Renal angiomyolipoma with predominant muscular epithelioid components. 2 cases

We report two cases of pararenal angiomyolipomas, in two middle-aged women without tuberous sclerosis. Both tumors were made of muscular epithelioid cells without atypia, some of which were stained by HMB-45 antibody. The fibrous stroma contained numerous thick-walled blood vessels but no adipose component. The ultrastructural examination revealed that muscular epithelioid cells contained myofilaments and melanosomas. Because of their immunohistochemical and ultrastructural profiles, both tumors may be included in the family of lesions composed of perivascular epithelioid cells (PEC). This tumor type is considered as a particular variant of angiomyolipoma with predominant muscular epithelioid component. The immunohistochemical expression of progesterone and estrogen receptors by both tumors may suggest their hormonodependent character.     

Renal angiomyolipomas--a study of 18 cases

Angiomyolipoma is a distinctive neoplasm composed of an intimate admixture of three components, viz. mature adipocytes, smooth muscle cells and blood vessels. This study was undertaken to better define the various morphological patterns of angiomyolipoma and their immunohistochemical profile. The paraffin blocks and slides of 18 cases of renal angiomyolipoma, accessioned over a period of 8 years from Tata Memorial Hospital, were reviewed. There were 2 men and 16 women in the age range of 17 to 68 years. Pre-operative fine needle aspiration cytology (FNAC) was performed in 6 cases, of which 5 were erroneously diagnosed as renal cell carcinomal sarcoma. Histologically, 14 cases revealed conventional histology. The remaining 4 cases were particularly misleading posing diagnostic problems due to variant patterns (leiomyomatous variant-3 cases and epithelioid variant- 1 case). Apart from the usual histology, necrosis, giant cells, and varying degrees of nuclear pleomorphism were present in three of the cases. Immunohistochemistry performed in 16 cases revealed immunoreactivity for HMB45 in all the 16 tumors (100%), estrogen receptor (ER) and progesterone receptor ((PR) in 2 cases (12.5%) and 6 cases (37.5%) respectively.     

Expression of steroid hormone receptors, their regulated proteins, and bcl-2 protein in myofibroblastoma of the breast

AIMS: To investigate the possible role of steroid hormones in the pathogenesis of myofibroblastoma (MFB) of the breast, we analysed the immunohistochemical expression of oestrogen, progesterone, androgen receptors, their regulated proteins and bcl-2 protein in a series of this rare tumour. METHODS AND RESULTS: Paraffin-embedded sections from seven cases of MFB of the breast (five male; two female) were immunohistochemically tested for the expression of oestrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), oestrogen-regulated pS2 protein, androgen-regulated prostate-specific antigen (PSA) and bcl-2 protein. Rare cases of benign spindle cell tumours or tumour-like lesions of the breast (primitive fibromatosis, inflammatory pseudotumour, muscular hamartoma) which enter into the differential diagnosis with MFB, were also investigated and compared with MFB. All cases of MFB showed a diffuse (70-90% of neoplastic cells) and strong nuclear labelling with ER and PR, whereas AR was expressed only in three cases (two men and one woman) in about 60-70% of cells. Conversely, no immunostaining was detected for the pS2 protein and PSA. bcl-2 protein immunoreactivity was found in all cases of MFB, although with a variable degree of expression. No expression for steroid hormone receptors, their regulated-proteins and bcl-2 protein was observed in the rare benign spindle cell lesions of the breast included in this study. CONCLUSION: The in-situ detection of ER, PR and AR suggests that steroid hormones and their receptors are implicated in the pathogenesis of breast MFB. The consistent demonstration of bcl-2 protein, associated with a positive ER/PR status, provides evidence that bcl-2 may be an oestrogen-regulated protein also in MFB and that probably plays a role in the tumorigenesis. Finally, we postulate that the ER/PR and bcl-2 positive immunoprofile of MFB of the breast, in contrast to the negative profile of other rare primitive benign spindle cell lesions of the breast herein studied, might be exploited as an ancillary diagnostic aid in differential diagnosis of doubtful cases.     

PEComas: the past,the present and the future

The perivascular epithelioid cell (PEC) is a cell type constantly present in a group of tumors called PEComas. PEC expresses myogenic and melanocytic markers, such as HMB45 and actin. Recently, recurrent chromosomal alterations have been demonstrated in PEC. At present, PEComa is a widely accepted entity. In the past 10 years, the use of this term has allowed to report and describe numerous cases permitting to start highlighting the biology of this group of lesions. PEComas are related to the genetic alterations of tuberous sclerosis complex (TSC), an autosomal dominant genetic disease due to losses of TSC1 (9q34) or TSC2 (16p13.3) genes which seem to have a role in the regulation of the Rheb/mTOR/p70S6K pathway. There are some open questions about PEComas regarding its histogenesis, the definition of epithelioid angiomyolipoma and the identification of the histological criteria of malignancy. An innovative therapeutic trial using rapamycin is under way for tumors occurring in TSC such as renal angiomyolipoma and lymphangioleiomyomatosis. Its success could provide the rationale for the use of the same drug in other lesions composed of PECs, especially in the malignant ones.     

Glutamine synthetase interpretation in hepatocellular adenoma

Lymphangioleiomyomatosis (LAM) of the lung is a rare low-grade malignancy affecting primarily women of childbearing age. LAM is characterized by the proliferation of SMA and HMB-45 positive spindle-shaped and epithelioid cells throughout the lung in the form of discrete lesions causing cystic destruction and ultimately respiratory insufficiency. LAM occurs sporadically or in patients with tuberous sclerosis complex (TSC) and is etiologically linked to mutations in the TSC1 and TSC2 genes. Although LAM cells are known to express estrogen and progesterone receptors (ER and PR, respectively), their respective expression level was never determined. Therefore, here we measured the immunohistochemical expression of ERs and PRs in a large series of pulmonary LAM cases using the Aperio Spectrum Analysis Platform. Our case series comprised open lung biopsy specimens from 20 LAM patients and lungs explanted during the course of lung transplant from 24 patients. All cases were positive for ER and PR. PR expression was statistically significantly higher than ER in 80 % of the biopsies while ER predominated only in one case. Specimens from explanted cases of LAM had relatively fewer PR-positive nuclei. As a result, PR expression was significantly higher than ER in 38 % of the cases, whereas ER predominated in 33 %. Overall, PR expression predominated in 57 % of cases and ER in 21 %. These data indicate that PR frequently prevails over ER in pulmonary LAM. LAM is unusual in its high PR/ER ratio; other female neoplasms show a definite prevalence of ER. Our findings therefore warrant further study of PR function in LAM.     

Value of estrogen and progesterone receptor immunostaining in distinguishing between peritoneal mesotheliomas and serous carcinomas

The differential diagnosis between peritoneal mesotheliomas and serous carcinomas involving the peritoneum may be difficult, but it can be facilitated by the use of immunohistochemistry. To determine whether estrogen receptors (ER) or progesterone receptors (PR) may have any value as immunohistochemical markers for discriminating between these malignancies, 40 serous carcinomas of the ovary metastatic to the peritoneum, 7 primary peritoneal serous carcinomas, 30 epithelioid peritoneal malignant mesotheliomas, 5 well-differentiated papillary mesotheliomas, and 4 adenomatoid tumors were immunostained for ER and PR. Reactivity for ER was obtained in 35 (88%) of the metastatic serous carcinomas of the ovary and 6 (86%) of the primary peritoneal serous carcinomas, whereas positivity for PR was observed in 24 (60%) of the metastatic serous carcinomas and 4 (56%) of the primary peritoneal serous carcinomas. None of the mesotheliomas or adenomatoid tumors expressed ER or PR. It is concluded that, because of its high sensitivity for serous carcinomas, ER immunostaining could be very useful in distinguishing between serous carcinomas and peritoneal mesotheliomas. Immunostaining for PR, however, has little practical utility.     

Uterine angiomyolipoma: case report and review of the literature

Extrarenal angiomyolipomas (AML) have been reported at various anatomical sites, but infrequently in the gynecological region. In the uterus, only a few cases have been described. We describe a uterine angiomyolipoma occurring in a 40-year-old woman without evidence of tuberous sclerosis. The tumor arose on the right wall of the uterine body and was partially cystic, and it was associated with marked degeneration. It was composed of mature adipose tissue, anomalous blood vessels and non-vascular smooth muscle cells. Immunohistochemistry revealed that non- vascular smooth muscle cells were positive for alpha-smooth muscle actin (alpha-SMA), desmin, vimentin, antihuman muscle actin (HHF35) and progesterone receptor (PR), and negative for cytokeratin, antihuman melanoma (HMB45), CD34, S-100 and estrogen receptor (ER). It is of particular interest that non-vascular smooth muscle cells were negative for HMB45, in contrast to renal and other extrarenal AML in which HMB45 immunoreactivity has been demonstrated in these cells.     

Down-regulation of bcl-2 expression is closely related to squamous differentiation and progesterone therapy in endometrial carcinomas

To clarify whether changes in bcl-2 protein (bcl-2) expression are directly linked to differentiation, an immunohistochemical investigation was carried out on areas of squamous differentiation within 38 endometrial carcinomas (25 grade 1 and 13 grade 2 cases) as well as eight grade 1 carcinomas after progesterone therapy. Such areas of altered differentiation were subdivided into foci of squamous metaplasia (Sq-M) and morules. Expression of oestrogen and progesterone receptors (ER and PR) and cell proliferation were also examined. Immunoreactivity scores for bcl-2 in Sq-M foci were significantly lower than in the surrounding tumour regions, in line with reduced staining for ER and PR and Ki-67 labelling indices (LIs), while morule values were intermediate. After progesterone therapy, a marked decrease in bcl-2 immunoreactivity was found in the response group, along with low Ki-67 LIs and tumour cell maturation. These results indicate that in endometrial carcinoma, down-regulation of bcl-2 expression may be closely linked with squamous differentiation, in line with changes in ER and PR expression, as well as in cell proliferation. In addition, bcl-2 expression appears to be down-regulated by progesterone therapy through tumour cell maturation, indicating that bcl-2 may be a clinically useful marker of hormone therapy effects. © 1997 John Wiley & Sons, Ltd.     

子宫腺肌症雌激素受体、孕激素受体与bcl-2的表达

目的 探讨雌激素受体（ER）、孕激素受体（PR）和bcl-2在子宫腺肌症中异位和在位内膜的表达及意义。方法 用免疫组化EnVision法检测40例子宫腺肌症在位子宫内膜和肌间异位内膜ER、PR和bcl-2的表达情况。结果 在位和异位子宫内膜组织中均有ER、PR和bcl-2的阳性表达。其中腺上皮阳性表达率高于间质（P〈0．05）,且异位内膜的腺上皮bcl-2阳性表达率高于在位组织（P〈0．05）;ER和PR的表达两者差异无显著性（P〉0．05）。异位内膜腺体ER、PR与bcl-2表达具有相关性（P〈0．01）。结论 子宫腺肌症异位和在位子宫内膜组织中均有ER、PR和bcl-2的阳性表达,可能与子宫腺肌症的发生、发展有关。     

Malignant PEComa of the adrenal gland

Perivascular epithelioid cell neoplasms, also known as PEComas, are unique mesenchymal tumors exhibiting perivascular epithelioid cell differentiation, characterized by a mixed myogenic and melanocytic phenotype. PEComas arising in visceral organs outside of the kidney, liver, and lung are rare, and often pose problems in diagnosis. Examples of this neoplasm originating in the adrenal gland are limited. The present report details the clinical and pathologic features of an unusual case of a pure epithelioid PEComa (epithelioid angiomyolipoma) of the adrenal gland exhibiting clinically malignant behavior in the form of pulmonary metastases, a feature not previously described in tumors of this site. The diagnosis was supported by immunohistochemical studies demonstrating expression of myoid and melanocytic antigens. The present case serves to emphasize the potential of PEComa for clinically aggressive behavior and the importance of distinguishing this tumor from other epithelioid neoplasms that are more commonly encountered in the adrenal gland.     

Aspiration cytology, histology and hormone status in solid and cystic papillary tumor of pancreas--report of three cases

Solid and cystic papillary tumor of pancreas (SCPT) are rare tumors. Of the well described cases 95% have occurred in women of reproductive age, suggesting a role of hormonal factors in the pathogenesis of this tumor. Only few studies evaluating estrogen and progesterone receptor status have found it to be positive. Cytohistocorrelation and immunohistochemistry for estrogen (ER) and progesterone (PR) receptors of three such cases are reported here. All three were diagnosed by fine needle aspiration cytology (FNAC) and showed cytoplasmic positivity for ER and PR receptors. May-Grunwald Giemsa, Papanicolaou and hematoxylin and eosin stained slides were evaluated for cytology and histopathology. Unstained methanol fixed slides were used for immunohistochemistry. The cytoplasmic staining of ER and PR receptors cannot be underestimated, as shown by Carbone A et al which represents ERII receptors. This study confirms the presence of ER and PR receptors in these tumors and highlights the already established cytological features.     

Renal angiomyolipoma with epithelial cysts: a rare entity and review of literature

Renal angiomyolipoma (AML) with epithelial cysts (AMLEC) is a comparatively rare benign renal tumor that is recently recognized as a distinct entity and there are relatively few reported cases in the English-language literature. To date 19 cases of AMLEC have been reported in 2 case series and a few case reports. AMLEC has been described as a cystic variant of AML. Herein we reported an AMLEC in a 25-year-old female patient, and to the best of our knowledge this is the first case report of AMLEC in Chinese. She was incidentally found to have a kidney-occupying lesion during a routine medical examination for 1 month. CT examination demonstrated a multilocular cystic lesions arising from right-kidney lower pole. The patient underwent the partial nephrectomy. Histological examination of the tumor was composed of epithelial cysts, compact subepithelial mullerian-like stroma and muscle-predominant AML. Immunohistochemically, epithelial cysts were positive for CK but negative for ER, PR, CD10 and HMB-45; the subepithelial stroma and muscle-predominant AML were positive for ER, PR and HMB-45; the subepithelial stroma was negative for SMA, but muscle-predominant AML was positive for SMA. The final histopathological diagnosis was AMLEC.     

90例乳腺良性病变组织中ER和PR的表达

应用免疫组化方法对９０例良性乳腺病变组织进行ＥＲ、ＰＲ的检测。结果，ＥＲ阳性率为８４．４％，ＰＲ为８３．３％，与同期乳腺癌的ＥＲ和ＰＲ阳性率比较有非常显著性意义，ＥＲ阳性以纤维腺瘤，导管内乳头状瘤，囊性乳腺增生症最为常见，小叶内增生ＥＲ阳性相对减少，同时对乳腺组织间质存在前背景染色问题加以讨论。     

Hepatic epithelioid angiomyolipoma with an unusual pathologic appearance: expanding the morphologic spectrum

Hepatic epithelioid angiomyolipoma (AML) is a rare lesion that is characteristically composed of a predominant or exclusive population of epithelioid cells coexpressing melanocytic and myogenic markers. The cystic variant of epithelioid AML is exceedingly uncommon. In this study, we present the clinicopathological features of a case of hepatic epithelioid AML with remarkable cystic degeneration in a 34-year-old female as well as with a literature review. A magnetic resonance imaging scan revealed a well-defined 30 cm × 25 cm hepatic mass. Sectioning of the well-defined mass revealed a non-encapsulated tumor that was multiloculated with amorphous necrotic tissue and hemorrhagic fluid. The inner cystic wall was rough and brownish-black in color. Microscopically, the tumor largely consisted of epithelioid cells that comprised approximately 95% of the total neoplastic components but also contained some spindle myoid cells, mature fat, and a thick-walled vasculature. Both intracellular and extracellular hyaline globules were frequently identified. Necrosis and invasive growth patterns were also present. By immunohistochemistry, spindle-epithelioid neoplastic cells were variably positive for Melan-A, HMB45, and SMA but were uniformly negative for epithelial and hepatocytic markers. This is the third report of a cystic AML in liver. The patient was followed for 71 months without any evidence of metastasis or recurrence.     

Endometrial carcinoma: association of steroid hormone receptor expression with low angiogenesis and bcl-2 expression

In endometrial tissues, malignant change may be accompanied by a loss of hormone dependence which is, usually, reflected in a parallel loss of oestrogen and progesterone receptors (ER and PR). In this study, the steroid receptor status of 164 endometrial carcinomas was related to intratumoural angiogenesis and the apoptotic proteins bcl-2 and p53. Relationships to conventional histopathological features and patient survival were also sought. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissues. The mean follow-up was 55 months (range 19-167 months). Specific nuclear staining for ER and PR was detected in 35% and 32% of endometrial carcinomas, respectively, and was very commonly co-expressed (P<0.0001). The failure of demonstrating a steroid receptor complement in endometrial neoplasms was, in general terms, an adverse prognostic sign. Thus, ER or PR loss was significantly associated with non-endometrioid carcinomas (ER P=0.01; PR P=0.004) and with deep myometrial invasion (ER P<0.0002), high intratumoural angiogenesis (PR P<0.01) and the absence of bcl-2 expression (PR P<0.005). There was a trend for patients with ER or simultaneous ER/PR expression to have an improved survival, but this association did not reach the level of statistical significance. In multivariate analysis (all stages), tumour cell type (endometrioid versus non-endometrioid carcinomas) and stage of disease were the only variables associated with prognosis (P=0.01 and P<0.0001, respectively), with tumour cell type retaining its independent prognostic value and within stage-I endometrial carcinomas (P=0.02). It is suggested that the loss of steroid hormone receptors in endometrial carcinomas is associated with a more aggressive phenotype and the switching-on of angiogenic pathways.     

Immunohistochemical analysis of estrogen receptor alpha, estrogen receptor beta and progesterone receptor in normal human endometrium

The endometrium expresses estrogen (ER) and progesterone receptors (PR), which are involved in autocrine and paracrine regulation processes in response to estrogen and progesterone. The aim of the present study was to evaluate immunohistochemical distribution patterns of estrogen receptor alpha (ER alpha), estrogen receptor beta (ER beta) and PR in normal human endometrial tissue with the use of monoclonal antibodies. Human endometria were obtained from 17 premenopausal patients undergoing surgery for non-malignant diseases and were classified to be in proliferative, early secretory and late secretory phases by histological and anamnestical means. Distribution patterns of the steroid receptors were evaluated using the IRS-score and the Mann-Whitney rank-sum test was used to compare the means. Correlation was assessed with the Spearman factor and linear regression analysis. ER alpha and PR expression decreased significantly (p<0.05) in glandular epithelium from the proliferative to the late secretory phase. ER beta expression showed a similar significant decrease (p<0.05), although staining intensity was lower than that of ER alpha. A significant correlation between expression of all three steroid receptors was observed (p<0.001). Distribution patterns of ER alpha, ER beta and PR in normal human endometrium showed a cyclic variation during the menstrual cycle. A significant correlation between expression of ER alpha, ER beta and PR was also demonstrated using regression analysis, indicating dependence of expression of these three steroid receptors. The present study shows the presence of steroid receptors in human endometrial epithelium, indicating that these cells respond to estrogen and progesterone and thus playing a significant role in endometrial physiology.     

Presence of cytoplasmic progesterone receptors in hepatic adenomas. A report of two cases

Two cases of hepatic adenomas observed in young women with (Case 1) or without (Case 2) prior history of oral contraceptive use are investigated for the presence of cytoplasmic estrogen receptors (ER) and progesterone receptors (PR) by dextran-coated charcoal method. Such a study reveals the presence of PR and the absence of ER in adenomatous tissue from both the cases, while both ER and PR are detected in the normal liver adjacent to adenoma. The significance of these findings is discussed, and the presence of PR is interpreted as a biologic response to estrogens, even in the apparent absence of ER.     

Immunohistochemical profile of endometrial adenocarcinoma: a study of 61 cases and review of the literature.

The differences in immunohistochemical expression of p53, bcl-2, bax, estrogen receptor (ER), and progesterone receptor (PR) were evaluated in 40 endometrioid and 21 papillary serous carcinomas of endometrium and correlated with known predictors of survival, such as grade and stage. Uterine papillary serous adenocarcinomas (UPSA) showed significantly higher p53 expression than did uterine endometrioid adenocarcinomas (UEA) (76.2% versus 35%), whereas both ER and PR were more often positive in endometrioid than in serous tumors (p = .005 and .0005). No significant difference was found in bcl-2 and bax expression between both histologic types. However, there was definite decrease in intensity of bcl-2 in UPSA compared with UEA. In endometrioid carcinoma, p53 overexpression was associated with high-grade and advanced-stage tumors (p = .0006 and .006), whereas ER and PR expression was associated with low-grade and early-stage tumors (p = .0006 and .0001; p = .003 and .0006). Bcl-2 immunopositivity was more common in low-grade, early-stage rather than in high-grade, advanced-stage adenocarcinomas, but the difference was not statistically significant (p = .24 and .07). Bax immunopositivity was associated with well-differentiated (p = .04) and early-stage tumors. Furthermore, a significant inverse relationship between bax and p53 reactivity was defined (p = .05), especially in tumors of endometrioid type. Bax and PR immunoexpression correlated near the limit of statistical significance (p = .08), whereas no relationship was found among bax, bcl-2, and ER immunopositivity. Our results indicate that the differences in immunohistochemical profiles of endometrioid and serous carcinomas support the existence of different molecular pathways of their development. The correlation of immunohistochemical findings with histologic grade and clinical stage could help in predicting biologic behavior and planning treatment in patients who are diagnosed as having these tumors.     

肾脏上皮样血管平滑肌脂肪瘤的病理观察

目的对肾脏上皮样血管平滑肌脂肪瘤（epithelioid agiomyolipoma,EAML）的病理诊断、鉴别诊断和预后进行分析。方法2例肾脏EAML（其中1例为复发病例）,复习其临床资料,病理学检查包括常规病理学、免疫组织化学和超微结构,并进行随访。结果光镜下肿瘤均主要由具有多形性和不典型性的上皮样细胞组成,部分区域有明显的血管周上皮样排列;可见出血和坏死;并可见静脉内瘤栓;淋巴结内可见上皮样肿瘤细胞累及。免疫组织化学肿瘤细胞（包括淋巴结内肿瘤）HMB45、平滑肌肌动蛋白（SMA）、神经元特异性烯醇化酶（NSE）和波形蛋白弥漫阳性;S-100、melanpan和CD68散在阳性;而上皮细胞膜抗原（EMA）、AE1／AE3、CK7、CD117、肌肉特异性肌动蛋白（MSA）、结蛋白、白细胞共同抗原（LCA）、CD20、CIM5RO、CD30、CD15、嗜铬素（CgA）、突触素（Syn）、bcl-2、雌孕激素受体（ER、PR）和p53均为阴性。电镜检查可见一些肿瘤细胞内有黑色素小体样的致密颗粒、肌丝、密体,肿瘤细胞外可见不连续的基膜。2例患者手术后10个月状态良好,无肿瘤局部复发和转移征象。结论血管周上皮样排列、寻找经典血管平滑肌脂肪瘤的结构和肿瘤细胞表达HMIM5和SMA对于诊断和鉴别诊断至关重要。而细胞的不典型性、出血坏死和核分裂象可能只表明肿瘤的恶性潜能：淋巴结受累、肾静脉瘤栓不是恶性的诊断依据：只有远处转移才是恶性的证据。     

Cytometrical image analysis for immunohistochemical hormone receptor status in breast carcinomas

A cytometrical image analyzing method for nuclear protein was established using WinROOF, a commercially available, inexpensive software, to determine the status of both estrogen and progesterone receptors. Immunohistochemical evaluation of estrogen receptors (ER) and progesterone receptors (PR) was performed with the anti-ER (clone 1D5) and the anti-PR (clone PgR636), respectively, combined with dextran polymer reagent EnVision+, all of which are approved in vitro diagnostics in Japan. The immunostained results were captured as digital images in Windows, and then analyzed in WinROOF with macroinstructions for analyzing each captured area either immunolabeled with chromogen or counterstained with hematoxylin. This image analysis method graded the immunostained nuclei of carcinoma cells based on staining intensities, and calculated the labeling index (LI) for both ER and PR. Furthermore, the LI correlated highly with the results from a histology score (HSCORE) when 20 breast carcinomas were quantified. Regarding ER, when 20% in the LI was considered as the cut-off point for positive, the positivity of ER in computer-assisted analysis was 75% (15 of 20 cases), and was completely concordant with that of HSCORE-based analysis. These results indicate that the cytometrical image analysis-based quantification could be appropriately applied to the objective determination of the immunohistochemical status of both ER and PR.