Well differentiated and small cell neuroendocrine carcinomas of the lung. Two related but distinct clinicopathologic entities

Twenty-two resected pulmonary well differentiated neuroendocrine carcinomas (WDNC) were re-evaluated histologically as were 28 resected intermediate-small cell neuroendocrine carcinomas (IC-SCNC). WDNC were distinguishable from IC-SCNC by their consistently recognizable organoid architecture, and by the absence or limited extent of necrosis. Furthermore, WDNC could be subclassified into 3 subsets based upon the degrees of pleomorphism, local and vascular invasion, and stromal fibrosis, the mitotic count, and the extent of tumor necrosis. Whereas all those parameters were important in discriminating between WDNC and IC-SCNC, the quality of the organoid architecture, and the extent and pattern of necrosis emerged as the most significant. WDNC with the more aggressive histologic features (subset III) had, as a group, a distinctly worse clinical course that those displaying blander features (subsets I and II). Nevertheless, even subset III of WDNC had, as a group, a longer survival than similarly treated Stages I and II IC-SCNC. We conclude that the histologic spectrum of WDNC is broader than generally recognized. Moreover, 3 subsets of WDNC are definable based on conventional histologic criteria provided sufficient, well preserved samples are examined. Even the most aggressive subset of WDNC can be thus histologically discriminated from IC-SCNC, and, given comparable stages, has a better prognosis than the latter.     

Intraductal papillary neoplasms of bile duct. A distinct entity like its counterpart in pancreas

To recognize the new entity-intraductal papillary neoplasia of bile duct in liver, the authors reviewed the clinical records of sixteen patients, analyzed the microscopic features, and selected immunohistochemical reactivity (cytokeratins and mucins) that might correlate with classification. Ten patients were male and six were female, with a mean age of 58 years (range, 21-73 years). According to their cell phenotypes, these papillary tumors were classified as intestinal type (6 cases), pancratobiliary type (4 cases), gastric type (5 cases) and oncocytic type (1 case). Most were located in the left hepatic duct and accompanied with bile duct dilatation (10 cases). Eight showed minimal expansile invasion into the ductal wall and eight were noninvasive. Five patients were treated with a hepatectomy, three underwent segmental resections, and one underwent a left hepatic lobectomy. One patient died of unrelated causes 6 years after operation, and another died of postoperative complications. The remaining 7 patients are alive and disease free 1-5 years after surgery. Because of its distinct clinical, pathological features and a favorable prognosis can be expected after complete surgical resection, we suggested that intraductal papillary neoplasia should be distinguished from other types of peripheral cholangiocarcinoma, as a distinct entity, like its counterparts in the pancreas. Neoexpressed and overexpressed mucins are of clinical value as a marker for supportive diagnosis, prognosis or monitoring therapy.     

Cytopathologic and clinicopathologic features of ovarian hepatoid carcinoma. A case report

BACKGROUND: Hepatoid carcinoma is a rare ovarian tumor and is thought to be a different histopathologic subtype from hepatoid-type yolk sac tumor based upon its pathologic features. However, the cytopathologic characteristics of ovarian hepatoid carcinoma (OHC) have not been reported previously. We report the clinicopathologic and cytopathologic features and immunoreactivity of a case of OHC. CASE: A 36-year-old woman presented to our department with lower abdominal pain. A left ovarian tumor was found on pelvic examination, magnetic resonance imaging and computed tomography. The tumor was diagnosed as a hepatoid carcinoma of the left ovary based upon the histopathology of the surgically resected specimen. Cytopathologic specimens from a tumor touch preparation of the tumor exhibited pleomorphic tumor cells with abundant cytoplasm. The nuclei contained rough, granular chromatin and large, prominent nucleoli. Several tumor cells were multinucleated. Tumor cells were immunoreactive for alpha-fetoprotein (AFP). Hematoxylin and eosin staining revealed that the tumor cells were in a sinusoidal pattern resembling hepatocellular carcinoma without any glandular formation. The tumor cells were negative for human chorionic gonadotropin while positive for AFP, alpha-1-antitripsin, CA-125 and carcinoembryonic antigen. CONCLUSION: Cytopathologic examination is of considerable aid in the diagnosis of OHC since cytopathologic preparations highlight the characteristic cell pleomorphism.     

Fine needle aspiration cytodiagnosis of nasopharyngeal carcinoma in cervical lymph nodes. A study of 40 cases

The cytologic features of fine needle aspiration (FNA) samples of 40 metastatic nasopharyngeal carcinomas in cervical lymph nodes were reviewed. FNA was performed with 21-gauge or 23-gauge needles; the FNA smears were stained with the Papanicolaou stain or with hematoxylin and eosin. Several typical cytologic features were noted. All cases showed the presence of clusters of cohesive tumor cells, most of which were undifferentiated. Medium-sized oval vesicular nuclei were present in 85% of the cases; all cases had prominent nucleoli. The cytoplasm was generally pale, with ill-defined boundaries in 87.5% of the cases. Mitoses were present in 75% of the cases. Mature lymphocytes were intermingled with tumor cells in all cases. The cytologic features correlated with the histologic features in surgical biopsies of the nasopharynx and lymph nodes. The results show that FNA of cervical lymph nodes can aid in the diagnosis of otherwise occult nasopharyngeal carcinoma and in detecting residual or recurrent nodal disease in patients with nasopharyngeal carcinoma who had undergone treatment.     

Endocyte endometrial smears in the cytodiagnosis of endometrial carcinoma

The cytologic diagnosis of endometrial cancer using material obtained with the Endocyte endometrial sampler was assessed for 874 patients. The samples obtained were smeared directly on slides for fixation and staining; the smears were more difficult to assess than cervicovaginal smears, however, due to the presence of blood, the small size and density of the cells and the flattened three-dimensional architecture of the tissue fragments obtained. Only 8.2% of the samples were classified as inadequate; repeat sampling in some of those cases produced diagnostic material. All 12 cases of carcinoma (including one case in a woman less than 40 years of age) were diagnosed by cytology as malignant; however, the original cytologic sample in one of those cases was inadequate. For the diagnosis of benign versus malignant, cytology had a sensitivity of 92%, a specificity of 100% and predictive value of 100%. Cytology also diagnosed as suspicious the smears from 5 of 13 cases of endometrial hyperplasia and 2 of the 9 cases of endometrial polyps. The cytologic findings for benign and malignant samples are described and illustrated in detail. Relative to other endometrial sampling devices, the Endocyte is inexpensive and was easily used by the gynecologist and well tolerated by the patients, with no complications and minimal discomfort.     

Sputum cytodiagnosis of disseminated histiocytic lymphoma. A case report

Cytohistologic evidence of pulmonary involvement with histiocytic lymphoma was discovered in a patient nine years after the original clinical diagnosis was made. The positive sputum cytologic diagnosis confirmed the radiologic impression of pulmonary involvement, which was substantiated by an open lung biopsy. This case report demonstrates the value of periodic sputum cytology in the diagnosis and management of histiocytic lymphoma. Sputum cytology should be utilized more frequently in the monitoring of pulmonary histiocytic lymphoma.     

Fine needle aspiration cytodiagnosis of secretory carcinoma of the breast

Secretory carcinoma (SC) of the breast is a rare variant of breast malignancy and its cytological features in fine needle aspirates have only recently been described. In this communication, our experience with four cases of SC of the breast is presented in which the diagnosis was established on fine needle aspiration cytology (FNAC). In all cases, the samples were cellular and featured diffuse, prominent, intracytoplasmic vacuoles and secretion in malignant cells and occasional signet-ring like forms. The cytodiagnosis of SC in all the cases correlated with subsequent examination of cell blocks of the aspirate and tissue. Cytochemical stains showed diffuse positivity for mucin by alcian blue stain in the vacuolated cells which was periodic acid-Schiff positive and resistant to diastase digestion. Oil-red O staining was negative. Immunopositivity to carcinoembryonic antigen, cytokeratin (CAM 5.2), B72.3 and epithelial membrane antigen was found in malignant cells. The cytodiagnostic criteria for SC of the breast, characteristic cytological features which are useful in a correct FNAC diagnosis and differentiation from other pertinent breast carcinomas, are discussed.     

Evidence of acid phosphatase in the cytoplasm as a distinct entity

A study of subcellular acid phosphatase distribution in mammalian tissues shows that isozymes with specific functions are compartmentalized in the cells. The enzyme may be generalized into two types: type A and type B. They are shown by several means to be distinct entities. Type A is confined to the cytoplasm and is inhibited by Cu2+, HCHO, and the coupling agents (for enzyme staining) fast blue RR salt and fast Garnet GBC salt (newly discovered inhibitors), but is insensitive to fluoride and L-(+)-tartrate. Type B is localized in the organelles, presumably lysosomes, in both soluble form and membrane-bound form, with inhibitor sensitivity exactly opposite to that of type A enzyme. Types A and B consist of different sets of isozymes, with sensitivities to inhibitors resembling those observed with the crude extracts of subcellular fractions. Acid phosphatase that exhibits a phosphoryl transfer property was identified as type A enzyme. Type A enzyme has a slightly higher optimal pH and is inhibited by alloxan, whereas for type B, the addition of alloxan broadens the optimal pH to a higher range and elevates the activity of pH 7.4 from negligible to about 30-40% of that obtained under optimal conditions. The alloxan-mediated elevation of type B enzyme activity to this level at the physiological pH may be of considerable significance. Type B enzyme has a high affinity for metabolic intermediates and nucleotides, while type A has an extremely low affinity for these substrates. Cytoplasmic acid phosphatase (type A) is a significant enzyme population and its activity is not related to the lysosome density in the cells. Type A enzyme in the cytoplasm is thus shown to be an entity distinctly different from type B enzyme in the lysosomes. These findings suggest that the physiological functions of type A acid phosphatase, such as metabolic regulatory processes, merit further studies because of the phosphoryl transfer activity and cytoplasmic localization of the enzyme.     

Cytology of metastatic neuroendocrine (Merkel-cell) carcinoma in pleural fluid. A case report

A case of Merkel-cell (neuroendocrine) carcinoma of the skin with extensive metastases, including pleural effusion, occurring over 20 years after primary resection and treatment, is reported. The histologic appearance of the primary neoplasm was identical to that seen in the biopsy specimens of the metastatic carcinoma involving the great toe and inguinal lymph nodes and to that of the residual neoplasm tissue found at necropsy. Electron microscopic examination of a lymph node metastasis demonstrated cytoplasmic microfilaments and numerous dense-core, peripheral, neurosecretory granules, as previously described in Merkel-cell carcinoma. Cytologic examination of a pleural fluid specimen demonstrated numerous small malignant cells closely resembling the cells seen in the histopathologic sections from the surgical and necropsy tissues involved by metastatic carcinoma. This is the first report of the cytologic findings in a patient with Merkel-cell carcinoma metastatic to the pleural cavity.     

Fine needle aspiration cytodiagnosis of subcutaneous sacrococcygeal myxopapillary ependymoma. A case report.

A tumor located subcutaneously over the coccyx of a 32-year-old woman was diagnosed by fine needle aspiration (FNA) cytology as a myxopapillary ependymoma originating in the soft tissue. The FNA smears showed characteristic papillary structures, consisting of a central mucinous core surrounded by cuboidal-to-columnar cells, and scattered ependymal cells. The excised tumor was connected to neither the filum terminale nor the cauda equina. Histopathologic study confirmed the cytologic findings.     

Dendritic cell immunotherapy induces antitumour response in parathyroid carcinoma and neuroendocrine pancreas carcinoma.

Parathyroid carcinomas and neuroendocrine carcinomas of the pancreas are rare malignancies in humans. Because of their low radio- and chemosensibility, they fail to respond to conventional therapy. We therefore tested a dendritic cell immunotherapy in an attempt to control the tumour growth in two patients. Studies on mice and humans have demonstrated the potent capacity of dendritic cells to induce specific antitumour immunity. Mature dendritic cells were generated from peripheral blood monocytes in the presence of granulocyte/macrophage colony-stimulating factor, interleukin 4 and tumour necrosis factor alpha. Dendritic cells were either loaded with parathyroid hormone (PTH) or with (pancreas) tumour-derived lysate (TL), respectively, and were delivered by subcutaneous injections. All immunizations were well tolerated with no side effects, and were administered on an outpatient basis. After repeated vaccinations, specific in vivo immune response was demonstrated by positive delayed-type hypersensitivity (DTH) toward PTH or TL, demonstrating the efficient generation of antigen-specific memory T-cells. DTH reactivity was accompanied by a significant decrease of tumour markers in both patients. This approach might be generally applicable to other advanced, radio- and chemotherapy-resistant endocrine malignancies.     

Fine needle aspiration biopsy of neuroendocrine breast carcinoma metastatic to the thyroid. A case report

BACKGROUND: Tumors showing neuroendocrine differentiation arise in a wide range of organs, and metastatic neuroendocrine tumors may be difficult to differentiate from primary tumors. This report describes an unusual case of metastatic breast carcinoma with neuroendocrine differentiation that presented as a solitary thyroid nodule. The diagnosis was made by fine needle aspiration biopsy (FNAB). CASE: A 52-year-old woman presented with a thyroid nodule and bilateral enlarged supraclavicular fossa lymph nodes. FNAB revealed a neuroendocrine carcinoma. Further questioning revealed that the patient had had a breast carcinoma resected eight years previously. The diagnosis of metastatic neuroendocrine breast carcinoma was established by immunocytochemistry. The patient received antiestrogen therapy but subsequently developed skeletal metastases. CONCLUSION: Neuroendocrine carcinomas from various sites show similar cytologic features. In this case, a diagnosis of breast carcinoma metastatic to the thyroid was suggested by the clinical history and confirmed by FNAB with immunocytochemistry.     

Three distinct modes of exocytosis revealed by amperometry in neuroendocrine cells

Neurotransmission requires Ca²⁺-dependent release of secretory products through fusion pores that open and reclose (partial membrane distention) or open irreversibly (complete membrane distention). It has been challenging to distinguish between these release modes; however, in the work presented here, we were able to deduce different modes of depolarization-evoked exocytosis in neuroendocrine chromaffin and PC12 cells solely by analyzing amperometric recordings. After we determined the quantal size (Q), event half-width (t₅₀), event amplitude (I_peak), and event decay time constant (τ_decay), we fitted scatter plots of log-transformed data with a mixture of one- and two-dimensional Gaussian distributions. Our analysis revealed three distinct and differently shaped clusters of secretory events, likely corresponding to different modes of exocytosis. Complete membrane distention, through fusion pores of widely varying conductances, accounted for 70% of the total amount of released catecholamine. Two different kinds of partial membrane distention (kiss-and-run and kiss-and-stay exocytosis), characterized by mode-specific fusion pores with unitary conductances, accounted for 20% and 10%, respectively. These results show that our novel one- and two-dimensional analysis of amperometric data reveals new release properties and enables one to distinguish at least three different modes of exocytosis solely by analyzing amperometric recordings.     

Fine needle aspiration cytodiagnosis of leiomyosarcoma of the breast. A case report

BACKGROUND: Leiomyosarcoma of the breast is a rare tumor. Here we present a case in an elderly female in which the diagnosis was suggested from an aspirate sample. CASE: An 80-year-old female presented with an irregular, firm mass in the left breast of a few months' duration. In view of the clinical suspicion of a tumor, fine needle aspiration was performed. It showed a large number of dissociated cells and compact sheets of spindly and round cells with pleomorphic, hyperchromatic and anaplastic nuclei; mitoses; nucleoli; and somewhat-vacuolated, eosinophilic cytoplasm. Examination of the cell block, tumor tissue and immunostaining further suggested the cytologic impression of a leiomyosarcoma. CONCLUSION: Although leiomyosarcoma of the breast is very rare, fine needle aspiration cytology may allow the diagnosis to be suggested. Correlation with cell block findings and the application of appropriate immunostains as an adjuvant to standard cytologic and histologic stains may allow a more confident diagnosis.