Transitional cell carcinoma with sarcomatous elements in the urinary tract. Six cases examined by immunohistochemistry.

We report six cases of carcinoma showing sarcomatous change in the urinary tract examined by conventional histochemistry and immunohistochemistry. All of the cases were transitional cell carcinoma with or without focal squamous cell carcinoma. Sarcomatous components resembling spindle cell sarcoma with a marked myxoid stroma or chondrosarcomatous element were also observed in all cases. The sarcomatous elements were closely associated with the areas of squamous cell carcinoma in three cases. Various histochemical staining procedures demonstrated mesenchymal features in the stroma of sarcomatous areas. By immunohistochemical examination, the epithelial components showed positive reactions for keratin, epithelial membrane antigen and, focally, carcinoembryonic antigen. The sarcomatous components revealed a positive immunoreaction for keratin but lacked other epithelial markers in all cases. Chondrosarcomatous elements in two cases were positive for both keratin and S-100 protein. These findings indicate that sarcomatous elements in carcinoma may represent mesenchymal metaplasia with partial or complete loss of epithelial features. However, further study will be necessary in order to determine whether heterogeneous elements, such as chondrosarcomatous areas, are epithelial or truly mesenchymal in origin.     

Usefulness of immunohistochemistry in delineating renal spindle cell tumours. A retrospective study of 31 cases

AIMS: To assess the usefulness of immunohistochemistry in delineating tumour diagnoses on a series of morphologically diagnosed renal spindle cell tumours (RSCTs). METHODS AND RESULTS: Formalin-fixed paraffin-embedded tissues from 31 morphologically diagnosed tumours were reinterpreted in light of newly obtained immunohistochemical information. By morphology, six had originally been classified as sarcomatoid carcinoma, five as spindle cell tumour (NOS), four as sarcoma (NOS), three as leiomyoma, three as leiomyosarcoma, and one each as fibrous polyp, hamartoma, neurilemmoma, mesoblastic nephroma, medullary fibroma, angiomyolipoma, haemangiopericytoma, malignant rhabdoid tumour, malignant Triton tumour, and carcinosarcoma. The application of immunohistochemistry verified the original diagnosis in 18 cases (18/31, 58%), confirming the diagnosis of sarcomatoid renal carcinoma (4/6), leiomyoma (2/3), leiomyosarcoma (3/3), sarcoma (NOS) (2/4), carcinosarcoma (1/1), malignant rhabdoid tumour (1/1), malignant Triton tumour (1/1), fibrous polyp (1/1), mesoblastic nephroma (1/1), hamartoma (1/1), and angiomyolipoma (1/1). Different tumour designations were suggested in 13 cases (13/31, 42%), including carcinosarcoma, sarcoma (NOS), leiomyosarcoma, solitary fibrous tumour, monomorphic/biphasic angiomyolipoma, endometrial stromal tumour, and congenital mesoblastic nephroma. CONCLUSIONS: Our data indicate that although morphology is most important in formulating the initial differential diagnosis, the addition of immunohistochemistry is vital in arriving at the correct classification of RSCTs.     

Analysis by comparative genomic hybridization of epithelial and spindle cell components in sarcomatoid carcinoma and carcinosarcoma: histogenetic aspects.

Sarcomatoid carcinomas and carcinosarcomas are histologically malignant biphasic neoplasms with an epithelial and a spindle cell component. Both a polyclonal and a monoclonal origin have been postulated for these tumours, but the latter has been favoured. For carcinosarcoma, the stem cell from which the epithelial and mesenchymal components are derived is expected to be more immature than the epithelial stem cell from which different components of sarcomatoid carcinoma originate, since in the latter, immunohistochemical or ultrastructural epithelial characteristics are still detectable. In the present study, comparative genomic hybridization was used to test the hypothesis that both tumour components in sarcomatoid carcinoma have more chromosomal aberrations in common than those in carcinosarcoma. From three sarcomatoid carcinomas originating from the urinary bladder and two carcinosarcomas from the pharynx, the epithelial and spindle cell components were microdissected and analysed for their respective chromosomal aberrations, using comparative genomic hybridization. High-level homology was seen in chromosomal aberrations between the different components in each tumour. This level of homology was even higher in the carcinosarcomas (65 and 91 per cent) than in both sarcomatoid carcinomas (21-51 per cent). The different phenotypic components of both sarcomatoid carcinoma and carcinosarcoma show a large overlap of chromosomal aberrations, strongly suggesting a monoclonal origin for all of these tumours. These findings do not support the hypothesis that the divergence between epithelial and spindle cell components occurs at an earlier stage in carcinosarcomas than in sarcomatoid carcinoma.     

Spindle and cuboidal renal cell carcinoma,a tumour having frequent association with nephrolithiasis: report of 11 cases including a case with hybrid conventional renal cell carcinoma/ spindle and cuboidal renal cell carcinoma components

AIMS: We present the largest series of an unclassified subtype of renal cell carcinoma, which seems to be a distinct morphological entity and which is sometimes designated as spindle and cuboidal renal cell carcinoma. METHODS AND RESULTS: Eleven cases of spindle and cuboidal renal cell carcinoma were found among 7000 primary renal cell tumours in Pilsen's routine and consultation files. The patients were five men and six women. They ranged in age from 22 to 65 years (mean 56.8). Microscopically, the tumours were composed of two main populations of cells. First, the preponderant type of cells was formed by flattened, spindle cells with sparse cytoplasm. The second cell type was a small cuboidal cell with clear to light eosinophilic cytoplasm. Spindle-shaped cells were arranged in a fascicular pattern often reminiscent of low-grade smooth muscle tumours. Solid areas of spindle cells were also present. Small cuboidal cells formed sparse tubular structures lined by a row of single cells. In addition to all previous published cases of spindle and cuboidal renal cell carcinoma we observed an association of nephrolithiasis in our cases. It was seen in 3/11 of our patients. A previously unreported feature is the occurrence of a conventional renal cell carcinoma component in one of our cases. Seven of our patients are currently well without signs of recurrence or metastasis, one had metastasis in a regional lymph node at the time of nephrectomy, one died of an unrelated condition, and two were lost to follow-up. CONCLUSIONS: We present 11 cases of spindle and cuboidal renal cell carcinoma, which is believed to be a distinctive morphological entity. Our cases were histologically, immunohistochemically and ultrastructurally similar to the previously reported cases of spindle and cuboidal renal cell carcinoma. In contrast to all previously reported cases of spindle and cuboidal renal cell carcinoma, we observed an association with nephrolithiasis in three of our cases; moreover, one of our tumours had a conventional renal cell carcinoma component and another revealed a metastatic focus in a regional lymph node. None of our patients died of the disease. This study confirms that spindle and cuboidal renal cell carcinoma has a low malignant potential.     

Primary hepatic lymphoma with spindle cell components: a case report

Diffuse large B-cell lymphoma (DLBCL) with spindle cell components is extremely rare and often misdiagnosed as carcinoma or sarcoma. Here, we present a case of primary DLBCL with spindle cell components arising in the liver, for which a preoperative diagnosis by needle biopsies was unsuccessful. The patient was a 70-year-old man with a continuous cough. Thoracic computed tomography incidentally detected a mass of 5 cm in diameter in his liver. The initial and second needle biopsies from the liver mass were pathologically diagnosed as suspicious for sarcomatoid hepatocellular carcinoma. He underwent an extended left hepatectomy. Histological examination revealed a diffuse or epithelioid arrangement of round and polygonal cells, mixed with the fascicles of spindle-shaped cells. Immunohistochemically, all the morphological types of tumor cells showed positive reactions for a lymphocytic marker (CD45RB) and B-cell markers (CD20 and CD79a). Double-immunostaining revealed that the spindle-shaped tumor cells expressed CD20, but never expressed alpha-smooth muscle actin. Malignant lymphoma with a spindle cell morphology is quite uncommon, and this variant can be a diagnostic pitfall, especially in tiny biopsy specimens. We emphasize that pathologists should be reminded of lymphoma as a differential diagnosis of spindle cell tumors.     

20例梭形细胞癌的病理形态及免疫组织化学特征

目的:探讨梭形细胞癌的形态学及免疫组织化学特征及鉴别诊断.方法:收集20例梭形细胞癌病例的临床及病理资料,分析其形态学特征及免疫表型特征.结果:20例梭形细胞癌中男性12例,女性8例,平均年龄62.5岁.肿瘤无器官特异性,肿瘤细胞呈梭形,多数病例异型性明显,少数病例细胞温和,异形性不明显.免疫组织化学示肿瘤细胞均表达vimentin;至少表达一种上皮标志物;CK,34pE12,CK5/6,EMA和P63阳性率较高;常表达desmin,calponin,SMA;不表达CD34,S100,HMB-45,myogenin,MyoD1,ALK.结论:梭形细胞癌是一种具有独特形态学和免疫表型的肿瘤.     

T cell rich B cell lymphoma (TCRBCL): study of sixteen cases with review of literature.

T cell rich B cell lymphoma (TCRBCL) is a recently described variant of diffuse non Hodgkin's lymphoma (NHL), the acronym of which has gained wide acceptance among hematopathologists in a relatively shorter period of time. The recognition of this entity requires immunohistochemical facilities especially on paraffin embedded tissues. TCRBCL is one of the many examples in the diagnostic anatomic pathology which emphasizes the need of immunocytochemistry and availability of this technique at least in referral laboratories. One of the differential diagnosis in this case includes lymphocyte predominance Hodgkin's disease (LPHD) which is the most favorable prognostic histologic subtype of Hodgkin's disease (HD) while TCRBCL is an aggressive B Cell NHL and should be treated as high grade large cell lymphoma. The other close differential includes peripheral T cell non-Hodgkin's lymphoma (PTCL). We reported sixteen (16) cases of TcRBCL diagnosed during a period of two and a half years (January 1995 to June 1997). HD and PTCL were the main differential diagnoses in most of these cases. The median age at diagnosis was 39 years and male to female ratio was equal. TCRBCL was nodal in location in 15 cases and a single case in extranodal site presenting as spinal tumor. The mean neoplastic B cell population was 12%, while that of reactive T cells was 82%. A significant polymorphous inflammatory cellular background was noted in 5 cases. Reed-Stenberg like cells were observed in 3 cases. Immunoglobulin light chain restriction studies were performed in fourteen cases and revealed lambda light chains in ten cases while in four cases kappa light chains were present.     

Mucinous tubular and spindle cell carcinoma of the kidney with neuroendocrine differentiation: report of two cases

We encountered 2 cases of mucinous tubular and spindle cell carcinoma (MTSCC) during a short time. In a 61-year-old man who had macroscopic hematuria for 1 month, the 14.5 x 14.0 x 12.0-cm resected tumor involved the right middle aspect of the renal parenchyma and compressed the renal pelvis. In an asymptomatic 47-year-old man, a renal tumor was found during an annual physical examination. The 3.5 x 3.0 x 2.0-cm tumor was located at the upper pole of the right kidney. The histologic findings in both cases were similar Tumors consisted of tightly packed, small, elongated tubules separated by pale mucinous stroma. The tumor cells were cuboidal to spindled with eosinophilic cytoplasm and low nuclear grade. Mitoses were few or nonexistent and without abnormal figures. Both tumors were immunoreactive for cytokeratin (CK) cocktail (AE1/AE3), high-molecular-weight CK (34betaE12), low-molecular-weight CK (35betaH11), CK7, epithelial membrane antigen, E-cadherin, and vimentin. The tumor cells also were reactive for neuron-specific enolase, chromogranin, and synaptophysin. The ultrastructure of the tumor cells contained abundant mitochondria, junctional complex, and dense-core neurosecretory granules. We present 2 additional cases of MTSCC showing typical morphologic features with neuroendocrine differentiation.     

Mucinous tubular and spindle cell carcinoma of kidney is probably a variant of papillary renal cell carcinoma with spindle cell features

Mucinous tubular and spindle cell carcinoma is a rare and newly described type of renal cell carcinoma (RCC) with a relatively indolent behavior. However, its histogenetic origin or line of differentiation remains unclear. Twelve cases of mucinous tubular and spindle cell carcinoma were identified and retrieved from the files of 3 institutions. Detailed morphological features, as well as their immunohistochemical profile established with markers of proximal renal tubules (RCC marker antigen, CD15, and alpha-methylacyl-CoA racemase) and of distal renal tubules (kidney-specific cadherin and cytokeratin 7), were studied. The age range of the patients was 35 to 73 years with a median of 56 years. The male to female ratio was 1:3. All of the patients were alive with follow-up between 4 and 38 months. All the tumors were confined to the kidney with a mean tumor size of 6.9 cm (range, 1.8-17 cm). The tumors were composed of variable proportions of tubular and spindle cell areas with focal to prominent mucinous or myxoid stroma. Foamy macrophages were seen in 10 cases and were prominent in 4 cases. A focal compressed tubulopapillary growth pattern was seen in 10 cases. The tumor cells were uniformly cuboidal with ovoid to round nuclei and inconspicuous nucleoli (Furhman nuclear grade 3 in 6 cases). Focal necrosis was seen in 3 cases. Immunostains showed that tumors were positive for RCC marker antigen (11/12), alpha-methylacyl-CoA racemase (11/12), CD15 (8/12), CD10 (2/12), kidney-specific cadherin (1/12), and cytokeratin 7 (11/12). Its morphological features as well as a strong preferential expression of proximal tubule markers suggest that this tumor is a type of RCC with proximal tubular differentiation, which appears closely related to or represents a morphological variant of papillary RCC.     

Renal mucinous tubular and spindle cell carcinoma: report of four cases and literature review

Mucinous tubular and spindle cell carcinoma of the kidney (MTSCC-K) is an unusual renal tumor. It is important to increase the recognition of the clinicopathological features of MTSCC-K and improve its clinical and differential diagnosis. This report described four cases of MTSCC-K with clinical, imaging, and pathological examination and showed that the tumor boundaries of MTSCC-K were clear, and tumor cells arranged into tubules and cord-like beams, between which was lightly stained myxoid stroma. The tumor cells were smaller and cube- or oval-shaped, with single small eosinophilic nucleoli, low-grade nuclei, and little nuclear fission. The myxoid stroma was scattered around lymphocytes and plasma cells. Immunohistochemical markers including CK7, CD117, EMA (epithelial membrane antigen), vimentin, and CK8/18, showed positive expression in tumor cells, but the tumor cells were negative for CD10 and villin. The proliferation index of Ki-67 was 5-10%. Since MTSCC-K is a rare low-grade malignancy, with unique histological and immunohistochemical characteristics, it is important for clinicians and pathologists to have a defined awareness of this tumor type in order to decrease the rate of misdiagnosis.     

Chordomas with malignant spindle cell components. A DNA flow cytometric and immunohistochemical study with histogenetic implications.

The authors studied four chordomas with malignant spindle cell components (SCs) and 12 conventional chordomas (CCs) by DNA flow cytometry using paraffin-embedded tissue. In addition, immunohistochemical stains for a variety of epithelial and mesenchymal markers were performed. The four SCs contained areas histologically identical to conventional chordomas, as well as a high-grade malignant spindle cell component. All four (100%) SCs had an aneuploid-multiploid DNA content. Of interest, the conventional chordoma areas in these tumors had DNA contents different from those containing the high-grade malignant spindle cells. In contrast, only three (27%) of the 11 conventional chordomas with analyzable histograms had an aneuploid-multiploid DNA content. Immunohistochemical studies performed on the four SCs showed the high-grade malignant spindle cells to stain strongly for vimentin and weakly for cytokeratin, S-100 protein, and epithelial membrane antigen (EMA), whereas the areas of conventional chordoma in these same neoplasms stained moderately for vimentin and S-100 protein, and strongly for cytokeratin and EMA. In two cases, the staining for EMA and cytokeratin highlighted a gradual transition between the areas of conventional chordoma and the spindle cell areas. The immunohistochemical staining pattern of the 12 conventional chordomas was similar to that seen in the conventional chordoma components of the four chordomas with malignant spindle cell components. These results suggest that: 1) aneuploidy is more common in SCs than in CCs, and 2) some SCs are multipotential neoplasms in which the neoplastic cells are capable of differentiation along both epithelial and mesenchymal pathways.     

Fine needle aspiration biopsy of renal mucinous tubular and spindle cell carcinoma: Report of two cases

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare renal tumor. Here we report two cases of MTSCC which were initially evaluated by fine needle aspiration biopsy (FNAB) and followed by surgical resection of the tumors. The cytomorphologic features of MTSCC were characterized by aggregates of relatively uniform, predominantly oval to spindle cells intermixed with abundant metachromatic myxoid matrix. Only rare epithelioid tumor cells with vacuolated cytoplasm were present. Immunohistochemically, the tumor cells were positive for CK7, CK19, CD10, vimentin, E‐cadherin, alpha‐methyl CoA racemase, and negative for CK903 and CK20. EMA and carbonic anhydrase IX immunoreactivity was seen in one of the two cases. Multiple chromosomal losses involving chromosomes 1, 2, 17 and likely chromosome 7 were revealed by fluorescence in situ hybridization (FISH). These cytomorphologic, immunophenotypic, and cytogenetic features were helpful for including this entity in the differential diagnosis of renal cell carcinomas. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

Pancreatic acinar cell carcinoma with pleomorphic and spindle cells: An autopsy-proven case

Pancreatic acinar cell carcinomas are glandular and have amphophilic/eosinophilic cytoplasm, presenting acinar, solid, and trabecular structures. Unusual histological features of acinar cell carcinoma are known, such as oncocytic, pleomorphic, spindle, and clear cell variants, but their clinical significance has not been well described. A man in his 70s was referred to our hospital because of elevated serum pancreatic enzymes. Contrast-enhanced abdominal computed tomography revealed slight swelling of the pancreatic head and suspension of the main pancreatic duct in the pancreatic body. He died only 14 days after admission. Gross findings at autopsy showed an ill-defined tumor located in the pancreatic head, involving the gastric and duodenal walls. Peritoneal dissemination, liver metastases, and lymph node metastases were also observed. Microscopically, tumor cells had moderate-to-severe nuclear atypia and amphophilic cytoplasm showing pleomorphism, and diffusely proliferated in solid pattern without lumina, were admixed with spindle cells. Immunohistochemically, tumor cells including pleomorphic and spindle cells were positive for B-cell lymphoma/leukemia 10 and trypsin. Consequently, the diagnosis was pancreatic acinar cell carcinoma with pleomorphic and spindle cells. We encountered a rare variant of pancreatic acinar cell carcinoma with pleomorphic and spindle cells. Clinically, our case showed rapid progression.     

Combined large cell neuroendocrine carcinoma and spindle cell carcinoma of the lung

We report a unique case of a combined pulmonary large-cell neuroendocrine carcinoma and spindle-cell carcinoma. The patient was a 54-year-old female smoker who presented with a 4-month history of increased left-sided chest pain and exertional dyspnea. The left upper lobectomy specimen revealed an 8.0-cm mass with central necrosis. Microscopically, the epithelial areas were composed of well-defined nests of large cells with peripheral palisading expressing low-molecular-weight keratin, synaptophysin, chromogranin, and neuron-specific enolase. The spindle-cell component consisted of pleomorphic cells arranged in fibrosarcoma and malignant fibrous histiocytoma-like patterns. These spindle cells were positive for low-molecular-weight keratin and vimentin with focal expression of CD68 and muscle-specific actin. Electron microscopy in the spindle-cell areas showed cell junctions and numerous tonofilaments, indicative of epithelial differentiation. The tumor behaved aggressively and the patient died with extensive metastases 4 months after surgery. The combination of neuroendocrine malignancies and spindle-cell carcinomas appears to be uncommon in the lung. Previous reports have described this association in single case reports of anaplastic small-cell carcinoma and atypical carcinoid, but not in large-cell neuroendocrine carcinoma.