) is a homeodomain-containing transcription factor that is almost exclusively expressed in thyroid and pulmonary epithelial cells. TTF-1 expression has been demonstrated in various neoplasms of lung; however, the expression of TTF-1 in SRCCs has not been investigated so far. In the present study, using an immunoperoxidase staining procedure on paraffin sections, we investigated the expression of TTF-1, cytokeratin 7, cytokeratin 20, and villin (a specific marker expressed in tumors of the digestive tract, renal proximal tubules, and hepatic bile ducts) in 32 SRCCs from various organs (17 lung, 5 breast, 5 stomach, and 5 colon). Fourteen (82.4%) of 17 pulmonary SRCCs exhibited TTF-1 positivity, whereas none of the SRCCs of other organs were positive for TTF-1. A cytokeratin profile (CK7+/CK20-) was identified in 94.1% of pulmonary SRCC, and although it differed from the profile exhibited in colonic SRCCs (CK7-/CK20+), a similar profile was seen in breast SRCCs and some SRCCs arising in the stomach. Villin was identified in 29.4% of pulmonary SRCCs and 20% (one case) arising in the breast. Although the pattern of villin immunostaining exhibited by nondigestive tract SRCCs (cytoplasmic) differed from those of digestive tract SRCCs (membranous), distinguishing between the two groups based on their pattern of immunostaining alone would be difficult. The results of this study indicate that TTF-1 is expressed in a high percentage of pulmonary SRCCs and is very specific and that TTF-1 would be extremely valuable in distinguishing pulmonary SRCCs from those arising in other organs.

Topics: Biomarkers, Tumor; Carcinoma, Signet Ring Cell; Carrier Proteins; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lung Neoplasms; Microfilament Proteins; Neoplasm Metastasis; Nuclear Proteins; Sensitivity and Specificity; Thyroid Nuclear Factor 1; Transcription Factors

We describe a case of benign signet ring cell change in the gallbladder mucosa. On histopathological examination of H&E-stained sections, the gallbladder epithelium showed multilayering. The epithelial cells were large, columnar to polygonal with a small round basal or eccentric nucleus and vacuolated cytoplasm, giving them a signet ring appearance. There was no nuclear atypia, hyperchromatism or mitotic activity. The cells showed uniform positivity with mucicarmine, PAS and Alcian blue stains. The cytoplasmic vacuolations were negative for fat stains (Oil red O and Sudan IV). On immunohistochemistry, the cells showed positivity with antibodies for pancytokeratin (PCK) and epithelial membrane antigen (EMA). A diagnosis of benign signet ring cell change with multilayering in the gall bladder mucosa was made. Thoroughly reviewing the literature, we found only one case of benign signet ring cell aggregates in the gallbladder mucosa documented earlier. The lesion is hereby reported because of the unique histomorphology and the diagnostic dilemma which can occur as a malignant change in situ has to be excluded.

Topics: Adult; Carcinoma, Signet Ring Cell; Cholecystectomy; Diagnosis, Differential; Epithelium; Gallbladder Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Mucin-1; Mucous Membrane

To study the distinctive clinicopathologic and immunohistochemical difference between ovarian metastatic carcinomas and primary ovarian carcinomas.. The clinical and pathological features of 27 cases of ovarian metastatic carcinomas (gastric carcinomas 12 cases, colon carcinomas 11 cases, others 4 cases) obtained from our department were reviewed. Immunostainings for CK (AE1/AE3), CK7, CK20, CEA, vimentin, nm23 were performed with SP staining methods.. On gross examination, metastasis from gastric adenocarcinoma were usually bilateral, while solid (11/12) and metastases from colonic adenocarcinoma were more often unilateral and cystic (7/11). Microscopically, metastases from gastric adenocarcinoma revealed signet ring cells or poorly differentiated adenocarcinomas (12/12), whereas metastases from colonic adenocarcinomas showed similar morphology of endometrioid adenocarcinoma (8/11). The majority of ovarian metastases of gastric carcinoma (7/12) and colon carcinoma (8/11) were CK20 positive. In particular, CK20 was invariably expressed in colon cancer metastases. Most of the ovarian metastatic carcinomas from the gastrointestinal tract failed to react with immunostaining of CK7. A combined use of CEA, vimentin and nm23 had made a correct classification for 11/12 cases of the gastric carcinoma, 10/11 cases of the colonic cancer.. CK7 and CK20 have been proved to be useful antibodies in distinguishing between metastatic carcinomas and primary carcinomas of the ovary. Combined use of a panel of antibodies can give more significant results.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Breast Neoplasms; Carcinoembryonic Antigen; Carcinoma, Endometrioid; Carcinoma, Signet Ring Cell; Colonic Neoplasms; Diagnosis, Differential; Female; Follow-Up Studies; Genes, Tumor Suppressor; Humans; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Middle Aged; NM23 Nucleoside Diphosphate Kinases; Nucleoside-Diphosphate Kinase; Ovarian Neoplasms; Stomach Neoplasms; Vimentin

Colon signet ring cell adenocarcinomas are uncommon, high-grade neoplasms. Given their rarity, the question of primary colon or metastatic gastric adenocarcinoma frequently arises when signet ring cell carcinoma is seen in a colonoscopic biopsy or in biopsies procured from other regions of the body. A second related question regarding colon and gastric signet ring cell carcinomas is their immunophenotypic similarities with the glandular form of adenocarcinoma in each site. We studied the immunohistochemical phenotype of 14 colonic signet ring cell adenocarcinomas and compared them with immunophenotype of 27 gastric signet ring cell adenocarcinomas. We also compared the immunophenotype of the 27 gastric signet ring cell with the immunophenotype of 19 gastric gland-forming adenocarcinomas, and the immunophenotype of the 14 colonic signet ring cell adenocarcinomas to the immunophenotype of 20 colonic gland-forming adenocarcinomas to identify staining differences in the neoplastic cells of the two architectures. Antibodies studied were cytokeratins 7, 17, 19, and 20, CA 19-9, CA-125. estrogen receptor, and gross cystic disease fluid protein 15. Sixty-four percent of colon signet ring cell adenocarcinomas had either no staining or focal staining with cytokeratin 7 compared with diffuse staining in 63% of gastric signet ring cell adenocarcinomas (P = 0.016). Seventy-two percent of colon signet ring cell adenocarcinomas had diffuse staining with cytokeratin 20 compared with no or focal staining in 50% of gastric signet ring cell adenocarcinomas (P = 0.019). Fifty-seven percent of the colon signet ring cell adenocarcinomas had a cytokeratin 7 (-)/cytokeratin 20 (+) staining pattern compared with 11% of gastric signet ring cell adenocarcinomas (P = 0.004). Forty-four percent of gastric signet ring cell adenocarcinomas had a cytokeratin 7 (+)/cytokeratin 20 (-) pattern, compared with none of the colon signet ring cell adenocarcinomas (P = 0.004). The staining distribution of the antibody battery was similar in colon signet ring cell and colon glandular adenocarcinoma and gastric signet ring cell and gastric glandular adenocarcinomas. When signet ring cell adenocarcinoma is encountered in a colon biopsy, a colon primary is supported if the neoplastic cells have a cytokeratin 7 (-)/cytokeratin 20 (+) staining pattern, and a gastric primary is supported if they have a cytokeratin 7 (+)/cytokeratin 20 (-) staining pattern. The signet ring morphology at each site had an

Topics: Adenocarcinoma; Apolipoproteins; Apolipoproteins D; CA-125 Antigen; CA-19-9 Antigen; Carcinoma, Signet Ring Cell; Carrier Proteins; Colonic Neoplasms; Glycoproteins; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Membrane Transport Proteins; Receptors, Estrogen; Stomach Neoplasms

Metastatic signet ring cell carcinomas of unknown primary site can represent a clinical problem. Gastrointestinal signet ring cell carcinomas and invasive lobular carcinomas of the breast are the most common sources of these metastases. Immunohistochemical algorithms have been successfully used in the search for the unknown primary adenocarcinomas. In the present study a series of primary invasive lobular breast carcinomas (79 cases) and their metastases and a series of gastrointestinal signet ring cell carcinomas (22 primary and 13 metastases) were stained with monoclonal antibodies for cytokeratin (CK) 20 and CK7 and for estrogen receptors (ER). The staining was evaluated as negative (no staining), focally (less than 10% of the tumor cells stained) or diffusely positive. All the primary and metastatic gastrointestinal signet ring cell carcinomas proved to be CK20 positive, while only 2/79 (3%) of the primary and 1/21 metastatic lobular carcinomas (5%) stained positively for this CK. None of the gastrointestinal carcinomas and the majority of the lobular carcinomas expressed ER. The majority of the tumors were CK7+. Using CK20 alone, 33 of 34 metastases could be properly classified as gastrointestinal (CK20+) or mammary (CK20-). ER identified 31/34 of breast cancer metastases. By combining the results of CK20 and ER staining all the metastases could be properly classified as the CK20+/ER- pattern identified all the gastrointestinal tumors.

Topics: Antibodies, Monoclonal; Breast Neoplasms; Carcinoma, Signet Ring Cell; Colorectal Neoplasms; Diagnosis, Differential; Esophageal Neoplasms; Female; Gastrointestinal Neoplasms; Humans; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lymphatic Metastasis; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms, Unknown Primary; Receptors, Estrogen; Stomach Neoplasms

Topics: Adult; Antigens, CD; Carcinoma, Signet Ring Cell; Diagnosis, Differential; Female; Humans; Immunoglobulins; Keratins; Liposarcoma; Lymphoma, B-Cell; Mandibular Neoplasms; Melanoma; Organelles; S100 Proteins; Vimentin

Serum assays for CA 125 are often used in the diagnosis and follow-up of patients with gynecologic neoplasms. A case of a 34-year-old woman with desmoplastic small round cell tumor (DSRCT) having an unusual morphology, including the presence of a signet ring cell component, and high serum CA 125 levels that was initially diagnosed as poorly differentiated carcinoma of the ovary is herein reported. Ultrastructurally, the signet ring appearance was shown to be the result of either the presence of intracytoplasmic vacuoles or dilatation of the intercellular space. Immunoperoxidase staining showed strong reactivity for desmin, keratin, vimentin, and CA 125. Immunohistochemical studies were performed on six additional DSRCTs but only two showed focal staining for CA 125. Because the patient's CA 125 serum level decreased after she received chemotherapy and her tumor was removed, and it became elevated again when the disease recurred, it is possible that CA 125 could be used as a marker of persistent and recurrent disease in those uncommon cases of DSRCT in which there are elevated serum levels of this marker at the onset of treatment.

Topics: Adult; CA-125 Antigen; Carcinoma, Signet Ring Cell; Carcinoma, Small Cell; Desmin; Fatal Outcome; Female; Humans; Immunoenzyme Techniques; Keratins; Neoplasm Recurrence, Local; Ovarian Neoplasms; Vimentin

We describe three cases of benign signet-ring cell aggregates in the colon associated with pseudomembranous colitis, adenomatous polyp of the colon and ulcerated mucosa of the gallbladder excised for gallstones. In all cases, we found loose, benign signet-ring cell aggregates overlying the ulcerated mucosa surface, simulating signet ring-cell carcinoma. The most important sign of the benign signet-ring cell aggregates is that they are always confined to the surface of the mucosa of the intestine or gallbladder mucosa or crypts of the intestinal epithelium. In no case did we see an invasion of these cells into the lamina propria of the mucosa. In all cases, the benign signet-ring cell aggregates were immunohistochemically positive with antibodies to cytokeratins. The occurrence of benign signet-ring cell aggregates is a rare and very misleading diagnostic pitfall which must be differentiated from signet-ring cell carcinoma of the colon and gallbladder.

Topics: Adenomatous Polyps; Carcinoma, Signet Ring Cell; Colonic Neoplasms; Diagnosis, Differential; Enterocolitis, Pseudomembranous; Female; Gallbladder Neoplasms; Humans; Immunohistochemistry; Intestinal Mucosa; Keratins; Male; Middle Aged

A case of distinctive benign cystadenoma of the parotid gland composed of several different morphological components is presented. The most conspicuous morphological component and the largest part of the neoplasm was represented by solid sheets of oncocytic cells surrounded by myoepithelial cell layer. Most oncocytic cells possessed large intracytoplasmic vacuoles with the nuclei displaced towards the periphery, imparting them with a striking signet-ring cell appearance. The size of the intracytoplasmic vacuoles ranged from 4 to 50 microm. Immunohistochemically these signet-ring cells lacked immunoreactivity for S-100 protein and cytokeratin but they strongly stained for antimitochondrial antibody 113-1. The present case illustrates an unusual, hitherto undescribed, morphological feature of benign oncocytic cystadenoma of the parotid gland.

Topics: Actins; Adenoma, Oxyphilic; Aged; Carcinoma, Signet Ring Cell; Cystadenoma; Female; Humans; Immunoenzyme Techniques; Keratins; Mitochondria; Parotid Neoplasms; S100 Proteins; Vacuoles

We describe a 60-year-old woman with leg pain. Although metastatic bone tumor and atypical cells mimicking signet-ring cells in the bone marrow picture were observed, systemic survey revealed no primary lesion. The patient died two months after admission from systemic progress of the disease. Autopsy revealed a small focus of adenocarcinoma within the right upper lobe of the lung and systemic metastases without any particular changes in the gastrointestinal tract. The tumor cells of the lung were diffusely positive for cytokeratin 7, whereas cytokeratin 20 immunoreactivity was weak and focal, and that supported the lung origin of the present tumor. Moreover, the tumor cells in the bone marrow showed a similar pattern in immunoreactivity. These findings suggest that cytokeratin 7 and cytokeratin 20 immunoreactivity is helpful for the premortem diagnosis of the metastatic tumor of unknown origin.

Topics: Biomarkers, Tumor; Bone Marrow; Bone Neoplasms; Carcinoma, Signet Ring Cell; Digestive System; Female; Fibula; Humans; Keratins; Lung; Lung Neoplasms; Middle Aged; Neoplasm Proteins; Neoplasms, Unknown Primary; Organ Specificity; Protein Isoforms; Radionuclide Imaging

A rectal adenocarcinoma in a 22-year-old capped langur histologically resembling those in human cases is reported. An ill-defined diffuse tumor with fibrously firm rectal wall showed diffuse infiltrative growth of signet-ring cancer cells. Immunohistochemistry demonstrated positive staining for CEA, lysozyme, EMA, keratin and B72.3.

Topics: Animals; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Signet Ring Cell; Cercopithecidae; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Microvilli; Mucin-1; Mucins; Muramidase; Neoplasm Proteins; Primate Diseases; Rectal Neoplasms