Heterogeneity of epithelial marker expression in routinely processed, poorly differentiated carcinomas.

The application of immunohistochemical markers against epithelial antigens has proved useful for studying tumor differentiation and in aiding tumor diagnosis. However, the reactivity of various epithelial markers with poorly differentiated carcinomas (the situation in which they are most often used) has not been well established. As a result, it is unclear how negative results should be interpreted and how often more than one antibody may be needed to document the epithelial nature of poorly differentiated neoplasms. We studied 98 poorly differentiated epithelial tumors with AE1, CAM 5.2, and EMA to assess the use of these markers in their diagnosis. Both CAM 5.2 and EMA provided support for epithelial differentiation in 71% (70/98) of the cases, while AE1 stained 50% (49/98) of the tumors; CAM 5.2 was the single most useful marker in the subset of poorly differentiated neuroendocrine carcinomas, staining 20 (77%) of 26 tumors. Use of these markers in pairs increased the recognition of epithelial differentiation (at least one marker showing positive staining) as follows: AE1/CAM 5.2, 80% (78/98); AE1/EMA, 87% (85/98); and CAM 5.2/EMA, 99% (97/98). Thirty carcinomas stained with all three markers, 34 with two markers, and in 34 cases only one antibody supported epithelial differentiation. Twelve (21%) of 58 tumors showed evidence of S100 reactivity. None of the 71 cases to which PD7 was applied showed staining This study indicates that poorly differentiated carcinomas are heterogeneous in their expression of antigens recognized by AE1, CAM 5.2, and EMA. Moreover, these results quantitate the probability of reactivity with poorly differentiated carcinomas for each marker and support the use of one or more antibodies in a "backup" panel when a negative result is obtained with a single antibody and the diagnosis of carcinoma is still suspected.     

Wide spectrum screening keratin as a marker of metaplastic spindle cell carcinoma of the breast: an immunohistochemical study of 24 patients

Wide spectrum screening keratin as a marker of metaplastic spindle cell carcinoma of the breast: an immunohistochemical study of 24 patients
Aims : Metaplastic spindle cell carcinomas may be difficult to distinguish histologically from other spindle cell lesions in the breast. Variable staining with cytokeratin immunomarkers has been reported for metaplastic carcinomas. We evaluated the diagnostic utility of anti-cytokeratin polyclonal antibody, wide spectrum screening keratin, to assess spindle cell breast lesions.
Methods and results : Twenty-four patients with spindle cell breast carcinoma and 31 patients with benign or malignant spindle cell tumours were studied using a panel of antibodies directed against multiple cytokeratins (AE1/AE3, CAM5.2, wide spectrum screening keratin), epithelial membrane antigen (EMA), and vimentin. Sites of origin for the 31 controls included breast, bone, and soft tissue. All but one (95.8%) metaplastic carcinomas stained positively with wide spectrum screening keratin. Only rare or focal immunoreactivity was observed with AE1/AE3 in four cases; however, sensitivity of AE1/AE3 was improved in 13 cases using steam EDTA as an antigen retrieval technique. Three cases were immunoreactive with CAM5.2 and eight cases were immunoreactive with EMA. All control cases lacked immunoreactivity with the cytokeratin panel and EMA. The spindle cells in the metaplastic breast tumours (88%) and in the controls (97%) stained with vimentin.
Conclusions : Wide spectrum screening keratin may be the most useful and convenient antibody in differentiating metaplastic spindle cell carcinoma from other spindle cell lesions in the breast.     

Ber EP4 and epithelial membrane antigen aid distinction of basal cell, squamous cell and basosquamous carcinomas of the skin

AIMS: Seventy-five skin tumours were studied to investigate the value of immunohistochemistry in differentiating basal cell, squamous cell and basosquamous carcinomas of the skin. METHODS AND RESULTS: Archived paraffin-embedded tissue samples of basal cell carcinomas (n = 39), squamous cell carcinomas (n = 23) and basosquamous carcinomas (n = 13) were stained immunohistochemically using a panel of antibodies. All of the basal cell carcinomas stained positively for Ber EP4, in contrast to the group of squamous cell carcinomas, that showed no staining. Basosquamous carcinomas all showed at least some areas of Ber EP4 positivity. None of the basal cell carcinomas, but most of the squamous cell carcinomas (22 of 23) expressed epithelial membrane antigen (EMA). Only one of the basosquamous carcinomas expressed EMA positivity focally. CAM 5.2, carcinoembryonic antigen (CEA) and 34betaE12 antibodies lacked specificity in relation to the different tumour types. CONCLUSION: Distinction of basal and squamous cell carcinomas of the skin can be readily achieved with routine immunohistochemistry using Ber EP4 and EMA. Identification of basosquamous carcinoma is also facilitated with this method.     

Immunohistochemical study of 158 lung carcinomas.

Lung carcinomas were studied immunohistochemically and the results were related to type of tissue sample (bronchoscopic biopsies, surgical specimens, autopsies). All cytokeratins (CAM 5.2, PKK-1, AE1/AE3) reacted with virtually all adenocarcinomas, most squamous, and 65% of the large cell carcinomas, while CAM 5.2 was most efficient with the small cell carcinomas. CEA stained 33% and 60% of the small and large cell carcinomas, respectively, most adenocarcinomas, and 84% of the squamous cell carcinomas, among which staining decreased with dedifferentiation and was often focal. EMA reacted with 90%, and NSE with 20% of all histological types. There was no staining for NF. All antibodies, except EMA, were more efficient with surgical specimens. Our study implies that the cytokeratins we used work better with surgical material, but are generally comparable to monospecific cytokeratin antibodies. Also, EMA is a reliable marker for epithelial differentiation with all types of tissue samples. Moreover, CEA negativity in several poorly differentiated lung carcinomas might have implications in the differential diagnosis against pleural mesothelioma.     

Utility of immunohistochemistry in distinguishing ovarian sertoli-stromal cell tumors from carcinosarcomas.

Poorly differentiated Sertoli-stromal cell tumors and carcinosarcomas of the ovary both show biphasic epithelial and stromal patterns and may both show heterologous stromal elements, presenting a difficult diagnosis. We studied the immunohistochemical profile of Sertoli cell differentiation in human testes and applied these findings to the ovarian tumors. Eleven Sertoli-stromal cell tumors, six carcinosarcomas of the ovary, and 11 testes (six fetal, one infant, and four adult) were studied using antibodies to cytokeratin AE1:AE3 (AE1:3), cytokeratin CAM 5.2 (CAM), epithelial membrane antigen (EMA), vimentin, desmin, muscle-specific actin (MSA), S-100 protein (S-100), CA 19-9, CA 125, carcinoembryonic antigen monoclonal (CEA-M), carcinoembryonic antigen polyclonal (CEA-P), and placental alkaline phosphatase (PLAP). In the fetal testes, immature gonadal stroma and sex cord areas stained with vimentin (six of six cases), AE1:3 (five of six cases), and CAM (six of six cases). Sertoli cells in immature gonadal stroma areas, sex cords, and seminiferous tubules of normal fetal, infant, or adult testes never showed immunoreactivity for EMA, S-100, CA 19-9, CA 125, CEA-M, CEA-P, or PLAP. All Sertoli-stromal cell tumors stained with AE1:3 and CAM in areas of Sertoli cell differentiation (11 of 11 cases) but did not stain with EMA, PLAP, CEA-P, CEA-M, CA 19-9, CA 125, or S-100 (none of 11 cases). Carcinosarcomas expressed AE1:3 and CAM in all epithelial areas (six of six cases) and most stromal areas (five of six cases). Carcinomatous areas of carcinosarcoma also showed immunoreactivity for EMA (six of six cases), CA 125 (two of six cases), PLAP (two of six cases), CEA-P (two of six cases), and CEA-M (one of six cases), while stromal areas of carcinosarcoma expressed EMA (four of six cases) and S-100 (four of six cases). Heterologous stromal elements were present in three of 11 Sertoli-stromal cell tumors (two showed skeletal muscle and one showed both skeletal muscle and cartilage differentiation) and in four of six carcinosarcomas (one skeletal muscle, one cartilage, and two cartilage and skeletal muscle). All skeletal muscle heterologous elements expressed desmin, vimentin, and MSA. The heterologous cartilage in carcinosarcoma stained with S-100 (three of three), while the one case of heterologous cartilage in Sertoli-stromal cell tumor did not. These results suggest that ovarian Sertoli-stromal cell tumor can be distinguished from carcinosarcoma by the absence of staining for EMA, PLAP, CEA, CA 125, or CA 19-9 in epithelial areas of Sertoli-stromal cell tumor.(ABSTRACT TRUNCATED AT 400 WORDS)     

Keratins versus epithelial membrane antigen in tumor diagnosis: an immunohistochemical comparison of five monoclonal antibodies

Among the monoclonal antibodies capable of detecting epithelial lineage, some recognize keratin and others identify antigens of epithelial membranes. Of the latter, the most commonly used is directed against an antigen present in cell membranes derived from milk fat globules, epithelial membrane antigen (EMA). To determine their relative sensitivity and specificity and hence their diagnostic value, we compared four commercially available monoclonal antibodies to low-molecular-weight keratins--AE1, CAM 5.2, PKK1, and 35 beta H11--with the monoclonal antibody to EMA (anti-EMA). We studied 383 samples of human neoplasms of diverse histogenetic types and degrees of differentiation. Anti-EMA was found to be less sensitive than the monoclonal antibodies to keratin in several epithelial tumors, including tumors of the prostate (11 of 13 negative), gastrointestinal tract (13 of 34 negative), and thymus (seven of eight negative). Anti-EMA was also less sensitive in mesotheliomas (nine of 24 negative). Of the embryonal carcinomas, all stained with the monoclonal antibodies to keratin, whereas none stained with anti-EMA. False-positive staining with anti-EMA was seen in two of 14 T-cell lymphomas. We conclude that the monoclonal antibodies to low-molecular-weight keratins are more sensitive and specific for the identification of epithelial origin of neoplasms than is monoclonal anti-EMA. Anti-EMA should not be used as the sole marker of epithelial differentiation in tumor diagnosis.     

Cytokeratin expression in adrenocortical neoplasia: an immunohistochemical and biochemical study with implications for the differential diagnosis of adrenocortical, hepatocellular, and renal cell carcinoma.

The immunostaining patterns of adrenocortical tumors are not clearly defined, primarily due to their inconsistent expression of cytokeratins (CK). To address this issue and to investigate whether adrenocortical tumors can be immunohistochemically differentiated from histologically similar tumors arising from the kidney and liver, we studied four normal adrenal glands, two adrenocortical adenomas (ACAs), 31 adrenocortical carcinomas (ACCs), 37 renal cell carcinomas (RCCs), and 33 hepatocellular carcinomas (HCCs) with anti-CK antibodies AE1, CAM 5.2, UCD/PR10.11, 35BH11, PKK1, and Ks19.1, as well as antibodies to vimentin (VIM), epithelial membrane antigen (EMA), and HMFG-2. Normal adrenal cortical cells showed variable staining with all anti-CK antibodies on fixed and frozen sections. In contrast, only one of two fixed ACAs stained with a single anti-CK, although both neoplasms reacted with multiple anti-CK antibodies on frozen sections. Similarly, 20 of 31 fixed ACCs contained VIM, but only one tumor stained for CK; frozen sections of this and another, previously negative tumor, however, stained with most of the anti-CK antibodies tested. One-dimensional Western immunoblot analysis confirmed the presence of CKs 18 and 19 in two examples of normal adrenal cortex, one ACA, and the ACC immunohistochemically positive on fixed and frozen sections, with CK 19 identified in the ACC that was positive on frozen section alone. All fixed HCCs and most RCCs stained with multiple anti-CK antibodies (33 and 34 cases, respectively), with a proportion of tumors positive for VIM (six and 22 cases, respectively), EMA (seven and 30 cases, respectively), and HMFG-2 (15 and 28 cases, respectively). The results suggest that CK expression is diminished in most adrenocortical tumors to levels too low to be recognized following the deleterious effects of fixation. While the immunohistochemical absence of CK, EMA, and HMFG-2 in fixed sections in the majority of ACCs is distinctive, sufficient phenotypic overlap exists such that differentiation between RCC and HCC may not be possible in an individual case.     

Vimentin is preferentially expressed in high-grade ductal and medullary, but not in lobular breast carcinomas.

Two hundred sixty-two invasive breast carcinomas dating from 1979 to 1984 were tested for vimentin and keratin on formaldehyde-fixed paraffin-embedded sections. None of 26 lobular carcinomas expressed vimentin. Vimentin expression in 10% or more of tumor cells was found in 78% of medullary (14 of 18), in 16% of ductal not otherwise specified (NOS) (35 of 214), and in two of four mucinous carcinomas. A further seven tumors showed vimentin expression in less than 1% to 10% of the cells. Vimentin was expressed in tumor cells of 30% (28 of 93) of grade III invasive ductal NOS carcinomas versus 7% (7 of 105) of grade II and 0% of grade I carcinomas (0 of 10). Vimentin was found to be preferentially expressed in tumors growing in broad, often anastomosing bands or sheets with extensive necrosis, scanty supportive stroma, high nuclear grade, and numerous mitoses. The authors conclude that vimentin is not detected in lobular carcinomas, but is preferentially expressed in medullary and in high-grade ductal NOS breast carcinomas.     

Evaluation of epithelial and keratin markers in glioblastoma multiforme: an immunohistochemical study.

OBJECTIVE: Poorly differentiated metastatic carcinoma may be difficult to distinguish histologically from high-grade astrocytic malignant neoplasms, particularly on small open or stereotactic biopsy specimens. Previous authors have reported that a subset of glioblastoma multiforme (GBM) variably stains with cytokeratin immunomarkers. The authors examined a panel of epithelial and keratin antibodies by paraffin immunohistochemistry to evaluate the immunophenotype of GBM for these markers and to determine what combination of immunostains would be optimal in distinguishing GBM from metastatic carcinoma. METHODS: Twenty-three patients with GBM (age range, 19-86 years; mean, 63.4 years; 14 men and 9 women) and 22 patients with metastatic carcinoma (age range, 26-77 years; mean, 58.1 years; 7 men and 15 women) to the brain were studied with a panel of immunostains, including glial fibrillary acid protein (GFAP), Ber-EP4, antikeratin monoclonal antibodies AE1/3, and antibodies to CAM 5.2 and cytokeratins 7 (CK7) and 20 (CK20). Sites of origin for the metastatic tumors included lung (n = 11), breast (n = 5), endometrium (n = 1), prostate (n = 1), colon (n = 1), presumed kidney (n = 1), and unknown (n = 2). RESULTS: All GBMs stained positive for GFAP (100%), and all but 1 (95.7%) stained positive for cytokeratins AE1/3. Only rare focal immunoreactivity was observed in a single case of GBM with CAM 5.2 (4.3%), CK7 (4.3%), and CK20 (4.3%). Immunoreactivity with Ber-EP4 was not observed in any of the GBMs (0.0%). All cases of metastatic carcinoma stained positive with cytokeratins AE1/3 (100%) and CAM 5.2 (100%). Variable staining was observed in carcinomas with CK7 (17 of 22, 77.3%), Ber-EP4 (11 of 22, 50.0%), and CK20 (9 of 22, 40.9%). Three metastatic carcinomas showed rare GFAP-positive staining cells (13.6%). CONCLUSIONS: Based on the aforementioned results, a combination of immunostains, including GFAP and cytokeratin CAM5.2, may be the most useful in differentiating poorly differentiated metastatic carcinoma from GBM. A significant number of GBMs stain with some cytokeratin markers, in particular cytokeratins AE1/3. Because of the poor specificity of cytokeratins AE1/3 in distinguishing metastatic carcinoma from GBM, it should not be used to differentiate the 2 entities.     

Immunohistochemical examination of 25 cases of Merkel cell carcinoma: a comparison with small cell carcinoma of the lung and oesophagus, and a review of the literature.

Merkel cell carcinomas (MCC) were compared to small cell carcinomas of the lung (SCCL) and oesophagus (SCCO). Most MCC were of the intermediate cell type while SCCL and SCCO were usually of the small cell type. Only MCC of trabecular type could be separated from SCCL and SCCO by means of histopathological examination alone. All MCC (25) stained with cytokeratin CAM 5.2, 20 of which in a "paranuclear globular" or combined "paranuclear globular"/diffuse pattern while 17 MCC stained with cytokeratin AE1/AE3. Cytokeratin CAM 5.2 reacted with 60 percent of the SCCL and 86 percent of the SCCO, and cytokeratin AE1/AE3 with 33 and 28 percent respectively. Neurofilament stained 17 MCC in a "paranuclear globular" pattern but none of the SCCL and SCCO. All MCC with a diffuse staining pattern for cytokeratin CAM 5.2 were negative for neurofilament. The results of this study and review of the literature indicate that in most instances Merkel cell carcinoma can be separated from other SCC, pulmonary as well as extrapulmonary, by means of histopathological and, above all, immunohistochemical examinations.     

Comparison of keratin monoclonal antibodies MAK-6, AE1:AE3, and CAM-5.2

Two routinely used antikeratin monoclonal antibodies, AE1:AE3 (Hybritech Inc., La Jolla, CA) and CAM-5.2 (Becton-Dickinson, Mountain View, CA), were compared with a new antikeratin monoclonal antibody mixture, MAK-6 (Triton Biosciences, Inc., Alameda, CA). Various poorly differentiated epithelial neoplasms, lymphomas, melanomas, and sarcomas were studied with the use of the avidin-biotin-peroxidase technic. All three antibodies had similar staining profiles, however, some differences were noted. The MAK-6 and CAM-5.2 antibodies illustrated stronger staining for some grade III transitional cell carcinomas, whereas the AE1:AE3 was variably positive to negative in all cases. Three renal cell carcinomas were positive with all three antibodies, two were negative with all three, and one had scattered positive cells with MAK-6 only. All lymphomas and plasmacytomas were negative with MAK-6 and CAM-5.2, however, AE1:AE3 faintly stained two of three plasmacytomas and two of the seven large cell lymphomas. Two out of three hepatomas evaluated were strongly positive with CAM-5.2 and MAK-6 and variably positive with AE1:AE3. The third case had both positive and negative cells with all three antibodies. In conclusion, MAK-6 antikeratin antibody is as useful as AE1:AE3 and CAM-5.2 for identification of poorly differentiated epithelial neoplasms.     

Immunohistochemical Study of Cytokeratin Distribution in the Collecting Duct of the Human Kidney

In order to assess the expression of different cytokeratins in the collecting duct cells (CDCs) of the human kidney, three consecutive sections were stained with periodic acid-Schiff, CAM 5.2, and AE-1 (CAM 5.2 recognizes cytokeratins #19,18,8 and AE 1 #19,16,15,14,10 of Moll's catalog.), respectively. By comparing these sections, it was found that most CDCs in the inner medulla were both CAM 5.2 and AE 1 positive, whereas in the outer medulla and cortex, 77% of the CDCs were both CAM 5.2 and AE 1 positive, 15% CAM 5.2 positive and AE 1 negative, 8% both CAM 5.2 and AE-1-negative, and 0.4% CAM 5.2 negative and AE 1 positive. Recent studies have shown that most CDCs express low-molecular weight cytokeratins #7,8,18 and 19(17,18,19,20). Of these cytokeratins, CAM 5.2 recognizes cytokeratins #8,18,19 and AE-1 recognizes cytokeratin #19. Therefore, most CDCs belong to one of the following three major types; 1. Those positive for cytokeratins #8,18 and 19 (CAM 5.2 and AE 1 positive), 2. Those positive for cytokeratins #8 and 18 and negative for #19 (CAM 5.2-positive and AE 1 -negative) and 3. Those negative for cytokeratins #8,18 and 19 (CAM 5.2 and AE 1 negative). A few CAM 5.2 negative and AE 1 positive cells were thought to express high molecular weight cytokeratins. The significance of these various cytokeratin expressions is discussed. Acta Pathol Jpn 41: 516 520, 1991.     

An immunohistochemical study of metaplastic spindle cell carcinoma, phyllodes tumor and fibromatosis of the breast

The diagnosis of metaplastic (sarcomatoid) carcinoma (MSC) of breast often requires immunohistochemistry with a cytokeratin (CK) panel to distinguish them from phyllodes tumors (PT), primary sarcomas, and fibromatoses. CK staining may be heterogeneous in metaplastic carcinomas. The aim of the study was to investigate the theory that MSCs show evidence of myoepithelial differentiation and to evaluate immunohistochemical markers that may be helpful in distinguishing MSCs from PT and fibromatosis. We reviewed histology and performed immunohistochemistry for AE1/AE3, 34betaE12, CK5 and CK14, Cam5.2, CK7 and CK19, epithelial membrane antigen (EMA) (B55), smooth muscle actin (SMA), S100, desmin, vimentin, CD31, CD34, and bcl-2 on paraffin-embedded tissue from 18 MSCs, 26 PTs, and 8 fibromatoses. We assessed staining by using a semiquantitative method. Sarcomatous areas in MSCs were positive for 34betaE12 in 11 cases; for SMA in 10; for CK5 in 7; for CK14 in 6; for Cam5.2, AE1/AE3, and S100 in 5; and for CK7 and CK19 in 3. No CK expression was seen in stromal areas in PT or in fibromatoses. CD34 and bcl-2 were more frequently expressed in spindle cell areas in PTs (18 and 12 of 26, respectively) than in MSCs (0 and 2 of 18, respectively). MSCs show strong evidence of myoepithelial differentiation. CD34 and, to a lesser extent, bcl-2 positivity in PTs may be helpful in differentiating these two lesions from MSCs, particularly in small biopsies, because CK staining in MSCs may be heterogeneous. In our hands, 34betaE12 was the CK most frequently expressed in sarcomatoid areas in MSCs.     

Clear cell carcinoma of testis: A review

Clear cell Mullerian-type adenocarcinoma of the testis is an exceedingly rare entity, and its histogenesis and clinical behavior are still poorly understood. We discuss three cases of clear cell carcinoma of the testis, compiled from a review of the literature and our personal experience. Microscopically, the tumors closely resembled clear cell carcinoma of the ovary, displaying papillae lined by clear cells with areas of hobnailing. The reported immunophenotypic features were also similar to that of ovarian tumors, as positivity for epithelial markers (CK7, CAM5.2, AE1/AE3, EMA) and Mullerian markers (PAX8, CA125) with negativity for estrogen and progesterone receptors have been observed. The pathogenesis of testicular clear cell carcinoma is still poorly understood, with reported cases displaying evidence of both mesothelial and Mullerian origin. In addition, molecular characterization of testicular clear cell carcinomas has yet to be accomplished; however, studies performed on ovarian clear cell carcinomas may provide insight to the origin, biologic behavior, and potential therapeutic modalities for this obscure, aggressive malignancy.     

Immunoperoxidase staining as a diagnostic aid for hepatocellular carcinoma

Hepatocellular carcinoma may share histologic features with a wide variety of epithelial tumors. To facilitate its pathologic diagnosis, clinical and pathologic material was reviewed from 62 patients with hepatocellular carcinoma and immunostaining was performed with polyclonal anti-carcinoembryonic antigen (pCEA), monoclonal anti-carcinoembryonic antigen (mCEA), anti-epithelial membrane antigen (EMA), and an antikeratin (KER AE1/AE3). Clinical information and follow-up were available for all patients from several sources. Cases with ambiguous clinical data or findings suggestive of metastatic carcinoma to the liver were excluded. In addition, the following tumors were immunostained and compared to hepatocellular carcinoma: 10 cholangiocarcinomas; 14 pancreatic adenocarcinomas; 4 gastric adenocarcinomas; 3 breast carcinomas; 5 renal carcinomas; 3 combined germ cell tumors of the testis; 3 adrenal cortical carcinomas; and 4 melanomas. The pCEA stained bile canaliculi in normal liver and in 39 of 62 (63%) hepatocellular carcinomas. This canalicular staining pattern of pCEA was unique to hepatocellular carcinoma. The mCEA (1 of 62, 1.6%) was almost always negative, and KER AE1/AE3 (9 of 59, 15.3%) was occasionally positive. The EMA stained 25 of 62 (40.3%). The adrenal cortical carcinomas and melanomas were negative for all antigens except rare pCEA and focal EMA staining in an adrenal tumor. Other carcinomas showed cytoplasmic pCEA (36 of 44, 81.8%), mCEA (40 of 46, 87.7%), EMA (41 of 43, 95.4%), and KER AE1/AE3 (42 of 44, 95.5%). Canalicular staining with pCEA is specific for hepatocellular carcinoma, while negativity with mCEA and KER AE1/AE3 is suggestive of hepatocellular differentiation.     

Sarcomatoid salivary duct carcinoma of the parotid gland

Salivary duct carcinoma (SDC) is a high-grade neoplasm known to histologically resemble high-grade ductal carcinoma in situ of the breast. We describe 3 cases of sarcomatoid salivary duct carcinoma, a heretofore unreported variant of SDC. Each case was a composite of SDC and sarcomatoid carcinoma and histologically similar to reported cases arising in the breast. The clinicopathologic features, including immunohistochemistry, of 3 cases were investigated. In the 3 men, ages 56, 68, and 70 years, the resected parotid tumors measured 1.5, 3.5, and 1.5 cm, respectively. Only the 3.5-cm tumor extended beyond the parotid gland into soft tissue. This patient died at 3 years with pulmonary metastases. The other patients were free of disease at 6 and 12 months. Histologically, each case was a composite of usual-type SDC and sarcomatoid carcinoma. SDC showed typical cribriform architecture, whereas anaplastic, spindled cells constituted the sarcomatoid areas. Immunohistochemically, epithelial elements stained as follows: cytokeratin (AE1/AE3 & CAM 5.2) positive in 3 of 3 cases, EMA positive in 3 of 3 cases, vimentin negative in 3 of 3 cases, desmin negative in 3 of 3 cases, c-erbB-2 positive in 1 of 2 cases. Sarcomatoid elements stained as follows: AE1/AE3 negative in 3 of 3 cases, CAM 5.2 rare positive cell in 1 of 3 cases, EMA focally positive in 3 of 3 cases, vimentin positive in 3 of 3 cases, desmin negative in 3 of 3 cases, c-erbB-2 negative in 2 of 2 cases. Electron microscopy, performed in one case, showed scattered junctional complexes congruent with epithelial differentiation. Immunohistochemical results, EMA and CAM 5.2 positivity, and ultrastructural findings supported our belief that these unique biphasic tumors represented SDC with sarcomatoid carcinoma. We conclude an element of sarcomatoid carcinoma rarely may arise in association with SDC, and it is erroneous to diagnose such tumors as "carcinosarcoma."     

Diagnosing tumours on routine surgical sections by immunohistochemistry: use of cytokeratin, common leucocyte, and other markers

Tumours of uncertain tissue of origin were investigated by immunohistochemistry on formalin fixed paraffin embedded sections. Two antibodies--PD7/26, an anti common leucocyte antigen, and CAM5.2, an anticytokeratin--recognised most lymphomas and carcinomas, respectively: 88% of these tumours were identified by the two antibodies alone. These antibodies permitted the separation of the cases into groups: positive with CAM5.2, positive with PD7/26, and a third comprising those negative with both. The negative group contained other tumours and a small number of carcinomas and lymphomas; many of the lymphomas were, apparently, of histiocytic origin. Comparison of CAM5.2 with other epithelial markers showed that it was the most effective. Some further classification of the tumours was carried out with a panel of organ and cell specific antibodies: mesotheliomas were recognised by their pattern of reactivity with epithelial markers. Overall, the tumour type was determined in 90% of cases. Immunohistochemistry performed as described can be a potent aid to the diagnostic histopathology of tumours.     

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.     

Ovarian small cell carcinoma. Histogenetic considerations based on immunohistochemical and other findings

Small cell carcinoma of the ovary is a rare, poorly understood aggressive tumor of young women, associated with paraendocrine hypercalcemia in two-thirds of the cases. Immunohistochemical staining of 15 small cell carcinomas, one-third of which were associated with hypercalcemia, 15 adult granulosa cell tumors, 15 juvenile granulosa cell tumors, and 5 Sertoli cell tumors, was performed with the use of antibodies against cytokeratins (AE-1/AE-3, CAM 5.2, 902), epithelial tumor-associated antigens (B72.3, epithelial membrane antigen [EMA]), vimentin, S-100, neuron-specific enolase (NSE), lysozyme, parathyroid hormone, and chromogranin-A in an attempt to define histogenetically this tumor type. One-third of the small cell carcinomas were positive for EMA, whereas all of them were negative for B72.3 and S-100. In contrast, one-third of the granulosa cell tumors were positive for S-100 and all of them were negative for EMA and B72.3. One of five Sertoli cell tumors were positive for EMA and two were positive for B72.3, but all were negative for S-100. Differences existed in the frequency, intensity, and/or pattern of staining for cytokeratin, vimentin, lysozyme, and NSE among the various tumor types. A single small cell carcinoma from a patient with hypercalcemia stained focally for parathyroid hormone, whereas all 30 granulosa cell tumors and 4 of 5 Sertoli cell tumors were nonreactive. Chromogranin-A staining was noted in four of five small cell carcinomas, none of ten granulosa cell tumors, and two of five Sertoli cell tumors. These immunohistochemical findings, as well as previous light and electron microscopic data, do not clearly indicate any specific cell as the cell of origin of the ovarian small cell carcinoma.     

E-cadherin nuclear staining is useful for the diagnosis of ovarian adult granulosa cell tumor

We recently have demonstrated nuclear localization of E-cadherin in ovarian adult granulosa cell tumors (Histopathology 2011;58:423). The purpose of the present study is to investigate the diagnostic utility of E-cadherin nuclear staining for the differential diagnosis between ovarian adult granulosa cell tumor and its morphological mimics. Tissue samples taken from 81 ovarian tumors and 20 extraovarian tumors were immunohistochemically stained using monoclonal anti-E-cadherin antibody recognizing cytoplasmic domain (clone 36 supplied by BD Biosciences, San Jose, CA). The ovarian tumors consisted of 30 adult granulosa cell tumors, 3 Sertoli-stromal cell tumors, 14 fibrothecomas, 5 carcinoid tumors, 1 large cell neuroendocrine carcinoma, 18 endometrioid adenocarcinomas, and 10 poorly differentiated serous adenocarcinomas. Extraovarian tumors consisted of 16 uterine endometrial stromal neoplasms and 4 pulmonary small cell carcinomas. Only tumor cells with nuclear staining were considered positive in this study. Ninety percent of adult granulosa cell tumors, 67% of Sertoli-stromal cell tumors, 64% of fibrothecomas, 75% of endometrial stromal neoplasms, 75% of small cell carcinomas, and the one large cell neuroendocrine carcinoma showed E-cadherin nuclear expression, whereas all the ovarian carcinoid tumors, endometrioid adenocarcinomas, and poorly differentiated serous adenocarcinomas were negative. E-cadherin nuclear staining is useful in distinguishing between adult granulosa cell tumors and ovarian adenocarcinomas or carcinoid tumors. However, it is of limited use for distinguishing between adult granulosa cell tumors and endometrial stromal neoplasms or small cell carcinomas. E-cadherin should be included in the immunohistochemical panel for an accurate diagnosis of ovarian adult granulosa cell tumors.