Carcinoid tumors of the lung: cytologic differential diagnosis in fine-needle aspirates

Pulmonary carcinoid tumors presenting as peripheral or coin lesions are rare and radiologically may resemble other primary or metastatic neoplasms in the lung. This study consisted of the cytologic evaluation of fine-needle aspirates from five peripheral carcinoid tumors of the lung with particular reference to the differences between the cytologic manifestations of this neoplasm and of small-cell carcinoma and well-differentiated adenocarcinoma. Aspirates of typical carcinoid tumors are characterized by isolated cells and loose aggregates of cells; spindle- and oval-shaped cells of uniform size with scanty, pale eosinophilic cytoplasm; and nuclei with evenly dispersed finely granular chromatin and usually prominent single micronucleoli with occasional macronucleoli. In contrast, the cells of small-cell carcinoma are pleomorphic and arranged in noncohesive loose aggregates, their cytoplasm is scanty, and they show nuclear molding. Their nuclei are hyperchromatic with fine to coarsely granular chromatin. The cells of well-differentiated adenocarcinoma are arranged in three-dimensional clusters or loose aggregates of relatively uniform cells with a columnar configuration. The nuclei are uniformly round and hyperchromatic with finely granular chromatin. Macronucleoli are usually prominent. This study demonstrates that cytologic analysis of fine-needle aspirates can play a significant role in the evaluation and management of peripheral lung tumors.     

Hyperplastic and neoplastic endocrine cells of the pancreas in aspiration biopsy

Aspiration biopsy of four primary endocrine tumors of the pancreas showed single and large sheets of tumor cells. Tumor cells were polygonal in shape with ill-defined, filmy or granular cytoplasm and regular round nuclei containing a finely granular chromatin pattern and inconspicuous or prominent nucleoli. Focal gland-like arrangement was seen in several sheets of tumor cells. Aspirate from liver metastases of an endocrine tumor of the pancreas showed single and clustered oval cells with granular cytoplasm and eccentrically located round and hyperchromatic nuclei. Smears prepared from aspirates of three fibrotic pancreata containing nodules of hyperplastic endocrine cells showed smaller fragments of endocrine-cell epithelium with focal gland-like arrangement. Individual hyperplastic endocrine cells displayed granular, filmy, and ill-defined cytoplasm and round to oval hyperchromatic nuclei showing a finely granular chromatin pattern. Nuclear pleomorphism was noted in some cell groups.     

Primary carcinosarcoma of the vagina

Primary carcinosarcoma of the vagina is a very rare tumor, with only eight cases diagnosed as carcinosarcoma in the literature that we are aware of. We recently encountered a case of primary carcinosarcoma of the vagina in a 75-year-old woman. The patient had a history of hysterectomy and bilateral ovariectomy for uterine corpus cancer at 55 years of age. Recurrence of the cancer was suspected 17 years after the operation and irradiation therapy was performed, but the patient died 3 years after the recurrence. Autopsy revealed a mass lesion in the pelvic cavity that originated in the vagina. Histological examination showed that the tumor contained anaplastic carcinoma, rhabdomyosarcoma, leiomyosarcoma and chondrosarcoma components, and it was diagnosed as carcinosarcoma. The histological diagnosis of the uterine corpus cancer was well-differentiated adenocarcinoma, and there was no sarcomatous component. The carcinosarcoma occurred 17 years after the hysterectomy, and it was concluded to be a primary carcinosarcoma of the vagina. This is the first case of primary vaginal carcinosarcoma in which the epithelial and sarcomatous components were clearly identified histologically and immunohistochemically.     

A unique pancreatic ductal adenocarcinoma with carcinosarcomatous histology, immunohistochemical distribution of hCG-beta, and the elevation of serum alpha-feto-protein

Pancreatic undifferentiated carcinomas with a neoplastic mesenchymal component (carcinosarcoma) have not been well described to date. The author experienced an autopsy case of a unique pancreatic ductal adenocarcinoma with carcinosarcomatous histology. The patient was a 90 year old Japanese male who died of cahexia with generalized tumor extension. Post-mortem examinations revealed some distinctive or representative components discerned in the tumor tissue. One was the well differentiated ductal adenocarcinoma. The second and the major finding was undifferentiated short spindle shaped or small round sarcomatous cells, which lacked an epithelial nature but showed positivity for CD10+, CD56+, Ki67++, p53++, and were focally positive for Desmin and vimentin. These two components were mixed and constituted the histology of the carcinosarcoma. In another area, anaplastic, large, pleomorphic tumor cells showed the focal immunohistochemical distribution of alpha-feto-protein and human chorionic gonadotropin. An ultrastructural study revealed adenocarcinoma cells with apical mucin secreting granules and well developed ductal differentiation, whereas undifferentiated sarcomatous cells showed primitive fibroblastic or mesenchymal characters without specific differentiation. Conclusively these findings suggested that this well differentiated adenocarcinoma gradually enlarged, accumulated genetic alternations, and then transformed into large and undifferentiated tumor cells, rapidly growing small sarcomatous cells, and a histology of carcinosarcoma.     

Microglandular endocervical hyperplasia and tubal metaplasia: Pitfalls in the diagnosis of adenocarcinoma on cervical smears

The detection of atypical glandular cells of undetermined significance (AGUS) has risen recently due to the use of new endocervical canal sampling devices, in particular the cytobrush. From April 1993–June 1994, a diagnosis of AGUS ranging from adenocarcinoma in situ (AIS) to invasive adenocarcinoma was initially made on cervical smears from 6 women for whom histologic follow-up data were available. The purpose of this study was to determine if benign cervical glandular lesions can be reliably distinguished from adenocarcinoma on cytology. Review of the smears and histologic slides from 3 patients showed microglandular endocervical hyperplasia on cervical cone specimens. Cervical smears from 2 of these patients showed clusters of small-to-medium-sized cells with nuclei containing coarse, granular chromatin and prominent nucleoli. Cytoplasmic vacuoles and engulfment of neutrophils were present, findings suggestive of endometrial adenocarcinoma. The third patient's smear showed clusters of large cells with ample, vacuolated cytoplasm and vesicular nuclei containing prominent nucleoli, findings suggestive of endocervical adenocarcinoma, In 3 cases evaluated by cervical conization, histologic slides showed tubal metaplasia. The cervical smears showed clusters and sheets of cells with round-to-oval-shaped nuclei containing evenly distributed, finely granular chromatin and inconspicuous nucleoli. Pseudoglandular formation was present in 2 cases, a finding suggestive of AIS. Since the cytologic features of microglandular endocervical hyperplasia and tubal metaplasia overlap those of adenocarcinoma, a differential diagnosis is prudent on cytologic smears of AGUS. Diagn. Cytopathol. 16:168–173, 1997. © 1997 Wiley-Liss, Inc.     

Cytological features of atypical carcinoid combined with adenocarcinoma of the uterine cervix

Neuroendocrine tumors of the uterine cervix (UC) are rare, and atypical carcinoid (AC) combined with adenocarcinoma of the uterine cervix (ACAUC) is particularly rare. Only the histopathology has been investigated in the English literature. A 49-year-old female with a polypoid lesion of the UC visited Yamanashi Prefectural Central Hospital. Scraping cytology, biopsy, and hysterectomy was performed. EC smears showed solid, rosette, honeycomb,true tubular, and trabecular clusters. Solid clusters were oval, thin-edge, delicate, small-large nuclei, pale, granular, scant, nothing,and well-preserved (though ill-defined border) cytoplasm. Rosette clusters were eccentric, oval nuclei, mixture of coarsely granular chromatin and euchromatin, and cyanophilic luminal content. Solid and rosette clusters impress AC. Honeycomb clusters involved a clearly defined border and translucent mucin. True tubular clusters were oval nuclei of fine chromatin or euchromatin, thick cytoplasm,and orange luminal content. Honeycomb and true tubular clusters suspected adenocarcinoma. Trabecular clusters were fusiform, columnar, cuboidal, and polygonal cell shapes of small,monotonous nuclei, and contained coarsely granular chromatin with occasionally intracytoplasmic translucent mucin and were difficult to differentiate typical carcinoid and adenocarcinoma.Histology was AC combined with adenocarcinoma. The aim of this study was to investigate the cytological characteristics of ACAUC.     

Minimal deviation endometrioid adenocarcinoma of the cervix: report of three cases with exfoliative cytology

Three histologically confirmed minimal deviation endometrioid adenocarcinomas (MDEA) of the uterine cervix with cytologic evaluation by cervical scraping were reviewed. The smears were cellular and showed tall columnar tumor cells arranged in monolayered sheets with nuclei in palisade at free borders, rosettes, and irregular clusters. Cellular strips with palisading nuclei was noted in one case. The individual tumor cells showed monomorphic, round or oval, hyperchromatic nuclei with chromatin clumping, small nucleoli, and granular, nonvacuolated cytoplasm with cytoplasmic extensions or tails. The smear background showed a variable amount of necrotic debris admixed with polymorphonuclear leukocytes in two cases. The cytologic manifestations of those three cervical MDEAs overlapped, to some extents, with those of a cervical adenocarcinoma in situ and with those of a well-differentiated endometrial adenocarcinoma invading the cervix.     

True pulmonary carcinosarcoma (squamous cell carcinoma and chondrosarcoma). A case report.

True pulmonary carcinosarcoma (squamous cell carcinoma and chondrosarcoma) originating in the right lower lobe in a 62-year-old Japanese male is reported. The tumor, measuring 5.5 x 3.5 x 3.5 cm, was markedly necrotic and its apex protruded into the bronchial lumen. Light microscopy showed that the tumor was composed of squamous cell carcinoma with sarcomatous spindle or polygonal cell proliferation and true chondrosarcoma. Immunohistochemically, the cytoplasm of numerous cells of the squamous cell carcinoma component was stained with anti-cytokeratin (PKK 1) and the cytoplasmic membrane with anti-epithelial membrane antigen (EMA). Although sarcomatous regions were stained with anti-vimentin (vimentin) and no tumor cells were reactive for EMA, a few tumor cells were positive for PKK 1. The cytoplasm of numerous chondrosarcoma cells was positively stained for vimentin and S-100 protein. Based on these findings, we concluded that the present tumor was a true carcinosarcoma composed of squamous cell carcinoma with sarcomatous regions and true chondrosarcoma.     

Eight cases of malignant mixed müllerian tumor (carcinosarcoma) of the uterus: Findings in surepath™ cervical cytology

Malignant mixed Müllerian tumor (MMMT)/carcinosarcoma is a rare neoplasm of the female genital tract characterized by a mixture of epithelial and mesenchymal components. There are published reports of conventional cervical smear findings in uterine MMMT, but to the best of our knowledge the cytomorphology of MMMT in SurePath? liquid‐based cytology samples has not been described. We present a series of eight cases of uterine MMMT in SurePath? cervical samples. The mean age of the women was 65.5 years (range, 60–82 years) and the most common presenting symptom was postmenopausal bleeding. Three out of the eight cases had both epithelial and sarcomatous elements in highly cellular cervical samples. In two cases, abnormal glandular cell clusters were closely associated with the mesenchymal component. The glandular component was usually represented by three‐dimensional clusters of malignant glandular cells and a dispersed population of large, round to oval malignant epithelial cells with single prominent nucleoli. Necrosis or tumor diathesis was not seen in any cases. Six out of the eight cases were initially reported as adenocarcinoma, endometrial type, and two cases as normal. Five cases had an atrophic background and tiny atypical glandular clusters that could easily be overlooked. Although cervical sample is not the method of choice for primary uterine carcinosarcoma screening, the possibility of the same should be kept in mind, when reporting a cervical sample from a woman with postmenopausal vaginal bleeding. Diagn. Cytopathol. 2014;42:165–169. © 2012 Wiley Periodicals, Inc.     

True Pulmonary Carcinosarcoma (Squamous Cell Carcinoma and Chondrosarcoma) A Case Report

True pulmonary carcinosarcoma (squamous cell carcinoma and chondrosarcoma) originating in the right lower lobe in a 62-year-old Japanese male is reported. The tumor, measuring 5.5×3.5×3.5 cm, was markedly necrotic and its apex protruded into the bronchial lumen. Light microscopy showed that the tumor was composed of squamous cell carcinoma with sarcomatous spindle or polygonal cell proliferation and true chondrosarcoma. Immunohisto-chemically, the cytoplasm of numerous cells of the squamous cell carcinoma component was stained with anti-cytokeratin (PKK 1) and the cytoplasmic membrane with anti-epithelial membrane antigen (EMA). Although sarcomatous regions were stained with anti vimentin (vimentin) and no tumor cells were reactive for EMA, a few tumor cells were positive for PKK 1. The cytoplasm of numerous chondrosarcoma cells was positively stained for vimentin and S-100 protein. Based on these findings, we concluded that the present tumor was a true carcinosarcoma composed of squamous cell carcinoma with sarcomatous regions and true chondrosarcoma Acta Pathol Jpn 42: 751–754, 1992.     

Immunohistochemical analysis of carcinomatous and sarcomatous components in the uterine carcinosarcoma: a case report

Uterine carcinosarcoma (malignant mixed Mullerian tumor) is an uncommon female genital tract neoplasm characterized by an admixture of epithelial and stromal malignant cells. We report a case of 50-year-old peri-menopausal woman diagnosed to have early-stage (IB due to FIGO) uterine carcinosarcoma of the homologous type with superficial (3mm) myo-invasion. The patient showed no clinical symptoms of the disease and had no family history of female genital tract malignancies. Positive immunostaining for steroid receptors (estrogen-alpha and progesterone receptors), cytokeratin, and EGFR was detected only in the carcinomatous area, whereas beta-catenin, BCL-2, COX-2, p16(INK4a), PTEN, RB-1, and vimentin were immunoreactive in both components. Androgen receptor, CD10, desmin, HER-2/neu, and P53 were found to be negative either in the carcinomatous or in the sarcomatous area. Tumor proliferative activity was higher in the carcinomatous (25%) than in the sarcomatous (2%) component. Based on these findings, immunohistochemical evaluation of multiple receptor status in the carcinomatous and sarcomatous areas of carcinosarcoma may provide a clue to the pathogenesis and hormonal receptor status of this uncommon uterine malignancy.     

Carcinosarcoma of the stomach. A case report with light microscopic, immunohistochemical, and electron microscopic study

A carcinosarcoma of the stomach in a 66-year-old man is reported. The tumor which had a diameter of 4 cm was an ulcerofungating mass in the posterior wall of the antrum. Histologically it was composed of well-differentiated adenocarcinoma admixed with sarcomatous elements which showed chondrocytic differentiation on light and electron microscopy. The sarcomatous areas were multifocally scattered in the central portion of the tumor and intimately blended with adenocarcinoma cells. CEA immunoreactivity was found not only in the adenocarcinoma but also in the transitional sarcomatous cells, supporting the hypothesis that this tumor might derive from mesenchymal metaplasia of a primarily epithelial neoplasm.     

Gastric carcinosarcoma with neuroendocrine differentiation as the carcinoma component and leiomyosarcomatous and myofibroblastic differentiation as the sarcomatous component

Gastric carcinosarcoma with neuroendocrine differentiation is a very rare neoplasm. In this article we present such a case. The gastroendoscopic examination of a 59-year-old Japanese man disclosed gastric cancer during follow-up after operation for rectal cancer. Subsequently, total gastrectomy was carried out because of gastric cancer. A large tumor measuring 9.2 x 8.4 cm was observed in the posterior wall of the upper portion of the stomach. The tumor was composed of carcinoma and sarcomatous cells, and the histological transition of both components was observed. Immunohistochemically, carcinoma and sarcomatous cells were positive for cytokeratin CAM5.2. The carcinoma contained adenocarcinoma and malignant cells with neuroendocrine differentiation. The sarcomatous component showed leiomyosarcomatous and myofibroblastic differentiation. The present tumor is the fifth case of gastric carcinosarcoma with neuroendocrine differentiation and the first case of gastric carcinosarcoma with myofibroblastic differentiation. Pathologists should bear in mind that gastric carcinosarcoma may show various types of differentiation.     

Peripheral primitive neuroectodermal tumor of the parotid gland region: report of a case with fine-needle aspiration findings

A case of peripheral primitive neuroectodermal tumor of the parotid gland region in a 38-yr-old woman is reported. She had a 1-yr history of a large, firm, and slightly tender left parotid-region mass. CT scan showed an invasive tumor involving the parotid gland, mandible, infratemporal fossa, and parapharyngeal space. Fine-needle aspiration cytology of the mass showed a highly cellular, poorly cohesive smear pattern exhibiting small cuboidal cells, with fibrillary cytoplasm forming occasional rosette-like structures. Numerous intact single cells with fragile cytoplasm, finely granular chromatin, and inconspicuous nucleoli were present together with free-lying nuclei in the background. Histologic, immunohistochemical, and ultrastructural findings confirmed the diagnosis. Diagn. Cytopathol. 2000;22:161-166. Published 2000 Wiley-Liss, Inc.     

Immunohistochemistry and K-ras sequence of pancreatic carcinosarcoma

Herein is presented a case of carcinosarcoma of the pancreas in an 82-year-old woman, analyzed on immunohistochemistry and K-ras sequence. The tumor, which arose in the pancreas head, was removed on pancreaticoduodenectomy. The patient died, however, of disseminated intravascular coagulation syndrome from postoperative sepsis 13 days later. Microscopically, the tumor consisted of malignant epithelial (well-differentiated adenocarcinoma cells) and mesenchymal (spindle-shaped tumor cells) components. The adenocarcinoma cells had positive immunostaining for cytokeratin AE1/AE3, cytokeratin 7, epithelial membrane antigen (EMA), CEA and carbohydrate antigen 19-9 (CA 19-9), while focal staining of these proteins was observed in the sarcomatous cells. In contrast, the sarcomatous cells had diffuse immunostaining for vimentin, CD10 and p53, while these proteins were not expressed in the ductal adenocarcinoma cells. These findings support the dual characteristics of a carcinosarcoma. DNA sequencing of the present case indicated point mutations of K-ras in both codons 12 and 34 on exon 2. The latter mutation is likely to correlate with the sarcomatous characteristics of this tumor. The tumor cells had specific and diffuse positive staining for CD10 and p53, with features characteristic of rapid growth.     

Exfoliative cytology of clear-cell sarcoma metastases in pleural fluid

Two cases of clear-cell sarcoma arising from the leg with widespread metastasis were reported. Exfoliated tumor cells in pleural effusions were round, oval, and slightly pleomorphic. They were seen singly or in clusters of variable size with marked cellular cohesiveness and molding. Their cytoplasm was well-defined, clear, or finely granular, and contained S-100 protein and periodic acid-Schiff positive material that was digestible by diastase. Tumor-cell nuclei were round and hyperchromatic with irregular chromatin clumping, and showed conspicuous nucleoli.     

Cytologic findings of acquired cystic disease-associated renal cell carcinoma: a report of two cases

Renal tumors may arise in the setting of end-stage renal cell disease. The risk is 100 times that of the normal population with an incidence ranging from 3-7%. The most common malignant tumor to arise in the setting of acquired cystic disease of the kidney is the acquired cystic disease-associated renal cell carcinoma (ACD-associated RCC). The cytomorphologic features of ACD-associated RCC, which has not been described previously, show moderately cellular specimens composed of clusters of cells with papillary configuration. The cells ranged from polygonal to columnar and contained abundant eosinophilic granular cytoplasm. The nuclei were round and centrally located, and the chromatin was finely granular with prominent central nucleoli that corresponded to Fuhrman's grade 3 nucleolar size. The main differential diagnosis is type 2 papillary renal cell carcinoma, from which it can be distinguished based on clinical findings only at this moment.     

Carcinosarcoma of the liver: a case report and review of the literature

No more than 11 cases of carcinosarcoma of the liver have been reported in the past 40 years that fulfill the definition of hepatocellular carcinoma combined with differentiated sarcomatous elements. Most cases consist of hepatocellular carcinoma with 1 to 2 heterologous elements. We report a case of a 51-year-old woman with liver carcinosarcoma consisting of 3 carcinomatous components and 4 sarcomatous components. Hepatocellular carcinoma, fibrolamellar type, was accompanied by neuroendocrine carcinoma (neuron-specific enolase and synaptophysin positive) and adenocarcinoma (cytokeratin 7 and 20 positive). The sarcomatous elements consisted of poorly differentiated spindle cell neoplasm (vimentin positive), leiomyosarcoma (smooth muscle actin positive), rhabdomyosarcoma (desmin positive), and osteosarcoma. To our knowledge, this is the first case of liver carcinosarcoma with this many differentiated heterologous features. There are differing views on the pathogenesis of this tumor. Findings in this case support the view that metaplasia of carcinomatous cells gives rise to the sarcomatous elements.     

Fine-needle aspiration cytology of pleuropulmonary blastoma: Case report and review of the literature

This report describes the fine-needle aspiration (FNA) cytology of a case of pleuropulmonary blastoma in a 3-yr-9-mo-old male. Pleuropulmonary blastoma is considered by most authors to be distinct from pulmonary blastoma and is a rare malignant tumor of the intrathoracic cavity. FNA smears were cellular with numerous small ovoid to spindled cells with oval to elliptical nuclei exhibiting finely granular chromatin and inconspicuous nucleoli. The cytoplasm was scant and cosinophilic with indistinct borders. Focal chondroid material and blastema-like cells were noted. The differential diagnosis suggested by the cytologic findings included rhabdomysosarcoma, teratoma, neuroblastoma, malignant mesenchymoma, pleuropulmonary blastoma, and metastatic tumor. To our knowledge, this is the first report of the cytology of this tumor. Diagn. Cytopathol. 16:336–340, 1997. © 1997 Wiley-Liss, Inc.     

Endometrial carcinoma recurring as carcinosarcoma: report of two cases

Endometrial carcinosarcoma is a rare, aggressive disease, accounting for approximately 3% of all uterine neoplasms. The emergence of sarcomatous elements is considered the evolution of subclones arising from high grade endometrial carcinomas. Here, we report two cases of primary endometrial carcinomas recurring as carcinosarcoma. Case 1. a 58-year-old postmenopausal woman diagnosed to have a poorly differentiated endometrial endometrioid adenocarcinoma (FIGO stage IB) developed an intra-abdominal recurrence of disease after 17 months from diagnosis. Histopathological analysis documented a biphasic neoplasia consisting of an epithelial (grade 3 endometrial endometrioid adenocarcinoma) and a sarcomatous component. Salvage chemotherapy with cisplatin, ifosfamide, epirubicin, and then with taxotere was attempted. The patient died after 2 months. Case 2. A 56-year-old woman with a diagnosis of grade 3 endometrial adenosquamous carcinoma of the endometrium (FIGO stage IIIA) experienced pelvic recurrence after five months from completion of chemotherapy. Definitive histology was malignant mixed mesodermal tumor with focal areas of chondrosarcomatous elements. The patient was triaged to exclusive concomitant chemoradiotherapy and salvage chemotherapy. The patient died after 3 months. We describe two cases of high grade endometrial carcinomas recurring as carcinosarcoma, thus providing evidence that the metaplastic sarcomatous evolution is a very rare event which can occur in patients with anaplastic endometrial cancer.