The value of 'mesothelium-associated' antibodies in distinguishing between metastatic renal cell carcinomas and mesotheliomas

AIMS: Despite increasing usage of mesothelium-associated antibodies in diagnosis, a meta-analysis of studies analysing these antibodies in relation to distinguishing mesothelioma from renal cell carcinoma shows a paucity of published data. Given the clinical importance of elucidating this differential diagnosis, we compared the phenotypes of these two tumours using a panel of antibodies comprising recently described 'mesothelium-associated' antibodies and the more established 'epithelium-associated' antibodies. METHODS AND RESULTS: We applied an antibody panel comprising calretinin, cytokeratin (CK)5/6, thrombomodulin, carcinoembryonic antigen (CEA), BerEP4 and BCA225 to 37 cases of pleural mesotheliomas and 40 cases of renal cell carcinoma (27 primary tumours and 13 metastatic to the pleura). All mesotheliomas were either purely epithelioid or of mixed type. Cases of renal cell carcinoma were graded and classified as to cell type and architecture. For mesotheliomas, 0% stained for CEA, 16% for BerEP4, 83% for BCA225, 78% for CK5/6, 86% for thrombomodulin and 97% showed nuclear staining for calretinin. For renal cell carcinomas, 0% stained for CEA, 50% for BerEP4, 88% for BCA225, 5% for CK5/6, 32% for thrombomodulin and 10% showed nuclear staining for calretinin. CONCLUSION: Calretinin, CK5/6 and BerEP4 appear the most useful antibodies in helping to distinguish between renal cell carcinomas and mesotheliomas, although BerEP4 was not particularly sensitive for renal cell carcinomas. Thrombomodulin was not as specific as the other 'mesothelium-associated' antibodies in this study, reflecting how staining for mesothelium-associated antibodies varies in carcinomas from different primary sites, and such variations should be taken into account when assessing the differential diagnosis of mesothelioma. In cases where doubt remains over distinguishing metastatic renal cell carcinoma from mesothelioma, data from such a panel should be viewed with caution and assessed in association with clinical, imaging and morphological features.     

Value of mesothelial and epithelial antibodies in distinguishing diffuse peritoneal mesothelioma in females from serous papillary carcinoma of the ovary and peritoneum

AIMS: To evaluate the role of mesothelial markers (calretinin, thrombomodulin, cytokeratin 5/6, and CD44H) and carcinoma markers (polyclonal and monoclonal carcinoembryonic antigen, Leu-M1, CA-125 and Ber-EP4) in distinguishing diffuse peritoneal malignant mesothelioma from primary serous papillary adenocarcinoma of the ovary and peritoneum. METHODS AND RESULTS: Paraffin-embedded formalin-fixed blocks from 32 diffuse peritoneal mesotheliomas of epithelial subtype (all females), 20 serous papillary ovarian carcinomas and three primary peritoneal serous papillary carcinomas were studied. Calretinin and Ber-EP4 appeared to be the best positive mesothelial and carcinoma marker, respectively. Nuclear calretinin expression was identified in 28 of 32 malignant mesotheliomas with no nuclear immunoreactivity in the cohorts of serous papillary ovarian and peritoneal carcinomas, thus yielding 88% sensitivity and 100% specificity. Ber-EP4 showed 95% sensitivity and 91% specificity for serous papillary ovarian carcinoma. Thrombomodulin, cytokeratin 5/6 and CD44H immunoreactivities were seen in 18 (56%), 17 (53%) and 15 (47%) of peritoneal mesotheliomas, respectively, and in six (30%), five (25%) and five (25%) of the ovarian tumours, respectively. None of the three primary peritoneal serous papillary carcinomas expressed calretinin, thrombomodulin, cytokeratin 5/6 or CD44H. Polyclonal and monoclonal CEA, and Leu-M1 were expressed by two (10%), one (5%) and seven (35%) serous papillary ovarian carcinomas, respectively. None of the serous papillary peritoneal carcinomas expressed polyclonal CEA, monoclonal CEA or Leu-M1. CA-125 was positive in 19 (95%) and two (67%) ovarian and peritoneal carcinomas, respectively, and in eight (25%) peritoneal mesotheliomas. CONCLUSIONS: Calretinin and Ber-EP4 are useful discriminant markers in distinguishing peritoneal mesothelioma in women from serous papillary ovarian and peritoneal carcinoma. The other mesothelial markers (thrombomodulin, cytokeratin 5/6, and CD44H) and carcinoma markers (polyclonal and monoclonal CEA, and Leu-M1) yielded a too low sensitivity for practical use.     

Changing clinical course of patients with malignant mesothelioma: implications for FNA cytology and utility of immunocytochemical staining

The diagnosis of both local recurrences and distant metastases of mesothelioma can be accomplished by fine-needle aspiration (FNA) biopsy. Although the previous history of mesothelioma provides strong support for recurrent/metastatic mesothelioma, other diagnostic possibilities (particularly adenocarcinoma) may require exclusion via special stains in some cases. In this study, we report on the morphologic findings in 13 cases of mesothelioma which underwent FNA (7 metastatic lesions, 6 local recurrences). In addition, immunohistochemical staining results for 7 cases with available material using antibodies directed against cytokeratin AE 1/3 and two antibodies reported to show consistently positive results in mesothelioma (calretinin and cytokeratin 5/6) are reported and compared to results seen for 10 cases of adenocarcinoma. All cases of mesothelioma and adenocarcinoma showed strong staining with cytokeratin AE 1/3. Three of 7 cases of mesothelioma showed strong staining with calretinin, while only focal staining was detected in 3 additional cases; only one case showed positive staining with cytokeratin 5/6. One of 10 cases of adenocarcinoma showed calretinin positivity; however, at least focal staining with cytokeratin 5/6 was seen in 4 cases. These results suggest that cytokeratin 5/6 is neither a sensitive nor specific stain for the diagnosis of mesothelioma in cytology material. Calretinin appears to be more specific for mesothelioma but showed disappointing sensitivity for this tumor, potentially limiting its diagnostic utility in FNA material.     

SYT在诊断单相纤维型滑膜肉瘤中的价值

目的 探讨SYT在单相纤维型滑膜肉瘤(monophasic fibrous synovial sarcoma,MFSS)的诊断及与其它梭形细胞肿瘤鉴别诊断中的作用.方法 收集MFSS 36例、其它梭形细胞肿瘤32例,其中包括恶性外周神经鞘膜瘤7例、纤维肉瘤6例、平滑肌肉瘤4例、恶性纤维组织细胞瘤7例和孤立性纤维性肿瘤8例,检测sYT蛋白在上述病例中的表达.结果 SYT在MFSS中的阳性表达率为91.67%(33/36),其中15例呈弥漫强阳性表达(>80%的瘤细胞核呈强阳性),12例呈不同程度的阳性表达,50%～80%的瘤细胞核呈强阳性表达.SYT在其他梭形细胞间叶肿瘤中的阳性表达率为59.37%(19/32),其中6例呈弥漫强阳性表达(>80%的瘤细胞核呈强阳性),7例呈不同程度的阳性表达,50%～80%的瘤细胞核呈强阳性.结论 SYT蛋白在MFSS和其他梭形细胞肿瘤中均有较强的阳性表达,提示SYT抗体在MFSS与其他梭形细胞肿瘤的鉴别诊断中作用有限.     

Differential diagnosis of sarcomatoid mesothelioma from true sarcoma and sarcomatoid carcinoma using immunohistochemistry

Differentiation of sarcomatoid mesothelioma from other sarcomatoid tumors involving the pleura and other structures by light microscopy remains an important diagnostic challenge for surgical pathologists. The purpose of the present study was to investigate the utility of diagnostic immunohistochemistry for differentiating sarcomatoid mesothelioma from its histological mimics: true sarcoma and pulmonary sarcomatoid carcinoma. A total of 39 specimens of mesotheliomas with sarcomatoid components, 43 specimens of true sarcomas, and nine specimens of pulmonary sarcomatoid carcinomas were obtained from Japanese patients and examined using a 10-antibody panel (calretinin, WT1, AE1/AE3, CAM5.2, epithelial membrane antigen, desmin, α-smooth muscle actin, S-100 protein, CD34, and CD68). CAM5.2 had the highest sensitivity and specificity for differentiating sarcomatoid mesothelioma from true sarcoma. The combination of CAM5.2, WT1, and AE1/AE3 is recommended for routine pathological diagnosis. Accurate clinical information is necessary for differentiating sarcomatoid mesothelioma from sarcomatoid carcinoma.     

The diagnostic utility of immunohistochemistry in distinguishing between mesothelioma and renal cell carcinoma: a comparative study

Both mesotheliomas and renal cell carcinomas can present a wide variety of morphological patterns. Because of this, renal cell carcinomas that metastasize to the pleura and lung may be confused with mesotheliomas. The aim of the present study was to compare the value of the various immunohistochemical markers currently available for the diagnosis of mesothelioma and renal cell carcinoma. A total of 48 mesotheliomas (40 epithelioid, 8 sarcomatoid), and 48 renal cell carcinomas (24 conventional, 12 chromophobe, 8 papillary, 4 sarcomatoid) were investigated for the expression of the following markers: calretinin, mesothelin, cytokeratin 5/6, WT1, thrombomodulin (TM), N-cadherin, CD15 (leu-M1), MOC-31, Ber-EP4, BG-8 (Lewis(y)), CD10, renal cell carcinoma marker (RCC Ma), carcinoembryonic antigen (CEA), and B72.3. All (100%) of the epithelioid mesotheliomas reacted for calretinin, mesothelin, and cytokeratin 5/6; 93% for WT1; 78% for TM; 75% for N-cadherin, 48% for CD10, 15% for Ber-EP4, 8% for MOC-31, 8% for RCC Ma, 5% for BG-8, and none for CEA, B72.3, or CD15. Of the sarcomatoid mesotheliomas, 88% expressed calretinin, 75% N-cadherin, 38% CD10, and 13% each expressed cytokeratin 5/6, WT1, and TM. All of the remaining markers were negative. Among the RCCs, 81% expressed CD10, 75% N-cadherin, 63% CD15, 50% RCC Ma, 50% MOC-31, 42% Ber-EP4, 8% BG-8, and 2% TM. The remaining markers were negative. The results indicate that calretinin, mesothelin, and cytokeratin 5/6 are the best positive mesothelioma markers for differentiating epithelioid mesotheliomas from renal cell carcinomas. The best discriminators among the antibodies considered negative markers for mesothelioma are CD15, MOC-31, and RCC Ma. An accurate differential diagnosis can be reached with the use of any 2 of the 3 recommended positive markers, which should be selected based on availability and on which ones yield the best staining results in a given laboratory. One of the recommended negative markers may be added to the panel if deemed necessary. If confirmation of renal origin is needed, RCC Ma could be useful. Calretinin is the only marker that appears to have any utility in distinguishing between sarcomatoid mesotheliomas and sarcomatoid renal cell carcinomas.     

Mucinous tubular and spindle cell carcinoma with aggressive histomorphology--a sarcomatoid variant

Mucinous tubular and spindle cell carcinoma (MTSCC) is a recently described renal epithelial tumor. The bland cytomorphology of the spindled component and low-grade behavior help in its differentiation from sarcomatoid renal carcinoma. Sarcomatoid change has been reported in most histologic variants of renal cell carcinoma apart from MTSCC. Herein we report a case of an MTSCC in a 72-year-old female patient with high-grade spindled areas resembling fibrosarcomatous and undifferentiated pleomorphic sarcoma patterns with metaplastic bone. This index case also demonstrates a high proliferation index and extensive necrosis representing the first documented case of sarcomatoid change in MTSCC.     

Immunohistochemical marker panels for distinguishing between epithelioid mesothelioma and lung adenocarcinoma

The distinction between epithelioid mesothelioma and lung adenocarcinoma remains an important diagnostic challenge for surgical pathologists. The aim of the present study was to select a limited and appropriate panel of antibodies that can differentiate between epithelioid mesothelioma and lung adenocarcinoma. Specimens of 90 epithelioid mesotheliomas and 51 lung adenocarcinomas obtained from Japanese cases were examined using calretinin, WT1, AE1/AE3, CAM5.2, cytokeratin (CK) 5/6, vimentin, epithelial membrane antigen (EMA), thrombomodulin, CEA, CA19-9, and CA125. Ninety-six percent of epithelioid mesotheliomas were positive for calretinin; 99% for WT1; 100% for AE1/AE; 97% for CAM5.2; 70% for CK 5/6; 91% for vimentin; 96% for EMA; 71% for thrombomodulin; 77% for mesothelin; 7% for CEA; 17% for CA19-9; and 85% for CA125. In contrast, 33% of lung adenocarcinomas were positive for calretinin; 16% for WT1; 100% for AE1/AE3, CAM5.2, and EMA; 41% for CK 5/6; 47% for vimentin; 20% for thrombomodulin; 69% for mesothelin; 98% for CEA; 73% for CA19-9; and 80% for CA125. For distinguishing between epithelioid mesothelioma and lung adenocarcinoma, the combination of CEA, calretinin and each WT1 or thrombomodulin was suggested to be the best panel of immunohistochemical markers.     

Deciduoid mesothelioma in the pelvic cavity

A very rare case of deciduoid mesothelioma in the pelvic cavity is presented. A 24-year-old woman (gestational stage: 28 weeks and 6 days) was admitted because of a tumor mass in the abdominal cavity. A well-circumscribed and fibrously encapsulated tumor mass was revealed in the Douglas cavity. Histologically, tumor cells were arranged in a solid sheet with deciduoid appearance and showed partial glandular and papillary structures. The tumor cells contained PAS positive and diastase-digested granules in the cytoplasm as well as alcian-blue positive and hyaluronidase-digested substances in the stroma. The cellularity of the tumor cells was moderate and mitoses were rare. There was partial tumor necrosis and tumor cells had infiltrated through the fibrous capsule. Immunohistochemically, the tumor cells were reactive for pancytokeratin, cytokeratin5/6, vimentin, HBME-1, calretinin and thrombomodulin. Ultrastructurally, numerous, long microvilli, tonofilaments and desmosome junctions could be seen. Consequently, this case was diagnosed as deciduoid mesothelioma and 2 years and 4 months after operation, the patient's clinical course has been good. This case is considered to be the first reported in Japan.     

Mucinous tubular and spindle cell carcinoma of the kidney with sarcomatoid differentiation

We report a unique case of mucinous tubular and spindle cell carcinoma (MTSC) of the kidney with extensive sarcomatoid differentiation, multiple metastases, and a rapidly fatal clinical course. The patient presented with back pain and a pathologic L1 fracture. Diagnostic imaging revealed a large retroperitoneal mass arising from the left kidney and compressing the spinal cord. Radiotherapy and surgery were performed, but the patient died from disease progression three weeks postoperatively. MTSC is a recently recognized entity that is considered to be a low-grade carcinoma with a favorable prognosis. Our case demonstrates that although MTSC is usually a low-grade carcinoma, sarcomatoid differentiation may occur and lead to a fatal course, as in all other types of renal cell carcinomas. Adequate sampling and the exclusion of sarcomatoid differentiation in the spindle cell component are necessary for proper management and prognostication. To our knowledge, this is the first reported case of MTSC with sarcomatoid differentiation and a fatal outcome.     

Diagnostic utility of P63 and CD10 in distinguishing cutaneous spindle cell/sarcomatoid squamous cell carcinomas and atypical fibroxanthomas

The pathologic distinction of atypical fibroxanthomas (AFXs) from cutaneous spindle cell/sarcomatoid squamous cell carcinomas (SCSCCs) may occasionally pose a significant diagnostic challenge, given the substantial clinicopathologic overlap between these lesions. Recent studies indicate that p63 and CD10 are expressed in significant proportions of SCSCC and AFX, respectively. The purpose of this study is to investigate the utility of CD10 and p63 in distinguishing cutaneous SCSCCs and AFXs. The immunohistochemical expression of p63, CD10, cytokeratin AE-1/3, cytokeratin 5/6 and a cytokeratin cocktail (Kermix) was evaluated in an archived group of 23 AFXs and 10 SCSCCs. CD10 was positive in 18/23 AFXs (78%), with most demonstrating strong and/or diffuse staining. Three of 23 AFXs (13%), all negative for cytokeratins, showed focal and weak nuclear staining for p63. Two of 23 AFXs (9%) demonstrated very focal or weak staining for only one cytokeratin; in both cases, p63 and CD10 were negative. One AFX was negative with all immunostains. CD10 was positive in 6/10 SCSCCs (60%), with half demonstrating strong and/or diffuse staining. P63 was positive in 9/10 SCSCCs (90%), with most demonstrating strong and diffuse staining. One SCSCC was negative for p63, but positive with two cytokeratin immunostains. In conclusion, the expression of any of the cytokeratins evaluated herein significantly distinguished AFX from SCSCC. CD10 used in isolation, however, was not useful in making this distinction (positive in 18/23 AFXs versus 6/10 SCSCCs, p=0.4). The addition of CD10 to a panel that includes p63 did not provide any additional information to that obtained from the latter alone. Overall, the most effective combination to distinguish AFX from SCSCC was p63 and cytokeratin AE-1/3. Positivity for both p63 and cytokeratin AE-1/3 was seen in 9/10 SCSCCs (90%) and was not observed in any of the 23 AFXs (p<0.0001). The usefulness of CD10 in this differential diagnosis is limited.     

Pigmented spindle cell carcinoid tumour of the thymus with ectopic adrenocorticotropic hormone secretion: report of a rare variant and differential diagnosis of mediastinal spindle cell neoplasms

AIMS: A variety of histological variants of thymic carcinoid tumour have been described. A rare case of pigmented spindle cell carcinoid tumour of the thymus is documented and compared with the reported cases of thymic pigmented carcinoid tumour in the literature, with a discussion of the differential diagnosis of spindle cell tumours of the mediastinum. METHODS AND RESULTS: A thymic tumour with ectopic adrenocorticotropic hormone (ACTH) secretion was resected from a 24-year-old man suffering from Cushing's syndrome. Histological, immunohistochemical, and ultrastructural studies revealed an ACTH-producing spindle cell carcinoid tumour harbouring pigmented melanocytes. Among four thymic pigmented carcinoid tumours reported before, only one was similar to the present case by being also an ACTH-secreting pigmented spindle cell thymic carcinoid tumour. The clinicopathological features of this tumour distinguish it from a spindle cell thymoma, spindle cell thymic carcinoma, and other mediastinal spindle cell tumours. CONCLUSIONS: This case illustrates an extremely rare variant of thymic carcinoid tumour exhibiting a spindle cell morphology and harbouring pigmented melanocytes. Awareness of this histological variant is important in the differential diagnosis of spindle cell tumours of the mediastinum.     

Role of electron microscopy in the evaluation of soft tissue neoplasms, with emphasis on spindle cell and pleomorphic tumors

The current significant role of transmission electron microscopy in the evaluation of soft tissue tumors when correlated with conventional histological and immunohistochemical studies is discussed for the following entities: myxofibrosarcoma, storiform-pleomorphic fibrosarcoma (malignant fibrous histiocytoma), and myofibrosarcoma; dermatofibrosarcoma protuberans; hemangiopericytoma; monophasic synovial sarcoma; extrarenal rhabdoid tumor; soft tissue perineurioma; and gastrointestinal stromal tumors, notably the so-called autonomic nerve variant.     

Mucinous tubular and spindle cell carcinoma of kidney without sarcomatoid change showing metastases to liver and retroperitoneal lymph node

Mucinous tubular and spindle cell carcinoma (MTSCC) is an uncommon, newly recognized tumor that in its classic histological form shows tightly packed, elongated tubules with transition into spindle cell areas and pale mucinous stroma. The current data suggest that the great majority of MTSCCs have a favorable prognosis; however, the follow-up data are limited and the full biologic potential of this tumor remains to be established. There are a few examples of MTSCCs metastatic to lymph nodes and rare cases with sarcomatoid differentiation associated with distant metastases. We report on a case of MTSCC of kidney with concurrent nodal and liver metastases. The metastatic nodules were well circumscribed and showed morphological and immunophenotypic features similar to those of the primary tumor. Extensive sampling revealed no evidence of sarcomatoid morphology. To our knowledge, this is the first case of MTSCC without sarcomatoid differentiation showing parenchymal metastasis.