Distinction of endometrial stromal sarcomas from 'hemangiopericytomatous' tumors using a panel of immunohistochemical stains.

Endometrial stromal sarcomas are low-grade malignant tumors that may pose a diagnostic challenge, especially when they are present in an extrauterine site. Owing to the presence of an arborizing vasculature and cells with an undifferentiated appearance, endometrial stromal sarcomas can be confused with several soft-tissue neoplasms. We studied 17 endometrial stromal sarcomas, eight hemangiopericytomas, 14 solitary fibrous tumors, and 16 synovial sarcomas immunohistochemically, detecting the following antigens: CD10, estrogen receptor, progesterone receptor, bcl-2, CD34, smooth muscle antigen, epithelial membrane antigen and cytokeratin (AE1/AE3). Most endometrial stromal sarcomas stained positively for CD10 (16/17), estrogen receptor (17/17), progesterone receptor (15/17), and bcl-2 (17/17). Staining with antismooth muscle antigen was seen in 11 of 17 cases of endometrial stromal sarcoma, with more intense staining seen in areas showing smooth muscle differentiation. Staining with AE1/3 was seen in four of 17 endometrial stromal sarcomas, with two of the positive cases containing epithelioid cells. None of the endometrial stromal sarcomas expressed epithelial membrane antigen or CD34. More than half of the hemangiopericytomas (4/8) and solitary fibrous tumors (9/14) cases demonstrated CD10 expression either focally or in a patchy cytoplasmic and membranous pattern. Hemangiopericytomas, solitary fibrous tumors, and synovial sarcomas did not express estrogen receptor. Four of eight hemangiopericytomas and seven of 14 solitary fibrous tumors also showed patchy progesterone receptor expression. CD34 expression was identified in six of eight hemangiopericytomas and 13 of 14 solitary fibrous tumors, but we did not find expression of CD34 in synovial sarcoma. Differences between endometrial stromal sarcoma and other soft-tissue tumors were detected for all of the immunohistochemical markers (P<0.05), except anti-bcl-2 and AE1/3. Antibodies against CD10 mark a substantial number of hemangiopericytomas and solitary fibrous tumors (albeit not diffusely) and should always be combined with antiestrogen receptor and CD34 when the differential diagnosis includes endometrial stromal sarcoma. Unlike estrogen receptor antibodies, progesterone receptor antibodies show at least focal nuclear staining in most hemangiopericytomas, solitary fibrous tumors and rare synovial sarcomas, and are not useful for this differential diagnosis. All endometrial stromal sarcomas expressed bcl-2, mostly in a diffuse pattern, but this did not distinguish between endometrial stromal sarcoma and mimics. We therefore recommend the use of a small antibody panel comprising anti-CD10, anti-estrogen receptor, and anti-CD34 to distinguish endometrial stromal sarcomas from tumors with a predominant hemangiopericytomatous growth pattern.     

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.     

Diagnosis of necrotic and degenerate thyroid lesions: value of immunohistochemistry

Aims: Classification of necrotic or degenerate thyroid nodules can be difficult. The aim of this study was to investigate the value of cytokeratins, thyroid-specific markers (TTF-1 and thyroglobulin) and HBME-1 antibodies in such thyroid lesions. METHODS AND RESULTS: Twenty-eight necrotic or degenerate thyroid lesions, including four cervical cystic papillary carcinoma (CPC) metastases, were evaluated with immunohistochemistry for TTF-1, thyroglobulin, HBME-1, AE1&3, Cam5.2, MNF116 and cytokeratin (CK)19. There was loss of TTF-1 staining in all necrotic lesions, with positive staining in degenerate tumour cells of all four metastatic CPCs. Thyroglobulin was retained in 18 lesions. Dual CK19 and HBME-1 expression was seen only in six of seven necrotic papillary thyroid carcinomas and the four metastatic CPCs. Retained immunoreactivity for AE1&3 and Cam5.2 was seen in most necrotic papillary carcinomas (n = 11/11 and n = 10/11, respectively), poorly differentiated carcinomas (n = 2/3 and n = 3/3, respectively) and follicular-patterned areas of anaplastic carcinoma (n = 3/5 and n = 4/5, respectively). Cam5.2 showed spurious staining of macrophages in eight lesions. CONCLUSIONS: Thyroglobulin is useful in establishing the thyroid origin of a necrotic lesion. TTF-1 may be useful for highlighting degenerate tumour cells within metastatic CPCs. Retained expression of CK19 and HBME-1 is seen in necrotic papillary carcinomas. AE1&3 is the most specific and Cam5.2 the most sensitive of the CK cocktails in non-viable thyroid lesions.     

Usefulness of cytokeratin subsets for distinguishing monophasic synovial sarcoma from malignant peripheral nerve sheath tumor.

Monophasic synovial sarcoma (MSS) and malignant peripheral nerve sheath tumor (MPNST) are spindle cell sarcomas with overlapping histologic features, and their immunophenotypes may overlap, since MPNSTs express S-100 protein in only 50% to 60% of cases and rarely express epithelial markers, whereas MSSs can express S-100 protein in up to 40% of cases. We immunostained 29 cases of MSS and 29 cases of MPNST with antibodies to AE1/AE3, CAM 5.2, epithelial membrane antigen (EMA), S-100 protein, and cytokeratin subsets 7 and 19. Inclusion criteria for MSS included a consistent histology with expression of at least 1 epithelial marker. Inclusion criteria for MPNST included a tumor with a consistent histology arising in a patient with neurofibromatosis type 1 and/or in a plexiform neurofibroma, or ultrastructural confirmation of clear-cut schwannian differentiation. By definition, all cases of MSS were positive for at least 1 epithelial marker. Ten cases showed focal S-100 protein immunoreactivity, and 26 cases stained for cytokeratins 7 and 19. Twenty-three cases stained for both antigens, whereas only 2 cases were negative for both cytokeratins. Twenty-two MPNSTs demonstrated immunoreactivity for S-100 protein, and 11 stained focally for AE1/AE3 or EMA. Two cases of MPNST stained for cytokeratin 7, and only 1 case stained for cytokeratin 19. No cases of MPNST stained for both cytokeratins. Antibodies to cytokeratins 7 and 19 are useful adjuncts for the separation of MSS from MPNST. The majority of MSSs stain for one or both of these antigens, whereas most MPNSTs, including those that are EMA- or AE1/AE3-positive, do not express these cytokeratin subsets.     

Expression of CD10 in malignant müllerian mixed tumors and adenosarcomas: an immunohistochemical study.

CD10 has been demonstrated to be positive in endometrial stromal sarcoma (ESS) and thus is useful in establishing the diagnosis, but its expression in malignant müllerian mixed tumor (MMMT) and müllerian adenosarcoma remains to be clarified. In this study, 12 cases of MMMT (9 uterine, 2 tubal, and 1 metastatic), 6 cases of müllerian adenosarcoma (three corporeal, two cervical, and one tubal), and 7 cases of primary uterine sarcomas had their tissues examined immunohistochemically for expression of CD10, desmin, myoglobin, alpha-smooth muscle actin (SMA), and cytokeratin. Of the primary uterine sarcomas, two were primary rhabdomyosarcomas (one cervical and one corporeal), two were ESSs, two were high-grade leiomyosarcomas, and one was a high-grade endometrial sarcoma. Sarcomatous components in all cases of MMMT and müllerian adenosarcoma, as well as all uterine sarcomas, were positive for CD10, showing moderate to marked staining intensity with varying distribution except in one MMMT, which showed weak and very focal staining. In four MMMTs, three adenosarcomas, and one rhabdomyosarcoma, myoglobin- and/or desmin-positive rhabdomyoblastic cells were positive for CD10. The immunoreactivity for CD10 showed the same distribution for alpha-SMA and myoglobin in three and two MMMTs, respectively. In five cases of MMMT, carcinomatous components were focally positive for CD10, and in two cases small populations of round or short spindle cells in sarcomatous components were positive for CD10, alpha-SMA, and cytokeratin (CAM5.2). These results indicate that CD10 expression is not restricted to ESS but can be positive in MMMT and müllerian adenosarcoma as well as in a variety of uterine tumors including high-grade leiomyosarcoma and rhabdomyosarcoma. CD10 expression might be one of the characteristics of müllerian system-derived neoplastic mesenchymal cells.     

Myogenous phenotype of epithelial-like areas in endometrial stromal sarcomas

Approximately 25% of low-grade endometrial stromal sarcomas of the uterus contain areas of epithelial-like differentiation, which are often reminiscent of ovarian sex-cord tumors. It has been suggested that these areas may represent attempted differentiation toward either uterine glands or smooth muscle. To investigate these two possibilities, we examined the histologic and immunohistochemical features of 26 low-grade endometrial stromal sarcomas. Eight tumors had epithelial-like differentiation, which in some tumors was so prominent as to suggest a purely epithelial neoplasm. Areas typical of endometrial stromal sarcoma were vimentin positive, whereas epithelial-like differentiation expressed vimentin and the muscle markers muscle-specific actin and desmin, as well as cytokeratin, but not the epithelial marker epithelial membrane antigen. Epithelial-like differentiation in low-grade endometrial stromal sarcoma is not uncommon and, based on our immunohistochemical results after comparison with normal controls, epithelial-like differentiation has a myogenous rather than an epithelial phenotype.     

Pseudomyogenic (epithelioid sarcoma-like) hemangioendothelioma of bone: Clinicopathologic features of 5 cases

Pseudomyogenic hemangioendothelioma (PHE) is an uncommon mesenchymal tumor of intermediate malignant potential with characteristic clinicopathologic and genetic features. Although bone involvement accompanies nearly one-fourth of reported cases of soft tissue PHEs, primary intraosseous PHE is rare. Herein, we report five cases of primary intraosseous PHEs. Male to female ratio was 4:1, with an average age of 28 years (age range, 5–44 years). Radiologically, tumors presented as lytic lesions in the proximal femur (two), diaphysis of the tibia (one), distal radius (one) and vertebrae (one). Multifocal lesions were observed in four cases. Histopathologic examination revealed plump spindle cells and prominent nucleoli. New bone formation was noted in three cases. Immunohistochemically, all tumors were positive for CD31 and negative for CD34. Pan Cytokeratin (CK) (AE1/3) was positively expressed in all, except a single tumor, in which CK7 and Cam5.2 were expressed. INI1/SMARCB1 was completely retained in all tumors. A single patient underwent surgical resection. During follow-up, two cases showed no evidence of disease within two and five years, respectively. Differential diagnosis of a PHE of bone includes osteoblastoma, epithelioid angiosarcoma, metastatic carcinoma, metastatic rhabdomyosarcoma, and epithelioid sarcoma. Caution must be exercised as pan CK (AE1/3) might not be expressed; therefore, the use of other cytokeratins, such as Cam5.2 is recommended. Awareness of such an entity in bone is the key to the diagnosis.     

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.     

Anti-mesothelial markers in sarcomatoid mesothelioma and other spindle cell neoplasms

AIMS: To undertake a comparative evaluation of three antimesothelial markers (thrombomodulin, cytokeratin 5/6 and calretinin) with broad spectrum cytokeratin (AE1/AE3) in differentiating between sarcomatoid mesothelioma and a spectrum of spindle cell neoplasms. METHODS AND RESULTS: Thirty-one malignant sarcomatoid mesotheliomas were studied. Calretinin expression was focally identified in 12 (39%) tumours and thrombomodulin and cytokeratin 5/6 immunoreactivity was seen in nine (29%) cases. In comparison there was strong diffuse cytoplasmic reactivity with the broad spectrum cytokeratin (AE1/AE3) in 24 of 31 (77%) tumours. Thirty mixed spindle cells neoplasms were studied. No calretinin expression was identified in any case. Thrombomodulin immunoreactivity was identified in four (16%) cases (two angiosarcomas, two high-grade sarcomas, not otherwise specified). Cytokeratin 5/6 expression was seen in one high-grade pulmonary sarcoma originally termed malignant fibrous histiocytoma. None of the antimesothelial markers was expressed in the four spindle cell carcinomas studied. In contrast, broad spectrum cytokeratin was diffusely expressed in all four spindle cell carcinomas (three pulmonary, one renal), both synovial sarcomas, both malignant mixed Müllerian tumours, one of three pulmonary leiomyosarcomas and two of nine sarcomas, not otherwise specified. CONCLUSIONS: Immunohistochemistry has a more limited role in the diagnosis and distinction of sarcomatoid mesothelioma from other spindle cell neoplasms. The combination of a broad spectrum cytokeratin with calretinin combines both high sensitivity (77% for AE1/AE3) with high specificity (100% for calretinin) for sarcomatoid mesothelioma and can be diagnostically useful. The mesothelial markers, thrombomodulin and cytokeratin 5/6, are not useful alone in the diagnosis of sarcomatoid mesothelioma as each shows insufficient antibody sensitivity, although together they complement calretinin.     

Myxoid mixed low-grade endometrial stromal sarcoma and smooth muscle tumor of the uterus. Case report

We report the case of a 73-year-old female with myxoid mixed low-grade endometrial stromal sarcoma and smooth muscle tumor of the uterus. Grossly, the tumor sized 130 x 130 x 100 mm involved the uterine corpus almost in its entirety. Histologically, the tumor consisted of two cell types. In some areas, the tumor cells showed typical features of endometrial stromal tumors and resembled stromal cells of proliferative endometrium. In other areas, however, the tumor showed smooth muscle features and consisted of larger mostly epitheloid cells with a moderate amount of cytoplasm. In all areas, myxoid changes and multiple hyalinizing giant rosettes were present. The tumor infiltrated the myometrium in a pattern typical of low-grade endometrial stromal sarcoma. Immunohistochemically, the tumor cells showed expression of vimentin, estrogen and progesterone receptors and variable expression of CD10, α-smooth muscle actin, desmin, h-caldesmon, and cytokeratin AE1/AE3. Other markers examined including CD99, α-inhibin, cytokeratin CAM5.2, S-100 protein, and HMB45 were negative. To the best of our knowledge, mixed low-grade endometrial stromal and smooth muscle tumor with myxoid changes has not been described to date.     

Keratin expression in schwannoma; a study of 115 retroperitoneal and 22 peripheral schwannomas.

Schwannomas have been variably observed to be glial fibrillary acid protein (GFAP) and occasionally keratin positive, with antibodies reacting with multiple keratins (pankeratins, keratin cocktail (CK), but specific keratin polypeptides (K) have not been examined for in schwannoma. Since we observed CK positivity in retroperitoneal schwannomas, we wanted to study a large group of retroperitoneal and peripheral schwannomas with GFAP, CK and Ks to explore the frequency and biologic background of this finding. We immunohistochemically evaluated a large number of retroperitoneal (n=115) and peripheral schwannomas (n=22) for GFAP, 16 individual K and AE1/AE3 keratin cocktail. The great majority (104/115, 90%) of retroperitoneal schwannomas were positive for GFAP, and 72/104 (69%) cases were positive for AE1/AE3, often extensively. Both markers highlighted the cellular Antoni A areas, particularly adjacent to the capsule, myxoid or degenerative areas, and perivascularly. Most cases 87/104 (84%) stained for both AE1/AE3 and GFAP at least focally. No tumors stained for keratins that were GFAP negative. None of the immunostains for individual K showed positivity comparable to that obtained with AE1/AE3 CK. However, 62% were focally positive for high molecular weight K1 and 8/61 (13%) for K7. None of the retroperitoneal schwannomas were positive for other keratins including K2, 4, 5, 8, 9, 10 and K14-20. Peripheral schwannomas showed GFAP-positivity in only three of 22 cases (14%), and all were negative for keratins, both cocktail and individual K. We conclude that crossreactivity of AE1/AE3 with other intermediate filament proteins, such as GFAP, as previously observed in brain and glioma tissue, probably accounts for the extensive keratin-positivity seen in some retroperitoneal schwannomas. However, focal expression of K1 and K7 cannot be ruled out. Keratin-positive schwannomas should not be confused with other keratin-positive tumors, such as sarcomatoid carcinoma, mesothelioma, and synovial sarcoma.     

Atypical polypoid adenomyoma of the uterus: an immunohistochemical study on 5 cases

Immunohistochemical studies of atypical polypoid adenomyoma (APA) of the uterus are very rare. Five cases of APA were retrieved from the surgical cases of our laboratory. The ages were 38, 41, 54, 65, and 77 years (mean ± SD, 55 ± 14.6 years). The diameters of APA were 1.2, 1.9, 2.3, 3.2, and 7.0 cm (mean ± SD, 3.12 ± 2.00 cm). Histologically, APA consisted of complex glandular element and mesenchymal fibromuscular element. No endometrial stroma was present. Mucins were found in the glands but not in the mesenchyma. The glands were consistently positive for pancytokeratin (AE1/3, CAM5.2), cytokeratin (CK) 7, CK8, CK18, CK19, vimentin, CA125, estrogen receptor, progesterone receptor, MUC1, and MUC6. The glands were consistently negative for CK14, CK20, CEA, epithelial membrane antigen, S100 protein, p53, CD10, MUC2, and MUC5AC. Some cases were positive for CK34βE12 (4/5), CK5/6 (4/5), and CA19-9 (4/5). The Ki-67 labeling ranged from 3% to 10%. The mesenchymal element was consistently positive for vimentin, α-smooth muscle actin, estrogen receptor, progesterone receptor, and CD10, while consistently negative for pancytokeratin (AE1/3, CAM5.2), CK34βE12, CK5/6, CK7, CK8, CK14, CK18, CK19, CK20, CEA, epithelial membrane antigen, S100 protein, CA125, CA19-9, p53, MUC1, MUC2, MUC5AC, and MUC6. Some cases were positive for desmin (2/5). Ki-67 labeling ranged from 1% to 8%. In conclusion, the immunoprofile of APA was reported. The findings provide basic knowledge of APA of the uterus.     

The cytokeratin profile of medullary carcinoma of the breast

AIMS: The cytokeratin (CK) phenotype and vimentin expression of 31 medullary carcinomas was studied using commercially available antibodies on archived material. Comparing the phenotype of typical and atypical tumours and the phenotype of metastases, the biological significance of cytokeratin and vimentin expression in medullary carcinomas of the breast was determined. METHODS AND RESULTS: Antibodies to CK4, CK5 and 6, CK7, CK14, CK8 and 18, CK19, CK20 and to vimentin were used. All the typical and atypical medullary carcinomas and the metastases (10 cases) stained negatively for CK4 and positively for CK8-18 (CAM5.2). Almost all the tumours were CK7 and CK19 positive and CK20 negative. Twelve per cent of the tumours contained CK14. Twenty-five per cent of the typical, 43% of the atypical and 20% of the metastatic medullary carcinomas showed CK5-6 positivity. No association between the cytokeratin-vimentin profile of the tumours and axillary node metastases, tumour size or oestrogen receptor status was found but instability of CK expression was demonstrated by comparing the primary tumours with their metastases. CONCLUSIONS: : Medullary carcinomas of the breast express all the glandular type CKs including CK19 and additionally a proportion of the tumours expresses some of the CKs typical for myoepithelial cells. There was no correlation with prognostic factors.     

Cytokeratin intermediate filament expression in benign and malignant breast disease.

AIM--To carry out a comprehensive study of cytokeratin expression in benign and malignant breast epithelium and breast myoepithelial cells; to examine changes in the cytokeratin profile in malignant and benign epithelium and in carcinomas of increasing histological grade. METHODS--Frozen sections from fibroadenomas (19 cases), fibrocystic disease (19 cases), and infiltrating ductal (68 cases), lobular (seven cases), and mucinous carcinomas (three cases) were examined using a panel of monoclonal antibodies. RESULTS--The luminal epithelium in all fibroadenomas and all cases of fibrocystic disease, as well as tumour cells in most carcinomas, reacted with the specific antibodies to cytokeratins 7, 8, 18, and 19 and to antibodies which included these cytokeratins in their specificities (Cam 5.2, AE1, AE3, RCK102, and LP34). In a few ductal carcinomas none of the tumour cells reacted for cytokeratins 7, 8, or 18. Three ductal carcinomas expressed cytokeratin 14. Only occasional cases expressed cytokeratins 3, 4, 10, and 13. Antibodies which included cytokeratins 5 and 14 in their specificities detected myoepithelial cells less efficiently than antiactin antibodies. CONCLUSION--The cytokeratin profiles in the luminal epithelium in benign breast disease and in tumour cells in most carcinomas are similar in most cases. Some carcinomas, however, are negative for cytokeratins 7, 8, or 18. This may provide a means of predicting the biological behaviour of a histologically borderline lesion.     

Histogenesis of cardiac myxomas. An immunohistochemical study of 19 cases, including one with glandular structures, and review of the literature

To elucidate the histogenesis of cardiac myxomas, the literature has been reviewed, including all previous immunohistochemical studies, and an extensive immunohistochemical study of 19 cardiac myxomas has been undertaken with antibodies to factor VIII, desmin, vimentin, myoglobin, cytokeratin (CAM 5.2 and AE1/AE3), and S100 protein. In all cases, vimentin stained endothelial as well as "myxoma" (stromal) cells. In contrast, factor VIII only stained endothelial cells. In 16 cases, desmin stained cells in the vascular structures; in 5 cases, desmin stained myxoma cells. In 6 cases, S100 protein stained the myxoma cells strongly. Myoglobin was absent in all cases. In 1 case, CAM 5.2 and AE1/AE3 stained glandular structures. The results indicate the following: that most cardiac myxomas are true neoplasms derived from "embryonal rests"; that the various mesenchymal cells found in cardiac myxomas (myxoma cells, endothelial cells, smooth-muscle cells, fibroblasts, myofibroblasts, and chondroid cells), express differentiation, not histogenesis; that, apparently, only the myxoma cells are neoplastic; and that the glandular structures infrequently found in cardiac myxomas originate from entrapped foregut rests.     

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.     

TLE1 is expressed in the majority of primary pleuropulmonary synovial sarcomas

Pleuropulmonary synovial sarcoma (PPSS) is a rare entity, similar to synovial sarcoma of soft tissue (STSS). There are 120 published cases of PPSS, but no studies have explored the expression of TLE1. In soft tissues, it has been proven a useful marker, but in tumors of other sites, its expression has not been explored. The main objective was to study the expression and diagnostic sensitivity and specificity of TLE1 in a group of PPSS, of which the diagnosis was corroborated by fluorescence in situ hybridization confirming t(X;18) in a tissue microarray. Immunohistochemistry including TLE1, vimentin, CD99, CD56, bcl-2, AE1-AE3, EMA, CD34, CK7, CK19, calponin, and S-100 was performed on all PPSS and on 25 control cases (five carcinomas, ten mesotheliomas, and ten thoracic sarcomas). TLE1 was positive in 11 cases (73.3%); bcl-2 and vimentin in 100%; calponin and CD56 in 26.6%; CD99, CK AE1-AE3, CK19, CK7, and EMA in 80%; and S100 negative in all. The only biphasic PPSS was positive for epithelial markers only in the epithelial component. TLE1 was negative in all control cases. TLE1 is expressed in 73% of PPSS, a value inferior to that reported in STSS, but is highly specific for PPSS. TLE1 may therefore be of value in the differential diagnosis of PPSS, but should be used in a panel of antibodies.     

Expression of androgen receptors in benign and malignant endometrial stromal neoplasms

Several studies have shown that endometrial stromal neoplasms express estrogen and progesterone receptors (ER, PR). To our knowledge, the presence or absence of androgen receptors (AR) in these rare uterine neoplasms has not been investigated. Tumors (n=20)—3 endometrial stromal nodules, 14 low-grade endometrial stromal sarcomas (ESS, low grade), and 3 high-grade endometrial sarcomas (undifferentiated endometrial sarcoma, UES)—were studied. Immunohistochemical analyses for ER, PR, and AR were performed on formalin-fixed, paraffin-embedded archival material. Positive immunoreactions for ER and PR were observed in 14 (70%) and 17 (85%) cases, respectively. Furthermore, 9 cases (45%) were positive for AR. Among 17 ESS and UES cases, 7 (41%) revealed positivity for AR. Two of three benign stromal nodules were also positive for AR. Moreover, one of the three high-grade sarcomas (undifferentiated endometrial sarcoma) was negative for both ER and PR, but showed positive reaction for AR. In summary, ARs are expressed in 45% of endometrial stromal neoplasms. In addition to determination of ER and PR, the results of immunohistochemical examination of AR in these rare uterine tumors may have some impact on the postoperative management of the patients.     

宫内膜活检或刮出物中子宫内膜间质肉瘤的诊断

目的：探讨宫内膜活检或刮出物诊断子宫内膜间质肉瘤的标准和鉴别诊断注意事项。方法：对９例临床和病理资料完整并经宫内膜活检或刮出物中确诊的子宫内膜间质肉瘤,对照其随后进行的子宫切除标本的蜡块,再次常规制片,ＨＥ染色,光镜进行对比观察。结果：９例宫内膜活检或刮宫标本中,有６例分化良好,酷似子宫内膜增生过长时的间质细胞。有３例分化差者,其中２例酷似恶性淋巴瘤,１例酷似多形肉瘤。９例均见簇状分布的子宫内膜螺