bromochloroacetic-acid and Carcinoid-Tumor

Several case reports have emphasized that esophageal carcinoid tumors are associated with a poor prognosis. To expand our knowledge about the pathology and biologic behavior of these rare tumors, we reviewed the clinicopathologic and immunohistochemical findings of four cases of primary esophageal carcinoid. The age of the patients ranged from 48 to 82 years (mean 63 years; median 61 years). The lower segment of the esophagus was involved in two cases and the mid segment was involved in one case. The sizes of the tumors ranged from 0.3 cm to 3.5 cm. Two tumors were confined to the lamina propria and two invaded into the muscular wall. Two tumors appeared polypoid, whereas the remaining two were incidental findings and associated with adenocarcinoma arising in a background of Barrett esophagus. The adenocarcinoma was superficially invasive in one case, whereas it penetrated the muscular wall in the other. All four carcinoid tumors were immunoreactive with chromogranin and synaptophysin. There was focal expression of serotonin in two cases, glucagon in one case, and pancreatic polypeptide in one case. Endocrine cell hyperplasia was noted in both the Barrett esophagus and the invasive adenocarcinoma. One patient died secondary to postoperative pneumonia. Three patients are alive and disease free at 1, 6, and 23 years status post therapy. None of the patients had metastatic disease. These findings show that esophageal carcinoids are associated with a favorable prognosis. They arise in two settings: (1) a single large polypoid tumor or (2) an incidental finding and in association with adenocarcinoma arising in the background of Barrett esophagus. The presence of endocrine cell hyperplasia in the Barrett mucosa and the adenocarcinoma supports the hypothesis that these lesions arise from a common stem cell.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Barrett Esophagus; Carcinoid Tumor; Chromogranins; Esophageal Neoplasms; Female; Gastrins; Glucagon; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Pancreatic Polypeptide; Polyps; Prognosis; Synaptophysin

The problems with classification and diagnosis of bronchopulmonary carcinoid and other neuroendocrine tumors are described in this paper. Single neuroendocrine cells and so-called neuroepithelial bodies found in normal bronchial epithelium are currently believed to constitute pulmonary components of an extensive neuroendocrine system. In view these opinions, it has appeared a need for a new, standardized nomenclature. Hence presently suggested classification of neuroendocrine carcinomas taking into account their histological structure, immunohistochemical as well as prognostic features starting from carcinoid tumors to small cell anaplastic carcinomas-includes three types of neoplasms.

Topics: Biomarkers, Tumor; Bronchial Neoplasms; Carcinoid Tumor; Carcinoma, Neuroendocrine; CD57 Antigens; Cell Size; Chromogranin A; Chromogranins; Humans; Keratins; Lung Neoplasms; Neoplasm Proteins; Neuroendocrine Tumors; Neuropeptides; Phosphopyruvate Hydratase; Silver Staining; Somatostatin; Synaptophysin; Terminology as Topic

The aim of this article is to present a case of primary neuroendocrine tumor (typical carcinoid) of the mandible that occurred in a 46-year-old black woman who was seropositive for the human immunodeficiency virus. Radiologically the lesion presented as a poorly circumscribed honeycomb radiolucency that extended from tooth 21 to the ascending ramus. Histologically the tumor cells were variously arranged in small islands, trabeculae, follicles, and slitlike spaces lined by a single layer of palisaded low-columnar cells. The follicles contained an eosinophilic colloid-like substance. Immunocytochemical staining showed diffuse, intense positivity for MAK 6, pancytokeratin, S-100, and neuron-specific enolase and focal, intense, positive staining for chromogranin A. Electron microscopy showed the presence of interdigitating cell membranes, rudimentary cell attachments, and varying numbers of membrane-bound dense core granules. Special investigations failed to reveal a primary tumor, and no metastases were found. Urine and hematologic assessment did not show any evidence of functional activity. The tumor was resected, and no recurrence or spread has been seen for 2 years. Origin from foregut-derived, immature, and functionally uncommitted endocrine cells is presumed.

Topics: Carcinoid Tumor; Cell Lineage; Cell Membrane; Chromogranin A; Chromogranins; Colloids; Cytoplasmic Granules; Eosinophils; Female; HIV Seropositivity; Humans; Immunohistochemistry; Intracellular Membranes; Keratins; Mandibular Neoplasms; Microscopy, Electron; Middle Aged; Phosphopyruvate Hydratase; Radiography; S100 Proteins

We evaluated three cases of pigmented pulmonary carcinoid tumors that were retrieved from the files of the Armed Forces Institute of Pathology, Washington, DC. Clinical follow-up showed no indication of tumor recurrence or metastases, nor was there evidence of malignant melanoma. All three cases exhibited histologic features of typical carcinoid tumor; there were focal oncocytic changes in two cases. Finely dispersed, brown pigment, believed to be melanin, was distributed in two different patterns: in sustentacular cells (case 1) or within the tumor cells (cases 2 and 3). Fontana-Masson stain was positive in areas of this pigment in all cases. The tumor cells showed immunoreactivity for chromogranin, synaptophysin, keratin (AE1/AE3 and CAM-5.2), and S100 protein in all cases. Focal staining for vimentin and corticotropin was seen within neoplastic cells in two cases. The pigmented sustentacular cells in case 1 showed focal immunoreactivity for S100 protein and HMB-45. Ultrastructural studies of paraffin-embedded tissues were performed in two cases. They showed well-developed melanosomes in the pigmented sustentacular cells in case 1. In both cases, cytoplasmic neurosecretory-type granules were identified in neoplastic cells. These findings demonstrate that pigmented pulmonary carcinoid tumor has an immunohistochemical profile similar to that of typical pulmonary carcinoid tumor. In some instances, pigmented pulmonary carcinoid tumors may show ultrastructural evidence of melanocytic and neuroendocrine differentiation. These immunohistologic and ultrastructural findings distinguish pigmented pulmonary carcinoid tumor from malignant melanoma and support the concept of "multidirectional cellular differentiation."

Topics: Adult; Aged; Antibodies, Monoclonal; Carcinoid Tumor; Chromogranins; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Middle Aged; Pigmentation; S100 Proteins; Synaptophysin

In a 52-year-old Caucasian man osteopoikilosis had been misdiagnosed roentgenologically 2 years before his death. Gradually he developed Cushing's syndrome and ultimately superior vena caval obstruction. At autopsy a primary thymic carcinoid with extensive osteoblastic bone metastasis was found. Immunohistochemically the tumor was shown to be positive for adrenocorticotropic hormone (ACTH), cytokeratin (KL1), neuron-specific enolase, synaptophysin, chromogranin and glucagon. Remarkably the tumour was negative for serotonin despite high urinary hydroxyindolacetic acid levels. Bilateral hyperplasia of the adrenal cortex was found. The adenohypophysis showed a considerable reduction of ACTH-producing cells and numerous Crooke's cells with a characteristic immunohistochemical pattern.

Topics: Adrenal Cortex; Adrenocorticotropic Hormone; Bone Neoplasms; Carcinoid Tumor; Cushing Syndrome; Diagnostic Errors; Humans; Keratins; Male; Middle Aged; Osteopoikilosis; Phosphopyruvate Hydratase; Radiography; Thymus Neoplasms; Vena Cava, Superior

Carcinoid neoplasms, although rare, have to be considered in the differential diagnosis of neoplasms of the larynx. The total number of cases reviewed and listed in the present article is 47. The gross appearance of carcinoid tumours is not characteristic and does not differ from that of other malignant neoplasms of the larynx. Under the light microscope various types can be distinguished, which are described and illustrated in this review article. Available material of five previously published cases and of one new case have been re-examined under the electron microscope and by modern histochemical and immunohistochemical methods. The ultrastructural presence of neurosecretory granules and of argyrophilia by the Grimelius technique were uniformly positive, together with monoclonal antibodies for somatostatin and keratin. These special methods offer a reliable basis for the diagnosis of neuroendocrine neoplasms to which carcinoid tumours belong. The treatment of carcinoid neoplasms of the larynx is surgical.

Topics: Adult; Aged; Aged, 80 and over; Carcinoid Tumor; Carcinoma, Squamous Cell; Cytoplasmic Granules; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Neoplasm Staging; Prognosis; Somatostatin

Keratin protein immunohistochemistry is a powerful diagnostic tool whose role has already been firmly established in many surgical pathology laboratories. Recent studies of the biology of keratin proteins have defined the heterogeneity of keratin protein expression among various epithelial tissues and their tumors and provide the basis for understanding the immunoreactivity of epithelial tumors with various keratin antibodies. Successful execution of the procedure requires attention to technical details such as the fixation of tissue, use of proteolytic enzymes such as trypsin for formalin-fixed tissues, and the choice of the appropriate antibody and controls. Broadly reactive polyclonal and monoclonal antibodies to keratins have been remarkably useful in identifying poorly differentiated and undifferentiated carcinomas. Monoclonal antibodies of restricted specificity and monospecific antibodies to keratin are under development and may prove helpful in defining the organ of origin of metastatic carcinomas. Keratin protein immunohistochemistry supplements existing information used by pathologists in diagnosis, and the immunohistochemical results should be interpreted in the light of the clinical findings, gross and microscopic pathology, and the results of any other special studies.

Topics: Animals; Antibodies; Antibodies, Monoclonal; Bone Neoplasms; Carcinoid Tumor; Carcinoma; Humans; Immunoassay; Keratins; Neoplasms; Sarcoma; Soft Tissue Neoplasms

A wide variety of human neoplasms were examined by immunocytochemical and ultrastructural techniques. In most, one intermediate filament (IF) type was expressed reflecting the tissue of origin. However, multiple classes of intermediate filaments were regularly found in a subgroup of these tumors. We chose to subdivide them into those with a complex or mixed growth pattern, and those which showed a more "monomorphic" histologic growth pattern. This latter group is the subject of this paper. Regular coexpression of cytokeratin and vimentin was observed in tumors of endometrial, thyroid, ovarian and renal origin, and coexpression of cytokeratin and neurofilament was observed in a subgroup of neuroendocrine tumors. Immunocytochemical/ultrastructural correlation demonstrated few, if any, observable intermediate filaments in tumors expressing only low molecular weight cytokeratin, whereas vimentin and neural filament characteristically were randomly dispersed or formed whorled bundles of cytoplasmic filaments. The potential diagnostic usefulness of these observations in surgical pathology is discussed.

Topics: Carcinoid Tumor; Carcinoma; Carcinoma, Small Cell; Cytoskeleton; Endocrine System Diseases; Female; Humans; Intermediate Filaments; Keratins; Kidney Neoplasms; Lung Neoplasms; Ovarian Neoplasms; Thyroid Neoplasms; Uterine Neoplasms; Vimentin

Topics: Carcinoid Tumor; Diagnosis, Differential; Humans; Keratins; Lung Neoplasms; Male; Middle Aged; Paraganglioma

Topics: Adult; Breast Neoplasms; Carcinoid Tumor; Carcinoma, Adenoid Cystic; Carcinoma, Lobular; Chromogranin A; Diagnosis, Differential; Female; Humans; Hysterectomy; Keratins; Neoplasms, Multiple Primary; Ovarian Neoplasms; Sex Cord-Gonadal Stromal Tumors; Synaptophysin; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

Topics: Adenocarcinoma; Carcinoid Tumor; Child; Chromogranin A; Common Bile Duct; Common Bile Duct Neoplasms; Diagnosis, Differential; Duodenum; Gallbladder; Humans; Keratins; Lymphoma; Male; Mucin-1; Neoplasm Invasiveness; Rhabdomyosarcoma; Stomach; Synaptophysin

Topics: Aged; Biomarkers; Carcinoid Tumor; Carcinoma, Endometrioid; Diagnosis, Differential; Female; Granular Cell Tumor; Humans; Hysterectomy; Keratin-7; Keratins; Krukenberg Tumor; Middle Aged; Mucin-1; Ovarian Neoplasms; Sertoli Cell Tumor; Sex Cord-Gonadal Stromal Tumors

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

We present clinicopathological and cytological findings of a well-defined breast mass in a patient with history of primary renal carcinoid tumor. Fine-needle aspiration (FNA) cytology showed monotonous tumor cells with plasmacytoid appearance arranged singly and in small clusters. Occasional tumor cells were arranged in acinar architecture resembling glandular differentiation. Tumor cells showed fine speckled chromatin. The unusual location for metastasis of this rare type of carcinoid tumor and overlapping cytological features with primary mammary carcinoma led to an erroneous preliminary cytological diagnosis of primary breast carcinoma with plasmacytoid features. Tumor cells in the corresponding cell block showed strong diffuse positivity for synapthophysin and pan-cytokeratin with weak focal positivity for chromogranin markers. These patterns of immunostaining were similar to the original renal carcinoid tumor. To the best of our knowledge, a few cases of carcinoid tumor metastatic to the breast have been reported in the literature and more than half of these cases were initially misdiagnosed as primary breast carcinoma causing unnecessary surgical treatment. This is a first reported case of metastatic renal carcinoid tumor into breast diagnosed with FNA biopsy. This report highlights the cytological features of well-differentiated neuroendocrine tumor (carcinoid tumor) and its potential diagnostic pitfalls.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Biopsy, Fine-Needle; Breast Neoplasms; Carcinoid Tumor; Chromogranins; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Middle Aged; Synaptophysin

A reliable diagnosis of small cell lung cancers (SCLC) is of high clinical relevance. We investigated whether immunocytology substantially improves the diagnostic accuracy of conventional cytology in diagnosing SCLC.. 162 carcinomatous specimens clinically suspected to originate from pulmonary neoplasms were investigated by cytology and immunocytology. Immunocytology was performed on smears using HEA125 and pancytokeratin antibodies as epithelial markers and MOC-1 as SCLC probe.. As histologically clarified, 114 specimens corresponded to pulmonary neoplasms (SCLC = 51; non-small cell lung cancer: NSCLC = 59; mixed SCLC/NSCLC = 2; carcinoid = 2), 48 to nonpulmonary adenocarcinomas. By conventional cytology tumor cells were clearly detected in 93 (57.4%) and suspected in another 43 (26.5%) cases (83.9% overall sensitivity). Considering SCLC samples, tumor cells were diagnosed or suspected in 36 (70.5%), not identified in 10 (19.6%), and misdiagnosed as hematological malignancy in 5 cases. Only 2 specimens were accurately diagnosed as SCLC. Using the epithelial antibodies all samples were identified as carcinomatous. MOC-1 stained all but one SCLC, both SCLC/NSCLC, and both carcinoids. One SCLC brush smear was MOC-1 negative, containing only squamous epithelium. 3 pulmonary adenocarcinomas stained falsely positive, all nonpulmonary carcinomas MOC-1 negative.. Immunocytology substantially improves the diagnostic accuracy of cytology in diagnosing SCLC with a diagnostic sensitivity of 98% and specificity of 97%.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoid Tumor; Carcinoma, Small Cell; Carcinoma, Squamous Cell; CD56 Antigen; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Lung; Lung Neoplasms; Predictive Value of Tests

Renal carcinoid tumors are exceedingly rare tumors that have been primarily documented as case reports in the literature. In this study, we report a series of 21 renal carcinoid tumors, with emphasis on histopathologic features and clinical outcomes. Patient age ranged from 27 to 78 years (average 52 y). The majority of specimens consisted of radical nephrectomies with or without associated lymph node dissection. Nine tumors were present in the left kidney and 10 were present in the right; location was not available for 2 specimens. No anatomic region of the kidney appeared to be preferentially involved. Twenty tumors were unifocal and ranged in size from 2.6 to 17 cm (average 6.4 cm), and 1 tumor presented as 2 nodules measuring 1 and 2.8 cm. Four patients had a documented history of a horseshoe kidney. Two patients had a history of renal calculi and 1 patient had a history of urothelial carcinoma 8 years prior. Presenting symptoms and clinical findings included back or flank pain (n=6/9), enlarging abdominal mass or fullness (n=2/9), hematuria (n=2/9), and anemia (n=1/9). Twelve patients had concurrent metastases at the time of initial surgery to sites including lymph nodes (n=11/12), liver (n=5/12), bone (n=1/12), and lung (n=1/12). One additional patient developed subsequent metastases to the liver within 6 months of surgery. Examination of the specimens identified carcinoid tumor with a variety of patterns including tightly packed cords and trabeculae with minimal stroma (n=17/21), trabecular growth with prominent stroma (n=4/21), focal solid nests (n=4/21), focal glandlike lumina (n=4/21). The border between tumor and normal kidney was sharply defined in most cases (n=16/21), although focal infiltration was noted in 5/21 cases. Extracapsular extension was documented in 11/21 (52%) cases. Calcifications were present in 5/21 cases. Mitotic activity, measured as mitoses per 10 high-power fields, ranged from 0 to 2 in most cases, with 1 case demonstrating up to 4 mitotic figures per single high-power field. Necrosis was absent in all cases. Immunostains were frequently positive for synaptophysin (n=18/20), chromogranin (n=13/20), Cam5.2 (n=14/16), and vimentin (n=12/15). CK7 was focally positive in a small subset of cases (n=3/18) and CK20 was positive in 1 case. TTF-1 and WT-1 were negative in all cases examined. Clinical follow-up was available on 15 patients and ranged from 3 months to 11 years. One patient died of disease at 8 months after surgery a

Topics: Adult; Aged; Biomarkers; Biomarkers, Tumor; Carcinoid Tumor; Chromogranins; Female; Humans; Keratins; Kidney Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Nephrectomy; Synaptophysin; Treatment Outcome; Vimentin

Topics: Adult; Biopsy, Fine-Needle; Carcinoid Tumor; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Lung; Lung Neoplasms; Mucin-1; Neoplasm Metastasis; Pulmonary Sclerosing Hemangioma; Radiography; Vimentin

CDX-2 is a highly sensitive and specific marker of intestinal epithelial cells and their neoplastic counterparts. CDX-2 status in pseudomyxoma peritonei (PMP) has been barely reported. The aim of this study was to investigate the clinicopathological features of 42 cases of PMP with a special emphasis on CDX-2.. All patients were treated by cytoreduction. Immunohistochemistry was performed for CDX-2, MUC-2, MUC-5AC, cytokeratin (CK) 7 and CK20. Statistical correlation was evaluated for age, sex, completeness of cytoreduction and histological subtype with overall and progression-free survival (OS and PFS). PMP consisted of 32 cases of disseminated peritoneal adenomucinosis and 10 cases of peritoneal mucinous carcinomatosis. The appendix evaluated in 25 cases showed two mucinous adenocarcinomas and 21 low-grade appendiceal mucinous neoplasms. CDX-2 was diffusely positive in 40 cases, with the remaining two cases being focally positive. All cases demonstrated diffuse reactions to CK20 and MUC-2, and variable reactions to MUC-5AC, while CK7 was variably positive in 38 cases. Five-year OS was 97%. Histological type was significantly correlated with PFS (P=0.02).. CDX-2 is diffusely and strongly positive in PMP. This is a useful marker to confirm an appendiceal origin of PMP, particularly when used in conjunction with CK7, CK20, MUC-2 and MUC-5AC.

Topics: Adult; Aged; Appendiceal Neoplasms; Biomarkers, Tumor; Carcinoid Tumor; CDX2 Transcription Factor; Disease-Free Survival; Female; Homeodomain Proteins; Humans; Immunohistochemistry; Keratin-20; Keratin-7; Keratins; Male; Middle Aged; Mucin 5AC; Mucin-2; Mucins; Neoplasms, Multiple Primary; Peritoneal Neoplasms; Prognosis; Pseudomyxoma Peritonei; Retrospective Studies; Survival Analysis; Trans-Activators

Topics: Adult; Biomarkers; Biomarkers, Tumor; Carcinoid Tumor; Carcinoma, Hepatocellular; Chromogranin A; Cytoplasmic Granules; Diagnosis, Differential; Female; Hemangioma; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Synaptophysin; Treatment Outcome

The aim of the present study was to evaluate the usefulness of immunohistochemical markers in the differential diagnosis of pulmonary neuroendocrine tumors with particular emphasis on the preservation of immunoreactivity in areas showing crush artifacts. Specimens from 9 carcinoid tumors (CTs) and 13 small cell carcinomas (SCCs) with crush artifact were stained with antibodies to Ki-67, chromogranin A, synaptophysin, and cytokeratin. The immunoreactivity was well preserved in the crushed areas. Ki-67 was expressed in the crushed areas of all SCCs. Reactivity was diffuse or at least present in 25% of the crushed areas. In contrast, the immunoreactive areas in CTs never exceeded 10%. Immunoreactivity for Ki-67, synaptophysin, chromogranin A, and cytokeratin is well preserved in tissue with crush artifacts and can be interpreted reliably. The diagnosis of SCC should be questioned if fewer than 25% of cells show reactivity for Ki-67.

Topics: Artifacts; Biopsy; Bronchoscopy; Carcinoid Tumor; Carcinoma, Small Cell; Chromogranin A; Chromogranins; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Ki-67 Antigen; Lung Neoplasms; Synaptophysin

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoid Tumor; Chromogranins; Disease-Free Survival; Humans; Keratins; Male; Prostatic Neoplasms; Synaptophysin; Treatment Outcome

Topics: Bronchial Neoplasms; Carcinoid Tumor; Chromogranin A; Chromogranins; Humans; Immunohistochemistry; Keratins; Lymph Node Excision; Lymphatic Metastasis; Neoplasm Staging; Pneumonectomy; Survival Analysis

The differential expression of cytokeratin (CK) 7 and 20 by carcinomas may help in determining the primary site of a metastatic tumour. The aim of this study was to extend the published data on CK7 and CK20 expression in epithelial neoplasms of the gastrointestinal tract by considering the degree of differentiation and including some unusual neoplasms.. Cases referred to the Armed Forces Institute of Pathology were studied prospectively for immunohistochemical expression of CK7 and CK20. Lesions from 105 patients were analysed. Adenocarcinomas of the upper gastrointestinal tract were positive for both CK7 and CK20 in 78% of cases; only poorly differentiated lesions were CK7-. Well-differentiated and moderately differentiated adenocarcinomas of the large intestine, including appendix, were CK7-/CK20+ in the great majority of cases, as were goblet cell carcinoids, but half of the poorly differentiated adenocarcinomas exhibited aberrant expression, as did most of the mixed goblet cell carcinoid/adenocarcinomas. All five high-grade neuroendocrine carcinomas were negative for both CK7 and CK20.. Not only the site but also the grade and histological type of a gastrointestinal carcinoma should be considered when assessing cytokeratin phenotype.

Topics: Adenocarcinoma; Carcinoid Tumor; Gastrointestinal Neoplasms; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Neoplasms, Multiple Primary; Prospective Studies

Carcinoid tumors and adenomas of the middle ear are rare neoplasms of indeterminate relationship to one another. Indeed, the literature is devoid of a large comprehensive series that evaluates the clinical, histologic, and immunophenotypic features of these tumors and their potential relationship. Forty-eight cases of middle ear adenoma between 1970 and 1995 were identified in the files of the Armed Forces Institute of Pathology. All cases were evaluated for cytomorphology and architectural pattern, in addition to their reactivity with various immunohistochemical reagents. Clinical follow-up was also obtained. A comprehensive review of the literature was performed with an eye toward correlating any distinct differences or similarities between carcinoid tumors and adenomas of the middle ear. The patients included 21 women and 27 men, aged 20 to 80 years (mean, 45.0 y). Patients experienced hearing loss, mass, and/or pain for a mean duration of 1.7 years. The mean tumor size was 0.8 cm, with six tumors extending beyond the middle ear. Histologically, the tumors were moderately cellular and unencapsulated, arranged in glandular, trabecular, and solid patterns composed of small cells with "salt and pepper" nuclear chromatin distribution. The tumor cells were immunoreactive with keratin, keratin 7, chromogranin, and human pancreatic polypeptide. All patients had surgery. No patients died with their disease (mean follow-up, 15.7 y). Eight patients developed recurrences that were treated surgically and were without evidence of disease at last follow-up (mean, 15.1 y). Our study and the review of the literature showed adenomas and carcinoid tumors of the middle ear to be essentially indistinguishable benign tumors. Middle ear adenoma most correctly describes their morphologic features and clinical behavior, although neuroendocrine adenoma of the middle ear may be a more accurate designation.

Topics: Adenoma; Adult; Aged; Aged, 80 and over; Carcinoid Tumor; Chromogranins; Diagnosis, Differential; Ear Neoplasms; Ear, Middle; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratin-7; Keratins; Male; Middle Aged; Neoplasm Recurrence, Local; Pancreatic Polypeptide; Phosphopyruvate Hydratase; Review Literature as Topic; S100 Proteins; Treatment Outcome; Vimentin

To report about a lung tumor that was a combination of typical carcinoid and adenocarcinoma.. The patient, a 71-year-old male, presented with a 2.5-cm pulmonary nodule that, microscopically, was a combination of an adenocarcinoma (tubular with clear cell features and bronchioloalveolar) and a typical carcinoid. Immunohistochemically, both components were positive for cytokeratin, but only the carcinoid component was positive for chromogranin and synaptophysin. In the range of neuroendocrine tumors of the lung, a combination with other histological types of carcinoma (squamous, adeno, large cell and pleomorphic) can be found with both small cell carcinoma and large cell neuroendocrine carcinoma, but is very rare with typical and atypical carcinoids.

Topics: Adenocarcinoma, Bronchiolo-Alveolar; Adenocarcinoma, Clear Cell; Aged; Biomarkers, Tumor; Carcinoid Tumor; Carcinoma, Non-Small-Cell Lung; Chromogranins; Humans; Keratins; Lung Neoplasms; Male; Neoplasm Proteins; Neoplasms, Multiple Primary; Synaptophysin

Twelve cases of carcinoid tumors of the thymus were reviewed in terms of clinicopathologic, histochemical, and immunohistochemical features and DNA ploidy patterns. The collective consisted of nine male and three female patients, aged 34 to 74 years, of whom five (42%) had symptoms. Eleven patients underwent surgical resection, and one with systemic metastases was autopsied. In the 11 resected patients, tumors had invaded surrounding structures in four cases, and mediastinal lymph node metastases were detected in six. Recurrence occurred in two of the resected patients (18%), and the 5-year survival rate was 82%. Histologically, all tumors showed an organoid growth pattern with delicate fibrovascular stroma. In addition, three tumors had unusual morphologic features such as combined features of carcinoid tumor and thymoma and solid growth pattern with occasional large tumor cells. Mitotic counts ranged from 1 to 14 per 10 high-power fields with a mean count of 4.9. Central necrosis within solid nests was observed in nine tumors. Classification of this series using the WHO histologic classification system resulted in categorization of all 12 tumors as atypical carcinoids. All tumors were positive for Grimelius staining and for cytokeratin. Immunohistochemical staining documented the presence of moderately to strongly positive neuroendocrine markers such as neuron-specific enolase, chromogranin A, synaptophysin, and neural cell adhesion molecule. No correlation between proliferative activity based on the Ki67 labeling index and prognosis or lymph node metastasis was found. Concerning DNA ploidy patterns, only one tumor with multiple lymph node metastases was considered to be aneuploid. In conclusion, although all of our cases were histologically classified as atypical carcinoid tumors of the thymus, most were diploid, and the patients enjoyed a relatively good prognosis.

Topics: Adrenocorticotropic Hormone; Adult; Aged; Carcinoid Tumor; Cholecystokinin; Chromogranin A; Chromogranins; DNA, Neoplasm; Female; Flow Cytometry; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Male; Middle Aged; Neural Cell Adhesion Molecules; Phosphopyruvate Hydratase; Ploidies; S100 Proteins; Silver Staining; Somatostatin; Survival Analysis; Synaptophysin; Thymus Neoplasms

Expression of cytokeratin (CK) 7 and 20 is commonly used to help distinguish adenocarcinomas from different sites. Thyroid transcription factor 1 (TTF-1) is a 38-kd protein, located primarily in the nucleus of type 2 pneumocytes and clara cells. TTF-1 has been shown to be present in a variety of lung and thyroid tumors and in pulmonary small-cell carcinomas. Carcinoid tumors from the lung and the gastrointestinal (GI) tract are histologically similar and thus are difficult to differentiate from each other based on histologic criteria. Pancreatic endocrine tumors (PET) have a similar histologic appearance to these other tumors. The purpose of this study was to determine the efficacy of differentiating these 3 groups of tumors by their expression of CK7, CK20, and TTF-1. Routinely processed paraffin-embedded tissue sections from 62 carcinoid tumors (lung, 16; gastrointestinal [GI] tract, 46) and 12 PETs were immunohistochemically stained for CK7, CK20, and TTF-1. The degree of expression in each tumor was graded as 1+ (1% to 10% of cells positive), 2+ (11% to 25%), 3+ (26% to 50%), and 4+ (>50%). The data were compared between tumor types and between carcinoid tumors from the various locations in the GI tract (stomach, 8; small intestine, 19; large intestine, 17; appendix, 2). CK7 was expressed in 10 (63%) of 16 pulmonary carcinoid tumors and only 5 (11%) of 46 GI carcinoid tumors (P <.001). Pancreatic endocrine tumors showed CK7 positivity in 6 (50%) of 12 cases, which was similar to the findings in lung carcinoids and significantly higher than in GI carcinoids (P <.01). CK20 was expressed in 0 (0%) of 16 pulmonary carcinoid tumors, in contrast to 24% and 33% of GI carcinoid tumors (P <.05) and PETs (P <.05), respectively. TTF-1 expression was highly specific for pulmonary carcinoid tumors. This peptide was present in 11 (69%) of 16 pulmonary carcinoid tumors and in only 1 (2%) of 46 and 0 (0%) of 12 GI carcinoid tumors (P <.001) and PETs (P <.001), respectively. A CK7(+)/CK20(-)/TTF-1(+) immunopanel result was moderately sensitive (sensitivity, 50%), and highly specific (specificity, 100%), for a diagnosis of pulmonary carcinoid tumor. CK7, CK20, and TTF-1 did not differ significantly between carcinoid tumors located in different sites of the GI tract. However, a trend was observed toward a lower prevalence of CK20 positivity in gastric tumors (P =.06) than in GI carcinoid tumors from the small intestine, colon, or appendix. Expression of CK7 and CK20, an

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoid Tumor; Diagnosis, Differential; Female; Gastrointestinal Neoplasms; Humans; Immunoenzyme Techniques; Insulinoma; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Nuclear Proteins; Thyroid Nuclear Factor 1; Transcription Factors

Topics: Carcinoid Tumor; Chromogranin A; Chromogranins; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Phosphopyruvate Hydratase; Serotonin; Skin Neoplasms

Topics: Carcinoid Tumor; Cauda Equina; Diagnosis, Differential; Humans; Keratins; Paraganglioma; Peripheral Nervous System Neoplasms; Sacrum

Two cases of pigmented thymic carcinoids are presented. The patients were two men, 32 and 47 years of age. The two patients were asymptomatic and the tumor was discovered on routine chest radiographic evaluation. The tumors were treated by surgical excision in both patients. Grossly, they presented as tan-white tumors without evidence of necrosis or hemorrhage or any visible pigmentation. Histologically, the tumors were characterized by a monotonous proliferation of tumor cells arranged in a trabecular or nesting pattern. The tumor cells showed moderate amounts of pale eosinophilic cytoplasm, round to oval nuclei, and inconspicuous nucleoli. Mitotic activity varied from three to eight per 10 high-power fields. In addition, both tumors showed prominent areas of intra- and extracellular dark pigment deposition. The pigment reacted positively with the Fontana-Masson stain and was negative for iron stain. Immunohistochemical studies performed in one case showed immunoreactivity of the tumor cells for chromogranin, Leu 7, and keratin. Synaptophysin and P53 immunostains were negative. Clinical follow-up was obtained in one patient who was alive and well 10 years after surgical resection. The presence of abundant melanin pigment in thymic carcinoids highlights an important pitfall for diagnosis in these tumors that should be taken into consideration in the evaluation of anterior mediastinal lesions.

Topics: Adult; Carcinoid Tumor; CD57 Antigens; Chromogranins; Humans; Immunohistochemistry; Keratins; Male; Melanins; Middle Aged; Thymus Neoplasms

The purpose of this study is to evaluate keratin expression in neuroendocrine cells and carcinoid tumor of the gastrointestinal tract and lung. Neuroendocrine cells in the lung and the gastrointestinal tract reacted with low-molecular keratin strongly, but not with high-molecular keratin. The low-molecular keratin expression of carcinoid tumor in the lung and the gastrointestinal tract, which varied in degree, were identical to that of neuroendocrine cells. Keratin 8 and 18 were found abundantly in neuroendocrine tumor and carcinoid tumor of the gastrointestinal tract, and in a lesser amount in carcinoid tumor of the lung, whereas keratin 19 was found in all cases with variable amounts. Based on these results, the combination of antibodies for several types of keratin is useful for examining keratin expression as a marker of epithelium in carcinoid tumor.

Topics: Adult; Biomarkers, Tumor; Carcinoid Tumor; Female; Gastrointestinal Neoplasms; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Middle Aged

This report describes a case of atypical carcinoid of the larynx with metastatic tumor to cervical lymph nodes showing features similar to paraganglioma. Immunohistochemically, both the primary and metastatic tumor were positive for epithelial membrane antigen, cytokeratin, neuron-specific enolase, chromogranin, synaptophysin, calcitonin and carcinoembryonic antigen. The sustentacular cells in pseudo-cell ball ("Zellballen") formations were shown by a positive S-100 marker. Electron microscopic analysis revealed numerous neuroendocrine granules measuring 150-250 nm in diameter. Clinical features, histological appearance, histochemical, immunohistochemical and ultrastructural findings, as well as differential diagnosis are discussed.

Topics: Aged; Calcitonin; Carcinoembryonic Antigen; Carcinoid Tumor; Chromogranins; Cytoplasmic Granules; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Lymphatic Metastasis; Male; Microscopy, Electron; Mucin-1; Neck; Paraganglioma; Phosphopyruvate Hydratase; S100 Proteins; Synaptophysin

We report three cases of neuroblastoma arising within the thymus of elderly patients. All tumors consisted of primitive neuroblasts showing focal gangliocytic differentiation within nests of neuropil. All stained for neuroendocrine markers but were negative for cytokeratins and for the MIC2 gene product. One tumor was associated with the syndrome of inappropriate secretion of antidiuretic hormone, an endocrinopathy we found in three of five case reports of thymic neuroblastoma in adults. Immunohistochemical stains confirmed production of antidiuretic hormone by this tumor. One patient died of progressive disease, one patient is disease free at 18 months, and the other patient died of unrelated causes, a spectrum that reflects the variable clinical behavior others have reported. The possible histogenesis of these purely neural tumors includes malignant transformation of a mediastinal teratoma, aberrantly located sympathetic ganglia, neuroectodermal cells native to the normal thymus, and precursors of thymic epithelial cells that have differentiated along neural lines.

Topics: Aged; Aged, 80 and over; Carcinoid Tumor; Chromogranins; Female; Humans; Immunohistochemistry; Inappropriate ADH Syndrome; Keratins; Male; Mediastinal Neoplasms; Microscopy, Electron; Neuroblastoma; Phosphopyruvate Hydratase; Synaptophysin; Thymus Gland; Thymus Neoplasms

A histologic and immunohistochemical study was performed to identify the histogenesis of solid cell nests (SCN), which were found incidentally in 11 thyroid glands obtained by surgery. Histologically, SCN consisted of small nests showing solid and cystic structures. Cystic features of SCN were found in 3 of the 11 cases (27%), with mucinous materials in their lumens. Some goblet cells were also present in three cases (27%). In one case, SCN were associated with lymphocyte aggregation. Immunohistochemical analysis using serial sections of the SCN showed that the cells comprising SCN were positive for calcitonin in 5 cases (45%), for carcinoembryonic antigen (CEA) detected using polyclonal antibody in 11 (100%), for CEA detected using monoclonal antibody in 3 (27%), for calcitonin gene related peptide in 2 (18%), for chromogranin A in 5 (45%), and for keratin in 11 (100%). These antigens were expressed concomitantly in the same SCN, but the number and distribution of the positive cells for the antigens were different for each antigen in the same SCN in each case. These findings strongly support the view that SCN are derived from the ultimobranchial body. In addition, the biologic function to produce the antigens may vary greatly in individual cells comprising SCN.

Topics: Adenoma; Adult; Calcitonin; Calcitonin Gene-Related Peptide; Carcinoembryonic Antigen; Carcinoid Tumor; Carcinoma, Papillary; Chromogranin A; Chromogranins; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucins; Thyroglobulin; Thyroid Neoplasms

Topics: Adult; Apudoma; Carcinoid Tumor; Follow-Up Studies; Humans; Keratins; Male; Phosphopyruvate Hydratase; Thymus Neoplasms

A carcinoid tumour occurred in the uterine fundus causing an enlargement (12-14 weeks size). The patient did not have the carcinoid syndrome, despite elevated urinary 5-hydroxyindole acetic acid levels. The tumour had a typical organoid pattern with argentaffin-positive cells. Whilst a metastasis from an occult primary lesion cannot be entirely excluded, it is felt that this is a primary tumour most likely arising from resident endocrine cells in the endometrium.

Topics: Aged; Aged, 80 and over; Carcinoid Tumor; Chromogranins; Female; Humans; Keratins; Uterine Neoplasms; Uterus

For a study of histogenesis of intestinal carcinoids a collection of 5 classical small intestinal carcinoids, 6 appendiceal carcinoids and 9 pheochromocytomas, were evaluated. The tumors were identified by routine morphology, silver staining and chromogranin immunocytochemistry and were then examined with regard to the expression of intermediate filaments of cytokeratin type. Eight different antisera identifying individual or combinations of cytokeratins were employed. All classical small intestinal carcinoids displayed cytokeratin immunoreactivity and an almost identical cytokeratin reaction was observed in the normal enterocytes of the small intestinal mucosa. Of the individual cytokeratin types, number 18 was most heavily expressed. The appendiceal carcinoids, like the pheochromocytomas, almost totally lacked a cytokeratin staining despite a positive reaction in the mucosa of the appendix. This, in agreement with some previous studies, indicates that the small intestinal carcinoids are histogenetically related to the epithelial cells of the intestinal mucosa, while the appendiceal carcinoids have a different histogenesis and are more like pheochromocytomas. The appendiceal carcinoid may represent a distinct type of intestinal paraganglioma. This offers one explanation for the different biological behavior of appendiceal carcinoids in comparison with the other intestinal carcinoids.

Topics: Adrenal Gland Neoplasms; Appendiceal Neoplasms; Carcinoid Tumor; Humans; Immunohistochemistry; Intestinal Mucosa; Intestinal Neoplasms; Intestine, Small; Keratins; Pheochromocytoma; Staining and Labeling

A case of primary hepatic carcinoid tumor was recently encountered, which was argyrophil and showed positive reactions to serotonin, gastrin and pancreatic peptide in an immunohistochemical hormonal study. The tumor had unusual morphologic features. The neoplastic cells had a signet-ring cell appearance, similar to the signet-ring cells normally seen in mucin-producing adenocarcinoma. Ultrastructural and immunohistochemical studies revealed the formation of the signet-ring cells to have been caused by the presence of cytoplasmic inclusions consisting of cytokeratins. Further investigation, using eight monoclonal antibodies recognizing cytokeratins of different molecular weights, showed the accumulated cytokeratins to be of low and medium molecular weights. The morphologic observations in this unusual case of hepatic carcinoid tumor are described and reported cases with similar features, for which we propose the term "signet-ring cell carcinoid," are reviewed.

Topics: Adult; Carcinoid Tumor; Female; Humans; Immunohistochemistry; Inclusion Bodies; Keratins; Liver Neoplasms

The expression patterns of basement membrane components and keratin intermediate filament proteins were studied in normal human bronchial epithelium and 56 lung carcinomas using monoclonal antibodies to laminin, type VII collagen and the individual keratins 14, 16, 17 and 18. In normal lung, laminin and type VII collagen were present between the epithelium and the lamina propria of bronchi and bronchioles. Keratin 14 was expressed in the basal cells, keratin 17 in the basal and some suprabasal cells and keratin 18 in the columnar cells of the bronchi and bronchioles. Keratin 16 was not present in normal bronchial epithelium. Laminin was found in all subtypes of lung carcinoma, but type VII collagen was present only in squamous cell carcinomas, where it showed a reduction in expression with decreasing differentiation. Type VII collagen was not identified in adenocarcinomas, small cell carcinomas or carcinoids. Antibodies to basal cell keratins 14 and 17 also displayed positivity only in squamous cell carcinomas, although no correlation with the degree of differentiation could be observed. Keratin 16 appeared to be a marker of the squamous phenotype, rather than of hyperproliferation. The keratin 18 marker for columnar epithelial cells showed a reaction pattern opposite to that of the basal cell keratins, being extensively present in adenocarcinomas, small cell carcinomas and carcinoids, with less expression in squamous cell carcinomas. This study shows a correlation between the presence of type VII collagen and the basal cell keratins 14 and 17, and a negative correlation between these components and keratin 18. These findings are likely to be useful in identifying lung cancer subtypes.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoid Tumor; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Collagen; Humans; Immunoenzyme Techniques; Keratins; Laminin; Lung Neoplasms

Carcinoid tumors of the lung in 10 patients were treated surgically and both the clinicopathological manifestations and immunohistochemistry were examined in detail. Five were central carcinoid tumors, located in the main, lobar or segmental bronchus and five were peripheral carcinoid tumors, located in the subsegmental bronchus or beyond. Histologically, eight of the tumors were typical carcinoid tumors, one was an atypical carcinoid tumor, and one a carcinoid tumorlet. Three growth types were also established: polypoid type, iceberg type and intrapulmonary type. The central carcinoid tumors belonged either to the polypoid type or iceberg type, while the peripheral carcinoid tumors were of the intrapulmonary type. Both the iceberg and intrapulmonary types may invade the peribronchial or parenchymal tissues more frequently than does the polypoid type. Immunohistochemically, argyrophilia and neuron-specific enolase (NSE) were detected in all the tumors examined and six stained for polypeptide hormones such as adrenocorticotropic hormone (ACTH) and/or pancreatic polypeptide (PP). Of these, five had epithelial markers such as keratin, epithelial membrane antigen (EMA) and/or carcino-embryonic antigen (CEA). These findings suggest that a carcinoid tumor of the lung originates from primitive multipotential stem cells such as those of a neuroendocrine or epithelial nature.

Topics: Adrenocorticotropic Hormone; Adult; Aged; Antigens, Neoplasm; Carcinoembryonic Antigen; Carcinoid Tumor; Female; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Pancreatic Polypeptide; Phosphopyruvate Hydratase

Two cases of carcinoid tumors, considered to be probably hepatic in origin, occurring in a 53-year-old man and a 69-year-old woman are reported. In both cases no endocrine syndrome appeared, and an alternative primary source of the tumor was not found in case two, despite an intensive search at operation. The neoplasms in both cases were soft, firm, brown-pink and well-encapsulated. They were composed of small uniform cells, that had distinct borders and grew in insular, nests, trabeculae and strands that were separated by a delicate fibrous stroma. Stains of argentaffin and argyrophil showed strong positivity in both cases. The immunohistochemical and ultrastructural studies all demonstrated characteristics of a carcinoid. The postoperative recovery was good. They have remained well 5 years later in case 1 and 3 years in case 2 after surgical treatment. Literature concerning this rare condition is also reviewed.

Topics: Aged; Carcinoid Tumor; Female; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Middle Aged

A case of primary carcinoid tumor of the liver with striking morphologic and electron microscopic features is reported. Conventional histologic examination showed a prominent paranuclear clear zone in numerous tumor cells. By electron microscopic examination, this clear zone corresponded to a paranuclear mass of intermediate filaments admixed with neurosecretory granules and other cytoplasmic organelles.

Topics: Aged; Antigens, Neoplasm; Carcinoembryonic Antigen; Carcinoid Tumor; Chromogranins; Cytoplasmic Granules; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Membrane Glycoproteins; Microscopy, Electron; Mucin-1; Organelles; Phosphopyruvate Hydratase

Topics: Antibodies, Monoclonal; Carcinoid Tumor; Humans; Keratins; Orbital Neoplasms

Based on our review of 35 cases and the literature, we found the spectrum of pulmonary neuroendocrine (NE) tumors to be too broad to fit into the traditional three-category classification scheme of typical carcinoid (TC), atypical carcinoid (AC), and small-cell lung carcinoma (SCLC). We found that a spectrum of high- and low-grade tumors exist between TC and SCLC and that in the past many of these tumors have been called AC. We chose to adhere to Arrigoni's definition of AC, as his original criteria characterized a low-grade tumor. For the higher grade non-small-cell tumors (NSCLC), we propose a fourth category of large-cell neuroendocrine carcinoma (LCNEC), which is characterized by: (a) light microscopic NE appearance; (b) cells of large size, polygonal shape, low nuclear-cytoplasmic ratio (N:C), coarse nuclear chromatin, and frequent nucleoli; (c) high mitotic rate [greater than 10/10 high-power fields (HPF)] and frequent necrosis; and (d) NE features by immunohistochemistry (IHC) or electron microscopy (EM). Thus, after deciding that a pulmonary NE tumor is high grade, the major diagnostic issue is separation of LCNEC from SCLC. This distinction is based not only on cell size, but on a variety of morphologic features. We studied 20 TC, six AC, five LCNEC, and four SCLC and characterized the clinical, light microscopic, EM, IHC, and flow cytometric features of each type of tumor. We did not find any advantage to IHC, EM, or flow cytometry over light microscopy in the subclassification or prediction of prognosis; however, these methods were useful in characterizing these four types of pulmonary NE tumors and in demonstrating their NE properties. LCNEC must be distinguished from a fifth category pulmonary NE tumor: NSCLC with NE features in which NE differentiation is not evident by light microscopy and must be demonstrated by EM or IHC. Although the prognosis of LCNEC appears to be intermediate between AC and SCLC, larger numbers of patients will be needed to demonstrate significant differences in survival.

Topics: Adrenocorticotropic Hormone; Adult; Aged; Antigens, Differentiation; Bombesin; Calcitonin; Carcinoembryonic Antigen; Carcinoid Tumor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; CD57 Antigens; Chromogranins; Female; Flow Cytometry; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Membrane Proteins; Microscopy, Electron; Middle Aged; Synaptophysin; Terminology as Topic

A case of a possible primary carcinoid tumor of the skin in a 40-year-old man is presented. The neoplasm was diagnosed as consistent with carcinoid tumor on the basis of conventional light microscopy, immunohistochemical studies, and electron microscopy. Workup revealed no evidence of carcinoid tumor elsewhere. Metastases to the skin from internal carcinoid tumors are uncommon, but presumed primary carcinoid tumors that arise in the skin are extremely rare; only three cases have been found in the English-language literature.

Topics: Adult; Biopsy; Carcinoid Tumor; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Skin; Skin Neoplasms

A case of neuroendocrine lung tumor located beneath the pleura in a 71-year-old woman is reported. At autopsy, the tumor was found to have metastasized to the bones and liver without involving the hilar lymph nodes. Histologically, the tumor cells at the primary site and in the liver metastasis exhibited a carcinoid-like organoid structure, whereas pleomorphic giant cells were noted in the bone metastasis. The argyrophilic tumor cells were immunoreactive for neuron-specific enolase, chromogranin A, serotonin, calcitonin, calcitonin gene-related peptide, gastrin-releasing peptide, neuropeptide Y, gastrin, pancreatic polypeptide, glicentin, the alpha-subunit of human chorionic gonadotropin, keratin, epithelial membrane antigen, Leu M1 and carcinoembryonic antigen. Electron microscopy revealed abundant neurosecretory granules in the cytoplasm. This was considered to be a rare case of neuroendocrine lung tumor showing carcinoid-like histology at the primary site and large-cell transformation in bone metastasis.

Topics: Aged; Autopsy; Bone Neoplasms; Calcitonin; Calcitonin Gene-Related Peptide; Carcinoembryonic Antigen; Carcinoid Tumor; Cell Transformation, Neoplastic; Chorionic Gonadotropin; Chromogranin A; Chromogranins; Female; Giant Cell Tumors; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Membrane Glycoproteins; Microscopy, Electron; Mucin-1; Phosphopyruvate Hydratase; S100 Proteins; Serotonin

A primary carcinoid tumour of the breast in a 66-year-old man was diagnosed by fine-needle aspiration cytology. The nature of the lesion was proved by histochemical and immunocytochemical studies. The importance of a conclusive diagnosis is discussed and the value of immunocytochemical analysis as an aid to cytomorphologic diagnosis is demonstrated.

Topics: Aged; Biomarkers, Tumor; Biopsy, Needle; Breast Neoplasms; Carcinoid Tumor; Cytoplasmic Granules; Humans; Keratins; Male; Neoplasm Proteins; Phosphopyruvate Hydratase

A bronchial carcinoid with globular intracytoplasmic inclusions is reported. The inclusions stain brown with Grimelius silver impregnation and some show distinct immunoreactivity for chromogranin A. Tumour cells stain positively with antisera to neuron specific enolase, chromogranin A and not with antisera against ACTH, somatostatin or S-100 protein. The cells show distinct immunoreactivity for cytokeratins and vimentin, which is particularly intense in the intracytoplasmic inclusions. Desmin and glial fibrillary acidic protein are absent. Ultrastructural analysis reveals that the inclusions are composed of aggregates of filaments of 8-10 nm of diameter, intrapping a few neurosecretory granules. Immunohistochemical and ultrastructural data support the hypothesis that the inclusions are composed of intermediate filaments, whose metabolism and synthesis have somehow been deranged.

Topics: Bronchial Neoplasms; Carcinoid Tumor; Cell Nucleus; Humans; Immunohistochemistry; Inclusion Bodies; Keratins; Microscopy, Electron; Staining and Labeling; Vimentin

The immunohistochemical expression of intermediate filaments was investigated in 56 carcinoid tumors from 50 cases including 31 rectal and 25 non-rectal sites. Cytokeratin was the most frequently expressed in 55 of the tumours. Only one tumour of the stomach was negative for cytokeratin. Neurofilament (68 kd and 160 kd) was positive in 25 (44.6%) tumours with no preferential pattern of expression in particular tumours. Vimentin was positive in 18 out of the 31 rectal carcinoids (58%), and 3 of the 25 non-rectal carcinoids (12%). There was a significant difference in vimentin immunoreactivity between rectal and non-rectal carcinoids. The coexpression of cytokeratin and neurofilament was 44.6% and that of cytokeratin and vimentin was 37.5%. The coexpression of all three types of intermediate filament was 35.5% in rectal carcinoids, but 8% in non-rectal carcinoids. The present study revealed coexpression of cytokeratin, neurofilament and vimentin in carcinoids and an especially high incidence of vimentin expression in those of rectal origin.

Topics: Carcinoid Tumor; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Neurofilament Proteins; Rectal Neoplasms; Vimentin

Occurrence and expression of cytokeratins were studied by the immunoperoxidase-antiperoxidase (PAP) technique in formalin-fixed, paraffin embedded material from 18 cases of carcinoid tumours of the gastrointestinal tract. Polyclonal antikeratin for wide spectrum screening was detected in 12 cases; low molecular weight cytokeratins, C19 and CAM5.2 were positive in majority of the cases whereas antikeratins for high molecular weight were negative in all. Similar positive immuno-reactivity with antibodies to cytokeratins were detected in the surrounding epithelial cells. These results suggest that carcinoids of the gastrointestinal tract originate from the endodermal stem cell and differentiates along one or more directions, and the immunohistochemical findings depend upon the direction of their differentiation.

Topics: Appendiceal Neoplasms; Biomarkers, Tumor; Carcinoid Tumor; Gastrointestinal Neoplasms; Humans; Ileal Neoplasms; Immunoenzyme Techniques; Keratins; Rectal Neoplasms; Retrospective Studies; Stomach Neoplasms

In order to compare histologic subtypes and endocrine profiles, immunohistochemical and silver stains were performed on 120 appendiceal carcinoids. Forty-three were predominantly insular; 21 were mixed insular, glandular, and trabecular; 33 were goblet cell; 17 were tubular; and five were clear cell carcinoids. Insular, mixed, and clear cell carcinoids were generally diffusely argentaffin and positive for chromogranin, neuron-specific enolase (NSE), and serotonin. Occasional tumors of insular or mixed patterns had scattered cells that stained weakly for glucagon, calcitonin, adrenocorticotrophic hormone (ACTH), somatostatin, cholecystokinin (CCK), human pancreatic polypeptide (HPP), or gastrin. Most had S-100-positive sustentacular cells. Less than half were positive for carcinoembryonic antigen (CEA). Many were cytokeratin-positive, but often focally. Goblet cell carcinoids contained few endocrine cells, but these were strongly argentaffin and positive for serotonin in nearly all, and positive for HPP in almost a third. Tubular carcinoids lacked argentaffinity and serotonin but were diffusely and strongly positive for glucagon. All goblet cell and tubular carcinoids were diffusely positive for CEA and cytokeratin. Somatostatin stained strongly in a single tumor, which had psammoma bodies and was in a patient with neurofibromatosis. In all groups, argentaffinity correlated with serotonin positivity, and argyrophilia with chromogranin positivity, although the latter was somewhat more sensitive. We conclude that among appendiceal carcinoids, the endocrine content varies according to histologic subtype.

Topics: Adrenocorticotropic Hormone; Appendiceal Neoplasms; Carcinoembryonic Antigen; Carcinoid Tumor; Cholecystokinin; Chromogranins; Diagnosis, Differential; Follow-Up Studies; Gastrins; Glucagon; Humans; Immunohistochemistry; Keratins; Pancreatic Polypeptide; Phosphopyruvate Hydratase; S100 Proteins; Serotonin; Somatostatin

The clinical, microscopic, immunohistochemical and ultrastructural features of 7 gastrinomas and 1 combined carcinoma-carcinoid tumor were evaluated. The tumors were located in the pancreas or duodenal wall in 6 cases, and on extragastro-enteropancreatic sites in 2 (liver or peripancreatic lymph node). All patients had the Zollinger-Ellison syndrome, 3 of them with additional bleeding and 1 with diarrhea. One patient with gastrinoma had additional tumors characteristic of the MEN-I syndrome. Immunohistochemistry showed gastrin and neuron-specific enolase-positivity in all of the tumors. Somatostatin was found in 4 cases, and single cell glucagon, pancreatic polypeptide. S-100 protein, keratin as well as carcino-embryonic antigen positivity in another few. Additional hormone production did not appear to be connected with biological behaviour of the tumors or with the clinical symptoms.

Topics: Adolescent; Adult; Aged; Carcinoembryonic Antigen; Carcinoid Tumor; Duodenal Neoplasms; Female; Gastrins; Glucagon; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Pancreatic Neoplasms; Pancreatic Polypeptide; Phosphopyruvate Hydratase; S100 Proteins; Somatostatin; Zollinger-Ellison Syndrome

A composite tumor of the gastric antrum composed of areas of adenocarcinoma and poorly differentiated carcinoid is described, with histochemical and immunohistochemical documentation of endocrine and nonendocrine differentiation. The neoplasm maintained a composite architecture both within the site of origin and in lymph node metastases. The adenocarcinoma displayed a predominantly tubular architecture with focal sheets of clear cells. The poorly differentiated carcinoid was argyrophilic, chromogranin immunoreactive, and focally serotonin immunoreactive, and contained keratin intermediate filaments in a distinctive distribution suggestive of endocrine differentiation. Among the tumors of the carcinoma-carcinoid spectrum, the composite tumor is less common than either carcinomas with interspersed endocrine cells or carcinoids with interspersed nonendocrine cells.

Topics: Adenocarcinoma; Carcinoid Tumor; Chromogranins; Humans; Immunohistochemistry; Intermediate Filaments; Keratins; Male; Middle Aged; Stomach Neoplasms

The histological, histochemical and immunohistochemical features of twenty gastrointestinal carcinoid tumours are presented. Histologically, the foregut and hindgut carcinoids showed trabecular pattern and midgut carcinoid tumours usually showed insular type of growth. Histochemically, using the silver stains by the Grimelius and Masson-Fontana techniques, most (18 cases) were argyrophilic and 8 were argentaffin positive. Two appendiceal carcinoids were non-reactive. Mucin positivity was noted in a case of mucin producing carcinoid of the appendix. Immunohistochemistry for wide spectrum keratin, cytokeratin PKK1, carcinoembryonic antigen, neuron-specific enolase, neurofilament and S-100 protein revealed epithelial and neural characteristics of carcinoid tumour cells. Wide spectrum keratin was positive in 12 while cytokeratin PKKI was negative in all. Carcinoembryonic antigen positivity was noted in 8 cases. Neuron-specific enolase immunoreactivity was seen in 18 cases whereas neurofilament was negative. S-100 protein positive cells were observed in close contact with and/or intermingled with tumour cells but the tumour cells themselves were negative. Immunoreactivity for somatostatin was seen in 8 cases, glucagon in three, and corticotrophin, insulin and gastrin in one case each. More than one hormone expression was noted in three cases, one each of gastric, appendiceal and rectal carcinoid tumours. These findings suggest that carcinoid tumours may develop from an uncommitted cell native to the site of tumour and differentiates along one or more directions, and the immunohistochemical findings and secretory profile of these tumour cells depend upon the direction of their differentiation.

Topics: Carcinoembryonic Antigen; Carcinoid Tumor; Digestive System; Gastrointestinal Hormones; Gastrointestinal Neoplasms; Histocytochemistry; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Phosphopyruvate Hydratase; S100 Proteins

Topics: Adult; Aged; Bronchial Neoplasms; Carcinoid Tumor; Chorionic Gonadotropin; Female; Humans; Keratins; Male; Middle Aged; Phosphopyruvate Hydratase; Somatostatin

Lung cancers were investigated for their heterogeneity as expressed by their immunoreactivity for cytokeratins and neurofilament proteins, as well as for the neuroendocrine differentiation antigen MOC-1. Using broadly cross-reacting antibodies, cytokeratins were detected in nearly all cases of lung carcinomas. Keratinization could be detected only in cases of moderately to well-differentiated squamous cell carcinoma (SQC) using a monoclonal antibody to cytokeratin 10, while a monoclonal antibody reactive with cytokeratin 18, and specific for glandular epithelia, reacted with adenocarcinomas, small cell lung carcinomas (SCLC), and lung carcinoids. In SQC this antibody could detect non-squamous cell differentiation, showing increasing numbers of positive cells with decrease of histologically detectable SQC differentiation. Cells positive for neurofilaments were demonstrated in some of the poorly differentiated SQCs and in some of the cases of SCLC, possibly representing the variant type of SCLC. Also in some of the lung carcinoids neurofilament proteins were present, colocalizing with cytokeratins. MOC-1 was present in all SCLC and lung carcinoids. This antibody could also detect neuroendocrine differentiation in all combined small cell carcinomas, in one poorly differentiated adenocarcinoma, and in about 30% of the poorly differentiated SQCs. Therefore, lung cancer heterogeneity can be detected using a panel of well-defined antibodies to intermediate filaments in combination with the MOC-1 antibody. The use of these antibodies in diagnosis can have prognostic significance and can lead to a more selective therapeutic approach.

Topics: Adenocarcinoma; Antibodies; Antigens, Neoplasm; Carcinoid Tumor; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cross Reactions; Cytoskeleton; Histocytochemistry; Humans; Immunoenzyme Techniques; Intermediate Filaments; Keratins; Lung Neoplasms

Paraffin sections of formalin-fixed tumor samples from 26 patients with neuroendocrine (Merkel cell) carcinoma of the skin (NECS) were studied immunohistochemically with three monoclonal antibodies to low molecular weight keratin (MAB-K) and with antibodies to leukocyte common antigen (LCA), neurofilament (NF), neuron-specific enolase (NSE), S100 protein (S100), and chromogranin (CGN), to investigate the relative diagnostic value of these antibodies. Samples from 20 lymphomas, 10 non-oat cell undifferentiated carcinomas, 10 oat cell carcinomas, and 10 melanomas served as controls. Keratin was found in 25 of the 26 NECS and in all undifferentiated and oat cell carcinomas. A ball-like immunostaining for keratins, resembling an inclusion body was seen only in cases of NECS and some carcinoids. Neurofilament, NSE, and CGN were expressed by fewer NECS than was keratin and all NECS were negative for LCA and S100. None of the lymphomas and melanomas contained detectable keratin, NF, NSE, or CGN. Only the lymphomas stained with LCA. Only the melanomas were S100-positive. It is concluded that keratin is the most useful single discriminating marker in the separation of neuroendocrine (Merkel cell) carcinoma of the skin from lymphoma, melanoma and, when the characteristic inclusion-like pattern is seen, from metastatic oat cell carcinoma.

Topics: Adult; Aged; Antibodies, Monoclonal; Carcinoid Tumor; Carcinoma; Carcinoma, Small Cell; Diagnosis, Differential; Female; Gastrointestinal Neoplasms; Histocytochemistry; Humans; Immunochemistry; Keratins; Lung Neoplasms; Lymphoma; Male; Melanoma; Microscopy, Electron; Middle Aged; Nerve Tissue Proteins; Skin Neoplasms

Thirty-four gastroenteropancreatic (GEP) neuroendocrine tumors were evaluated for expression of epithelial (keratin, carcinoembryonic antigen [CEA] and neuroendocrine (neuron-specific enolase, chromogranin, bombesin) markers, and results were correlated with histologic patterns and histochemical staining. Tumors of mixed pattern (insular or trabecular with glandular areas) predominated. CEA localization corresponded to staining for mucin, with polarized apical or lumenal staining in glandular areas. Four trabecular midgut carcinoids, however, revealed diffuse cytoplasmic staining for CEA. Staining for keratin proteins was present in 68% of tumors. Bombesin immunoreactivity was demonstrated in 60% of GEP neuroendocrine tumors, indicating that bombesin positive metastatic tumors may not be predominantly of pulmonary origin, as previously suggested. Chromogranin was a sensitive marker for identifying normal gastrointestinal neuroendocrine cells that were not demonstrated by staining for neuron-specific enolase. Chromogranin was present in most neuroendocrine tumors, but was absent from three of five rectal carcinoids in keeping with the distinctive profile of hormonal and silver staining in these tumors. All GEP neuroendocrine neoplasms expressed both neuroendocrine and epithelial markers, supporting their derivation from endodermal epithelium.

Topics: Bombesin; Carcinoembryonic Antigen; Carcinoid Tumor; Chromogranins; Digestive System; Gastrointestinal Neoplasms; Humans; Keratins; Nerve Tissue Proteins; Pancreas; Pancreatic Neoplasms; Phosphopyruvate Hydratase; Staining and Labeling

The authors assessed whether distinct patterns for keratin could be demonstrated in 10 adenocarcinomas, 10 carcinoids, and 4 mesotheliomas by an immunoperoxidase reaction using 3 polyclonal and 3 monoclonal antibodies to keratin. When color development in diaminobenzidine (DAB) was allowed to proceed for less than 2 minutes, distinct patterns for keratin could be demonstrated using two polyclonal and two monoclonal antibodies; these were plasma membrane and/or web-like in the adenocarcinomas, punctate or crescentic in the carcinoids, and perinuclear in the mesotheliomas consisting of tumor cells with abundant cytoplasm. Immunoelectron microscopy using protein A colloidal gold confirmed these results. When color development in DAB was allowed to proceed for more than 2 minutes, only diffuse staining was seen. The distinct patterns of immunostaining for keratin obtained with the shorter color development were helpful in differentiating adenocarcinomas, carcinoids, and mesotheliomas.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoid Tumor; Electrophoresis, Polyacrylamide Gel; Female; Humans; Immunoenzyme Techniques; Keratins; Mesothelioma

Topics: Carcinoid Tumor; Electrophoresis, Polyacrylamide Gel; Female; Histocytochemistry; Humans; Intermediate Filaments; Keratins; Lung Neoplasms; Microscopy, Electron; Middle Aged

Twelve cases of gastrointestinal neuroendocrine tumors, including eight carcinoids and four pancreatic islet cell tumors or their metastases, were immunohistochemically analyzed for the expression of different types of intermediate filament proteins. All of the tumors showed cytokeratin positivity in immunostaining, and the Western blotting technique revealed 45- and 52-kilodalton cytokeratins in carcinoid tumors. Three of the islet cell tumors, but none of the carcinoid tumors, showed, in addition, varying numbers of neurofilament-positive tumor cells when evaluated with rabbit and mouse monoclonal antineurofilament antibodies. The presence of only the 70-kilodalton neurofilament and cytokeratin polypeptides in an islet cell tumor was revealed also by using the Western blotting technique. On the other hand, both fetal and adult pancreatic islet cells showed only cytokeratin positivity. Neurofilament-positive epithelial cells were not found in normal small intestines either. The results show epithelial characteristics in normal gastrointestinal neuroendocrine cells and neuroendocrine tumors by their expression of cytokeratin. In addition, some islet cell tumors display the 70-kilodalton neurofilament protein which suggests the acquisition of a new type of intermediate filament during the neoplastic change.

Topics: Adenoma, Islet Cell; Carcinoid Tumor; Cytoskeleton; Gastric Mucosa; Gastrointestinal Neoplasms; Humans; Intestinal Mucosa; Keratins; Pancreas; Zollinger-Ellison Syndrome

Two cases of breast tumors with a uniform solid carcinoid pattern and argyrophilic dense-core granules were analyzed by immunohistochemistry in order to compare their characteristics with known features of other carcinoid tumors and ordinary breast carcinomas. The tumors were positive for keratin-type intermediate filaments, neuron-specific enolase and alpha-chain of human chorion gonadotropin but negative for vimentin and S-100 protein. Laminin was found only in a rim between tumor cell islands and stroma but not among the cells. It is concluded that these tumors are histologically, ultrastructurally and immunohistochemically similar to other carcinoid tumors. The present results suggest that both breast carcinoids and carcinomas may have a common precursor in the mammary secretory unit.

Topics: Aged; Breast Neoplasms; Carcinoid Tumor; Carcinoma; Chorionic Gonadotropin; Diagnosis, Differential; Female; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Keratins; Laminin; Middle Aged; Phosphopyruvate Hydratase; Staining and Labeling

Intermediate filaments (IF) are ubiquitous cytoplasmic structures which, by virtue of their cell- and tissue-type-specific characteristics, are widely used as markers of tissue derivation and as differential diagnostic aids in surgical pathology. In contradistinction to other IFs, vimentin filaments, characteristic of mesenchymal cells, may be co-expressed with other cell-type specific IFs--cytokeratin filaments, desmin filaments, glial filaments and neurofilaments--in some tumor cells, embryonic cells, and cells in vitro. In this study we describe a novel type of IF co-expression which does not involve vimentin-filaments, viz. the presence of both cytokeratin filaments and neurofilaments in human bronchial carcinoid tumor cells.

Topics: Bronchial Neoplasms; Carcinoid Tumor; Cytoskeleton; Electrophoresis, Polyacrylamide Gel; Fluorescent Antibody Technique; Frozen Sections; Humans; Keratins; Microscopy, Fluorescence; Peptides

One hundred and twenty seven cases of lung tumors were studied by the immunoperoxidase technique for the presence of CEA and beta-HCG. Twenty-nine of these tumors were additionally stained for keratin and SP1, CEA and SP1 could be demonstrated in 80% of the studied cases, while beta-HCG was found in only 9%. SP1 revealed an almost identical staining pattern to CEA and keratin was found only in squamous cell carcinomas. The tissue positivity of none of these three markers correlated with tumor size, lymphnodal involvement or histological type.

Topics: Adenocarcinoma; Aged; Bronchial Neoplasms; Carcinoembryonic Antigen; Carcinoid Tumor; Carcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Chorionic Gonadotropin; Female; Histocytochemistry; Humans; Keratins; Lung Neoplasms; Male; Middle Aged; Pregnancy Proteins; Pregnancy-Specific beta 1-Glycoproteins

A bronchial P cell carcinoid, which was negative for all hormones immunocyto chemically tested, showed a globular intracytoplasmic inclusion in almost every cell. The inclusions were not clearly distinguishable using the haematoxylin- eosin- safran procedure; they were best demonstrated with the Masson trichrome stain and the Grimelius technique and were easily detected in 1 micron thick Epon sections as target-like structures. On electron microscopy, they were found to be composed of filamentous aggregates entrapping a few endosecretory granules, which showed degenerative changes. The filaments, 8-10 nm in diameter, lacked any periodicity; they were randomly dispersed in the central area and arranged in broken concentric swirls at the periphery of the inclusions. The globules lacked the tinctorial properties of amyloid, but showed a strong immunostaining for keratin-like proteins. A systematic investigation of 12 APUDomas of bronchial or duodenopancreatic origin, using both light and electron microscopy, identified a few filamentous bodies in one case, a somatostatin cell tumour of ampulla of Vater. In both cases, the structures appeared similar to those previously reported in growth hormone cell pituitary adenomas as well as in a few bronchial or gut carcinoids. Whatever their nature, morphological data suggest that they are related to abnormalities in the secretory function, involving the Golgi apparatus, the endosecretory granules and the microtubular microfilamentous system.

Topics: Adult; Ampulla of Vater; Apudoma; Bronchial Neoplasms; Carcinoid Tumor; Common Bile Duct Neoplasms; Duodenal Neoplasms; Female; Humans; Immunoenzyme Techniques; Inclusion Bodies; Insulinoma; Keratins; Pancreatic Neoplasms; Protein Precursors

Occurrence and distribution of cytokeratin, neuron specific enolase (NSE) and actin were studied by the immunoperoxidase-antiperoxidase (PAP)-technique using specific antibodies in formalin-fixed, paraffin-embedded material from 6 cases of neurogenic appendicopathy with numerous endocrine cells in the mucosal stroma (SEC), 5 cases of microcarcinoidosis of the stomach, 12 gastrointestinal carcinoids and 4 bronchial carcinoids. Cytokeratin was detectable in all tumor cells. In addition, the epithelial endocrine cells (EEC) and the SEC of intestinal origin were cytokeratin positive. EEC, SEC and cells of microcarcinoids and carcinoids showed a positive immunoreactivity with antibodies to NSE, whereas actin antibodies did not reveal significant staining of these cells. These results strongly suggest that carcinoids of the gastrointestinal tract originate from SEC that have migrated downwards into the stroma from the epithelial layer (" Endophytie " according to Feyrter ).

Topics: Carcinoid Tumor; Gastrointestinal Neoplasms; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins

We report a case of primary carcinoid of the kidney. The neoplasm had a trabecular growth pattern and was argyrophil positive and argentaffin negative. An extensive battery of immunohistochemical stains was negative for specific peptide products and keratin. Electron microscopy disclosed numerous cytoplasmic membrane-bound electron-dense core secretory granules and masses of intermediate microfilaments. A review of the pertinent medical literature revealed 5 previously reported cases.

Topics: Adult; Carcinoid Tumor; Cytoplasmic Granules; Cytoskeleton; Humans; Keratins; Kidney Neoplasms; Male; Microscopy, Electron; Staining and Labeling