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Diagnosis of metastatic pleomorphic giant cell carcinoma of the pancreas using fine catheter aspiration cytology.

The value of fine catheter aspiration cytology in the diagnosis of metastatic tumours is illustrated by a case of pleomorphic giant cell carcinoma of the pancreas which had metastasized to the peritoneal cavity. The finding of unequivocal malignant cells obviated the need for further diagnostic procedures. Electron microscopy and immunostaining further substantiated the light microscopic cytodiagnosis and identified the tumour type and source of the primary tumour. Furthermore, subsequent cell block preparation from the aspirated material demonstrated the histological features of this tumour.

Aged↗

[Immunohistochemical study of monomorphic adenoma (clear cell and basal cell) and pleomorphic adenoma of the parotid gland].

The present paper reports the results of an immunohistochemical study of 6 cases of monomorphic (2 clear cell, 4 basal cell) and 12 cases of pleomorphic adenomas in the parotid gland. The surgical specimens, embedded in paraffin, were tested by antisera vs. epithelial cell markers with epithelial membrane antigen (EMA) and cytokeratins (CK). They were also tested vs. myoepithelial and non-epithelial markers with S-100 protein and Glial Fibrillary Acidic Protein (GFAP). In pleomorphic adenomas, positive cells were found for all the tested antigens. Positive cell distribution showed a marked variability from case to case and even within each area, depending on cell morphology. In particular, areas showing tubular structures were constantly EMA-positive and CK-positive in more than 50% of the cases. In epithelioid areas EMA was negative while many cells were variably positive for CK, S-100 and GFAP. At times, the same cell proved positive to two different antigens. In those fuso-stellate (myxoid) cell areas considered to be of myoepithelial origin, cells were slightly CK-positive and widely GFAP and S-100 positive. In basal cell adenomas, widespread CK positivity was uniformly present while rare, focal positivity was evidenced for EMA and widespread non reactivity was found for S-100 and GFAP. In clear cell adenomas focal CK expression was found in the tubular lumina while clear cells, of myoepithelial origin, were steadily S-100 positive and GFAP-negative. It was noted that a sort of S-100/GFAP positive myoepithelial cell with fuso-stellate morphology was present in pleomorphic adenomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

Pleomorphic large cell hemato-lymphoma (the so-called "malignant histiocytosis"): clinicopathological and immunophenotypic studies in 35 cases.

Thirty-five patients diagnosed with "malignant histiocytosis" from 1984 to 1989 were studied for clinical, laboratory, histopathological features as well as survival and response to therapy, Immunocytochemistry and immunophenotypic studies were performed in 12 cases using the paraffin immunoperoxidase method. The staining included alpha-1 antichymotrypsin, muramidase, immunoglobulins and monoclonal antibodies specific for T, B lymphocytes and macrophage. From the clinical features, responsiveness to therapy and survival, the patients were divided into 2 groups: the non-responders (25 cases) and responders (10 cases) groups. Very short median survival of 1.25 months was found in the non-responders, whereas, longer median survival of 14.15 months was found in the responder group. Important different clinical and laboratory features were observed among these two groups. Unresponsiveness to treatment; rapidly progressive pancytopenia, increased hemophagocytosis, presentation of immature cells in blood with extensive infiltration of malignant cells in the bone marrow; severe jaundice and deterioration of hepatic function accompanied by early extranodal involvement were almost exclusively observed initially in the non-responder group. Satisfactory response to treatment was observed only in the responder group. Similarity of histopathology, cytology and immunophenotype was observed in these two groups. The immunophenotypic study in 12 cases showed 5 cases of B-cell lymphoma, 3 cases of T-cell (with 1 Ki-1 -positive) lymphoma; 1 case of Ki-1 positive non-T, non-B anaplastic large cell lymphoma; and 3 cases of undetermined cell lineage. From this study, so-called "malignant histiocytosis" appears to be a disorder of heterogeneity. The immunophenotypes of malignant cells indicated that their origin belonged mostly to lymphoid cell lineage. Based on their clinical feature of the early hematogenous spread along with the distinct histopathological and immunophenotypic findings, the term "pleomorphic large cell hematolymphoma" is proposed to be used instead of the old misnomer, "malignant histiocytosis" (MH).

Adolescent↗

KRAS oncogene mutations suggest a common histogenetic origin for pleomorphic giant cell tumor of the pancreas, osteoclastoma of the pancreas, and pancreatic duct adenocarcinoma.

Giant cell neoplasms of the pancreas are rare tumors of uncertain histogenesis. Mutation of the KRAS oncogene is common in typical pancreatic duct adenocarcinoma. We have analyzed DNA from five pancreatic tumors with giant cells for mutations in the KRAS oncogene and found alterations of the second position of codon 12 in each case (four G > A transitions and one G > C transversion). The common mutation pattern in tumors with giant cells and duct adenocarcinoma suggests a common route to malignant transformation and may indicate a shared histogenesis. We also tested 11 cases of malignant fibrous histiocytoma, a histological mimic of pleomorphic giant cell tumor, for mutations in the KRAS oncogene. The absence of KAS mutations in each of the malignant fibrous histiocytomas (MFHs) and in other histologically similar tumors may provide assistance in the differential diagnosis of pleomorphic pancreatic tumors.

Adenocarcinoma↗

Canine hepatocellular carcinoma.

In a study of 110 primary hepatic neoplasms in dogs, 55 hepatocellular carcinomas and two combined hepatocellular and cholangiocarcinomas were diagnosed. These neoplasms were classified into the following 11 groups based on histo-architectural pattern: trabecular, peliod, cobblestone, peritheliomatous, anaplastic, pseudoglandular, pleomorphic, scirrhous, clear cell, solid, and combined hepatocellular and cholangiocarcinoma. The neoplastic hepatocytes varied from almost normal to highly anaplastic spindle cells. Pleomorphic and giant cells were common in some groups, rare or absent in others. Metastasis was found in 61% (35 of 57), in contrast to a much higher percent in man, indicating the possibility of a different pathogenesis in the dog.

Adenoma, Bile Duct↗

Histologic malignancy grading of invasive ductal breast carcinoma. A regression analysis of prognostic factors in low-risk carcinomas from a multicenter trial.

In a prospective adjuvant trial including patients with primary operable breast cancer, invasive carcinomas of ductal type were subjected to histological malignancy grading. The parameters investigated were tubule formation, number of mitoses and cell pleomorphism. A Cox regression model for survival data was applied to evaluate the impact of the histological parameters on prognosis in 1809 patients with low-risk carcinomas. Cell pleomorphism proved superior to the other histologic tumor characteristics. It was found that low-risk invasive ductal carcinomas with severe cell pleomorphism had an excess recurrence intensity of 209% relative to carcinomas with no pleomorphism. It is therefore suggested that polymorphous invasive ductal breast carcinomas, other things being equal, should be regarded as high-risk tumors in future clinical trials. Finally it was found that the tripartite malignancy grading 1, 2 and 3 characterizing each of the histological parameters was not equidistant. Consequently, the traditional tripartite histologic scoring needs reconsideration.

Adult↗

The ultrastructural aspects of neoplastic myoepithelial cell in pleomorphic adenomas of salivary glands.

The purpose of this study has been to establish the major ultrastructural aspects of the myoepithelial cell and the myoepithelial-like cells proliferated in the pleomorphic adenomas of salivary glands. Thus, twelve benign pleomorphic adenomas of salivary glands have been studied by electron-microscopy transmission techniques. Our analysis has proved the proliferation of two major cellular populations, one of ductal type and one of myoepithelial type, which tried to reproduce the tubulo-acinar cytoarchitecture from the normal salivary glands. We have also noticed the key role of the so-called 'modified' myoepithelial cells from the periphery of the proliferating epithelial units in the genesis of the myxoid and chondromyxoid tumoral stromal areas. All these ultrastructural aspects have explained the great histological diversity of these salivary gland neoplasms as well as the key role of the myoepithelial cell in its histogenesis.

Adenoma, Pleomorphic↗

Pigmented astrocytoma with suprasellar location: case report and literature review.

A large suprasellar, partly cystic, contrast-enhancing tumor was resected from a 19-year-old woman who presented with bitemporal visual field defects and reduced visual acuity. Grossly, the tumor was brown and located in the subarachnoid space. Histologically, it was composed of spindle and pleomorphic cells, including giant tumor cells, with markedly pleomorphic nuclei. Reticulin fibers surrounded single cells and small groups of cells. Very few mitotic figures were found in the tumor, and no necrosis or microvascular proliferation was seen. The tumor thereby resembled a pleomorphic xanthoastrocytoma. Many of the tumor cells contained a dark-brown intracytoplasmic pigment, shown to be melanosomal melanin by ultrastructural examination. Immunohistochemical examination demonstrated that the pigment was present in glial tumor cells. Only four cases of pigmented astrocytic tumors have been published, none of these were suprasellar. Our patient received fractionated radiotherapy with a total dose of 48.6 Gy 14 months after gross total removal of the tumor. She is alive without relapse after 12-year follow-up.

Adolescent↗

Pleomorphic B cell neoplasm with monoclonal IgA secretion: a case report.

A case of non-myelomatous malignant disease with IgA paraproteinemia is described. A pleomorphic lymphoid/plasmacytoid infiltrate was found in the bone marrow. While the cells studied had some ultrastructural characteristics closer to myelomatosis than Waldenström's macroglobulinemia, immunofluorescence showed IgA in both the cytoplasm and at the cell surface, as seen with IgM in macroglobulinemia but not with IgA in typical IgA myelomatosis. This case illustrates that IgA paraproteinemia may be produced in association with pleomorphic B cell proliferative diseases as well as myelomatosis. There is probably a spectrum of disease states as with IgM paraproteinemia.

Adult↗

Molecular evidence that the stromal and epithelial cells in pleomorphic adenomas of salivary gland arise from the same origin: clonal analysis using human androgen receptor gene (HUMARA) assay.

Salivary gland pleomorphic adenomas are characterized by a biphasic growth of "epithelial" and "stromal" regions. The "epithelial" region is a compactly organized mixture of both luminal and nonluminal cells, whereas the stromal region is composed predominantly of the nonluminal cells. Using the polymerase chain reaction (PCR)-based HUMARA assay on DNA from formalin-fixed, paraffin-embedded tissues from pleomorphic adnomas of female patients, we intend to clarify the clonal relation between the luminal and nonluminal cells and the clonal nature of the morphologically diverse nonluminal cells in this tumor. HUMARA, the human androgen receptor gene, is located on the X chromosome and contains a segment of polymorphic CAG tandem repeats in exon 1. Several methylation-sensitive HhaI restriction sites are located 5' to these CAG repeats. It is an ideal tool to study clonality of female tissues by examining the methylation pattern. Of the 13 cases analyzed, 3 were homozygous at the HUMARA locus and therefore noninformative. The remaining 10 cases were informative. All 10 cases showed a monoclonal pattern in the stromal area, indicating that the morphologically diverse nonluminal cells are monoclonal. Eight of the 10 cases showed monoclonality in the "epithelial" areas, suggesting a common clonality between luminal and nonluminal cells. Of the remaining 2 samples, 1 was polyclonal for the "epithelial" region, and the other was not amplifiable. Our data provide the first molecular evidence that the luminal and nonluminal cells in pleomorphic adenomas arise from the same clone in most cases, and the morphologically diverse nonluminal cells are monoclonal.

Adenoma, Pleomorphic↗

[Molecular analysis in 23 patients with T-lymphomas].

Gene rearrangement analysis has been performed in 23 patients with T-cell lymphoproliferative diseases: 4 cases with T-gamma lymphocytosis, one case of a Sezary's syndrome, one case of T-cell angioimmunoblastic lymphoma, two cases of T-cell lymphoepitheloid lymphoma, 11 patients with T-cell pleomorphic lymphoma, 3 cases of large anaplastic T-cell lymphoma and one case of T-cell lymphoblastic lymphoma. Rearranged banding patterns have been observed for at least one of the T-cell receptors (TCR) in 19 of the cases, and germ line configuration of the TCR and Ig genes in the other four. Likewise, both Ig and TCR rearrangements have been observed in three cases (one case of T-cell pleomorphic lymphoma, one case of large anaplastic T-cell lymphoma and one case of T-cell lymphoblastic lymphoma). Molecular genetic techniques have been used in order to direct monoclonal proliferations of T cell in the tumoral tissues, to determine the T- or B-cell lineage of the neoplasia and also to outline the molecular characteristics of each group that constitutes the complex classification of T-cell malignancies.

Gene Rearrangement, B-Lymphocyte↗

Pleomorphism and acetylene-reducing activity of free-living rhizobia.

Cowpea-type Rhizobium sp. strain 32H1 and Rhizobium japonicum USDA 26 and 110 grown on a glutamate-mannitol-gluconate agar medium showed increases in the number of pleomorphic cells coincident with their acetylene-reducing activity. Pleomorphs appeared to be inhibited in growth nonuniformly, because acetylene-reducing cultures were mixtures of rod, branched (V, Y, and T), and other irregularly shaped cells. In contrast, strain USDA 10 consistently failed to reduce acetylene, even though it also could grow and yield pleomorphic cells under various conditions. With minimal inhibitory supplements (5 micrograms per ml of medium) of nalidixic acid and novobiocin as cell division inhibitors, an increase in pleomorphic cells was observed, but the inhibited cultures displayed lower acetylene-reducing activity. A study of pleomorphic cells derived in different ways indicated that not all pleomorphs reduce acetylene.

Acetylene↗

Adenosquamous carcinoma of the pancreas with an acantholytic pattern together with osteoclast-like and pleomorphic giant cells.

A 45 year old man presented with abdominal pain, loss of appetite, and significant weight loss over a period of about four weeks. Imaging of the abdomen showed a mass in the region of the head of the pancreas. In view of the size of the mass and the clinical picture, a Whipple's procedure was performed. Histological evaluation of the pancreatic tumour showed an adenosquamous carcinoma (predominantly composed of squamous carcinoma), which was extensively infiltrative with perineural invasion and involvement of peripancreatic lymph nodes. Areas of pancreatic intraepithelial neoplasia grade III and merging of the squamous and adenocarcinoma components were evident. Unusual histological features that characterised this case included a pronounced acantholytic pattern within the squamous carcinoma component, and the presence of both osteoclastic and pleomorphic giant cells. Giant cells have not been documented previously in association with an adenosquamous carcinoma. Although an acantholytic pattern has been noted in squamous carcinomas in other sites, this is the first report of such a pattern in an adenosquamous carcinoma of the pancreas.

Acantholysis↗

Primary invasive signet-ring cell melanoma.

The histopathological variants of malignant melanoma include the common type (lentigo maligna, superficial spreading melanoma, nodular melanoma, acrolentiginous melanoma), spindle cell, desmoplastic, balloon cell, pleomorphic (fibrohistiocytic), myxoid, small cell melanoma and malignant blue nevus. Recently, signet-ring cell melanoma was introduced as an additional cytologic variant. We describe a 72-year-old patient with a primary signet-ring cell melanoma of the skin located on the upper arm. Histopathologic examination disclosed a melanocytic tumor extending from the epidermis to the deep reticular dermis. Numerous pleomorphic tumor cells showed large, intracellular vacuoles and oval to spindle-shaped nuclei at their periphery. Mitotic figures and multinucleated melanocytes were also observed. Some of the signet-ring cells exhibited cytoplasmatic periodic acid-Schiff (PAS)-positivity. Immunohistochemistry showed positive reaction of the tumor cells for S-100, HMB-45 protein and vimentin, confirming their melanocytic differentiation. Tumor cells were negative for cytokeratins, epithelial membrane antigen (EMA), and carcinoembryonic antigen (CEA). The signet-ring cell melanoma disclosed an invasion to Clark Level IV and tumor thickness of 2.2 mm. Signet-ring cell melanoma is a rare morphologic variant of melanoma. Its recognition is important for differentiation from other tumors featuring signet ring cells.

Aged↗

CD30 expression in follicular lymphoma.

CONTEXT: CD30(+) anaplastic large cell lymphomas were originally described as being of T-cell, null cell, and B-cell origin. CD30, however, is not a specific marker of anaplastic large cell lymphoma and has been found to be expressed in reactive as well as neoplastic populations as a probable activation marker. In addition, CD30(+) cells have also been described in both diffuse large B-cell and follicular lymphomas (FLs), resembling the pattern seen in reactive tonsils and lymph nodes. OBJECTIVE: We report an index case of FL with CD30 expression, which on initial touch preparations and flow cytometric immunophenotyping revealed a prominent population of CD30(+) cells with marked cellular pleomorphism (anaplasia) in a background of typical FL. Immunohistochemistry of the paraffin section for CD30 in our index case confirmed unequivocal CD30(+) pleomorphic cells in the malignant nodules in occasional clusters. This case prompted a study of additional cases of FL for pattern of immunoreactivity with CD30 on paraffin sections. DESIGN: Twenty-two additional cases of FL (grades 1-3) were retrieved for CD30 immunoperoxidase staining as in the index case. RESULTS: This study demonstrated 32% of the additional cases of FL had definitive CD30(+), large, pleomorphic malignant cells by paraffin immunohistochemistry. In 2 cases (9%), the pattern of immunoreactivity with CD30 showed clustering and variable staining of large cells, as our index case. CONCLUSION: This study underscores the morphologic and immunophenotypic spectrum of FL that includes CD30 staining and cellular pleomorphism.

Aged↗

Pleomorphic (spindle/giant cell) carcinoma of the lung. A clinicopathologic correlation of 78 cases.

BACKGROUND: The authors undertook this study to define the clinical and histologic characteristics of spindle and giant cell carcinomas of the lung and the survival and prognostic features of these tumors. METHODS: Seventy-eight cases of pleomorphic (spindle and/or giant cell) carcinoma of the lung were studied by light microscopy and immunohistochemistry to establish clinical, gross, and histologic parameters. Follow-up information was obtained from contributing physicians and analyzed by statistical means to determine prognostically significant parameters. RESULTS: The patient population consisted of 57 men and 21 women (male to female ratio, 2.7 to 1) between the ages of 35 and 83 years (mean, 62 years). Clinically, 58 patients (80%) presented with symptoms including thoracic pain, cough, and hemoptysis, whereas 14 (18%) were asymptomatic. At the time of diagnosis, 41% of the patients had clinical Stage I lesions, 6% Stage II lesions, 39% Stage III lesions, and 12% Stage IV lesions. Histologically, foci of squamous cell carcinoma were present in 8% of the tumors, large cell carcinoma in 25%, and adenocarcinoma in 45%. The remaining 22% of neoplasms were completely spindle and/or giant cell carcinomas. Spindle and giant cell carcinomas were found together in 38% of the patients. In the 69 patients for whom follow-up information was obtained, 53 (77%) died within 7 days to 6 years after diagnosis, with a 23-month mean survival (median, 10 months) (Kaplan-Meier method). There was a significant shortening of survival for patients with tumor size greater than 5 cm, clinical stage greater than 1, and lymph node involvement. The presence of nodal metastases was the most significant single prognostic factor, whereas the presence of squamous or adenocarcinomatous differentiation did not have an impact on length of survival. CONCLUSIONS: The frequency with which spindle and giant cell carcinomas are found together, their frequent association with other histologic subtypes of lung carcinoma, and the similar clinicopathologic features of these tumors suggest that they are best regarded as one type of lung cancer called pleomorphic carcinoma.

Adenocarcinoma↗

Cytologic features of granulosa cell tumors in fluids and fine needle aspiration specimens.

OBJECTIVE: To describe the cytologic features of granulosa cell tumors in fluids and fine needle aspiration specimens, with histologic confirmation. STUDY DESIGN: Histologically confirmed granulosa cell tumors, 6 adult type and 1 juvenile type, were identified. All patients had local recurrences or metastases. Eleven specimens from 7 patients, including cytologic samples, cell blocks and histology, were reviewed. Inhibin immunostaining was performed on cell blocks to aid identification of this group of tumors in the cytologic and histologic samples. RESULTS: The patients were 22-72 years old. Sites included ovary and peritoneum; there were pelvic recurrences and metastatic lesions in the spleen, liver, perirectum and cervical lymph node. Cytologic features of adult granulosa cell tumors included 3-dimensional clusters, resettes loose monolayers and individual cells. Other features were Call-Exner bodies, vacuolated cytoplasm, exuberant capillaries associated with papillarylike fronds, a second population of elongated theca cells, and prominent or rare nuclear grooves. In juvenile granulosa cell tumor the features observed were monolayers, loosely cohesive sheets, single cells, occasional larger pleomorphic cells with nuclear clefting and nuclear protrusions, vacuolated cytoplasm, finely granular chromatin and frequent mitoses. The overall cytologic and histologic correlation was good. Inhibin was focally positive in one peritoneal fluid, correlating with the focal pattern of staining seen on histology. CONCLUSION: A definitive cytologic diagnosis of granulosa cell tumor can be made based on the above criteria. Aggressive tumors are discohesive and show pleomorphism and nuclear protrusions. Inhibin stain may be helpful in identifying granulosa cell tumors in cell block specimens.

Adult↗

[An autopsy case of primary malignant melanoma of the esophagus--appraisal of radiation therapy].

A rare case of primary malignant melanoma of the esophagus is reported. Our case is of interest because an extraordinary effect was observed early during conventional radiation therapy. The primary lesion was irradiated with 60 Gy, it almost disappeared. Metastatic lesions were irradiated with 30 Gy, their volume decreased by more than 50%. At autopsy, these lesions were more or less unchanged. Histologically, cells from the main tumor were small and round. The growth of pleomorphic cells with large amounts of melanin granules was observed in the regions of irradiation. These findings suggest that the small round cells in malignant melanoma are radiosensitive and the pleomorphic cells with abundant melanin granules are radioresistant.

Aged↗