Pseudoangiomatous stromal hyperplasia (PASH) of the breast with foci of morphologic malignancy: a case of PASH with malignant transformation?

Pseudoangiomatous stromal hyperplasia (PASH) is a benign proliferation of the hormonally responsive, specialized mammary stroma characterized by slit-like pseudovascular spaces lined by bland spindle cells. It is usually an incidental microscopic finding but in some cases it may present as a slowly growing mass. A malignant counterpart for this lesion has not been reported. We describe a case of PASH with foci of malignant histologic features presenting as a slowly growing mass in a 30-year-old woman. The previously reported variants of PASH and the other mammary stromal lesions related to PASH are also discussed. This is perhaps the first case of PASH with foci of malignant histologic features reported in the literature and represents a rare sarcoma derived from specialized hormonally responsive mammary stroma.     

Aggressive angiomyxoma of male genital region. Report of 4 cases with immunohistochemical evaluation including hormone receptor status

Aggressive angiomyxoma (AA), first described by Steeper and Rosai (Am J SurgPathol. 1983;7:463-475), is a rare locally infiltrative tumor that usually arises in the pelvic and perineal soft tissues of young women. Approximately 150 cases have been reported in women. Aggressive angiomyxoma has a high rate of local recurrence because of its infiltrative growth and anatomical location making complete excision with wide margins difficult. To our knowledge, 39 cases of AA occurring in men have been reported in the literature. Sites frequently involved include the scrotum, spermatic cord, inguinal region, and perineum. The gross and microscopic appearances and clinical course are similar to those described in female cases. Immunohistochemistry evaluating estrogen and progesterone receptors (ER and PR, respectively), although frequently positive in the female cases, has rarely been studied in the male cases. We report the clinicopathologic features of 4 additional cases of AA in men with particular emphasis on hormone (ER/PR) receptor status. Hormone reactivity is significant in that AA may arise from specialized hormonally responsive stromal cells of the perineum and may potentially play a therapeutic role in unresectable tumors. From our small series, hormone positivity (1 case of ER+, 3 cases of PR+) does occur in the male cases of AA, and a large number of cases should be examined to determine the frequency at which these tumors express hormone receptors.     

Pseudoangiomatous stromal hyperplasia with giant cells in the female breast. No association with neurofibromatosis?

A simultaneous finding of pseudoangiomatous stromal hyperplasia (PASH) and stromal multinucleated giant cells (MGC) in mammary tissue was previously observed in patients with type-1 neurofibromatosis, indicating that it can represent a morphologic marker for this syndrome. Here, we present PASH with MGC occurring in the left breast of a 39-years-old woman who does not have neurofibromatosis. This case, along with two additional ones reported previously, indicates that PASH with MGC in the female breast may not be associated with neurofibromatosis.     

Aspiration biopsy of nodular pseudoangiomatous stromal hyperplasia of the breast: clinicopathologic correlates in 10 cases

Nodular pseudoangiomatous stromal hyperplasia (PASH) of the breast is rare and often indistinguishable from fibroadenoma, clinically and on aspiration biopsy smears. We report our observations in 10 patients with PASH, evaluated by fine-needle aspiration (FNA) biopsy and core biopsy. We retrospectively reviewed the clinical, radiographic, cytologic, and histologic findings in 10 cases of pure nodular PASH. Ten patients with a presumed clinical and radiologic diagnosis of fibroadenoma underwent aspiration biopsy. The aspiration smears were diagnosed as fibroadenoma (4 cases), cellular fibroadenoma (1 case), schwannoma versus neurofibroma (1 case), fibrocystic change (3 cases; 2 with atypia), and "not specific for a lesion" (1 case). A diagnosis of PASH was not suspected in any case. A discrepant or imprecise cytologic diagnosis and/or the presence of dissociated spindle or epithelial cells, or cellular stromal fragments prompted a surgical excision in 7 of 10 patients (70%). The remaining 3 patients exhibited cytologic features of fibroadenoma and were diagnosed as such; however, surgical excision was recommended. Three patients underwent a subsequent core biopsy, with a diagnosis of PASH being made in 1 patient. FNA biopsy could not discriminate PASH from fibroadenoma in 4 of 10 patients (40%) or suggest a diagnosis of PASH in any case. On retrospective review, the finding of plump, spindle-shaped mesenchymal cells may be a cytologic clue to suggest a diagnosis of PASH.     

Inhibin expression in ovarian-type stroma in mucinous cystic neoplasms of the pancreas.

Mucinous cystic neoplasms (MCNs) of the pancreas are typically found in middle-aged to elderly women and contain ovarian-type stroma in the cyst wall. Whether the resemblance of this stroma to ovarian stroma is only morphologic or has more functional similarity is still unclear. Estrogen receptors (ER) and progesterone receptors (PR) have been shown to be expressed in a wide variety of tissues and tumors, including the ovarian-type stroma of MCN. Inhibin, on the other hand, has been shown to have a more restricted expression, limited to ovarian sex cord-stromal components and placental cells, and has recently been shown to be expressed in pancreatic MCNs. However, it is still unclear whether this expression is limited to MCNs of the pancreas and whether it has any diagnostic role. Seven cases of MCN (4 mucinous cystadenoma, 2 borderline MCN, and 1 mucinous cystadenocarcinoma with microinvasion), 6 cases of intraductal papillary mucinous tumor, 1 of mucinous cystic tumor of uncertain classification, 2 of mucinous noncystic adenocarcinoma, 4 of serous cystadenoma, and 4 solid pseudopapillary neoplasms were selected for this study. Five cases with normal pancreatic tissue were included as controls. Immunohistochemical stains for alpha-inhibin, ER, and PR were performed on a representative section from each case on formalin-fixed, paraffin-embedded tissue sections using a standard indirect immunoperoxidase method. All cases of MCN were in female patients with an average age of 55.3 years, showing ovarian-type stroma and clusters of alpha-inhibin-positive luteinized theca-like cells. In all these cases, moderate to strong PR positivity was also noted in the ovarian-type stroma, including many of the alpha-inhibin-positive luteinized theca-like cells. ER was expressed in 2 cases. The epithelial cells of MCNs were all negative for ER, PR, and alpha-inhibin staining. Of the other tumors, 4 solid pseudopapillary neoplasms showed positivity for only PR in the tumor cells. The remaining tumors were negative for all markers. In conclusion, the finding of alpha-inhibin positivity in MCN with ovarian-type stroma further supports its similarity to true ovarian stromal tissue and may suggest a role of complex hormonal interaction in the pathogenesis. In addition, its limited expression in MCNs of the pancreas may be diagnostically useful in difficult cases.     

Expression of progesterone receptors in solid-cystic tumour of the pancreas

A role for sex hormones in the pathogenesis of solid-cystic tumour (SCT) of the pancreas is suggested by its predilection for young fertile women. Controversial data have been provided for the presence of progesterone receptors (PR) and/or oestrogen receptors (ER) in SCT. We report the immunohistochemical detection of PR in ten cases of SCT. Eight were from young women. The remaining two were from a post-menopausal woman and a young boy. All cases showed PR immunoreactivity in the large majority of neoplastic cells, whereas none exhibited ER positivity. In one tumour two types of cell populations were noted, the more anaplastic invasivetype being PR negative, whereas the more typical was PR positive. PR immunoreactivity in the absence of ER may simply reflect a lower sensitivity of ER antibody failing to reveal the biochemically detectable ER, or that the PR in cells of SCT are constitutively synthesized in an oestrogen-independent way, as in T47D breast carcinoma cell line, meningioma cells and some gastric cancer cells. Our findings support the hypothesis of a possible pathogenetic role of progesterone in SCT, independent of the patient's sex and age.     

Aggressive angiomyxoma of pelvic parts exhibits oestrogen and progesterone receptor positivity

AIMS: Aggressive angiomyxoma of pelvic parts is a distinctive soft tissue tumour that chiefly involves the vulvar and perineal region of female patients. Several previous reports have demonstrated oestrogen receptor (ER) and/or progesterone receptor (PR) positivity in this neoplasm. The aim of this study was to confirm whether ER and/or PR positivity is present in aggressive angiomyxoma. We also wished to ascertain whether positivity may be found in the stromal cells of normal vulval skin and in other lesions at this site that can cause diagnostic confusion with aggressive angiomyxoma. METHODS: Five aggressive angiomyxomas in female patients and one involving male pelvic soft parts were stained immunohistochemically with antibodies against ER and PR. Other samples studied were normal vulval skin (n = 7), fibroepithelial polyps of vulva (n = 7), vulval smooth muscle neoplasms (n = 5), vulval nerve sheath tumours (n = 2), vaginal angiomyofibroblastoma (n = 1), and pelvic myxoma (n = 1). Nuclear staining was classified as negative, weak, moderate, or strong and the proportion of positively staining cells was categorised as 0, < 10%, 10-50%, or > 50%. RESULTS: All five cases of aggressive angiomyxoma in female patients were positive for ER (two with weak intensity involving < 10% of cells and three with moderate intensity involving 10-50% of cells) and four of five cases were strongly positive for PR in > 50% of cells. The other case was negative for PR. There was no staining with antibodies to ER or PR in the single male patient with aggressive angiomyxoma. Other samples exhibiting positivity of the stromal cells for either ER or PR were normal vulval skin (five of seven, ER; two of seven, PR), fibroepithelial polyps (four of seven, ER; five of seven, PR), smooth muscle neoplasms (three of five, ER; four of five, PR), nerve sheath tumours (one of two, ER; one of two, PR), angiomyofibroblastoma (one of one, ER; one of one, PR), and pelvic myxoma (one of one, PR). CONCLUSIONS: All cases of aggressive angiomyxoma of pelvic soft parts in female patients exhibited positivity for ER and/or PR. Because of its propensity to occur in female patients during the reproductive years, it is possible that aggressive angiomyxoma is a hormonally responsive neoplasm. However, dermal fibroblasts in normal vulval skin and stromal cells in a variety of vulval lesions can also be positive. ER or PR immunoreactivity cannot be used to distinguish aggressive angiomyxoma and its histological mimics.     

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.     

Benign cystic mesothelioma of the peritoneum: a clinicopathologic study of 17 cases and immunohistochemical analysis of estrogen and progesterone receptor status

Benign cystic mesothelioma (BCM) is an uncommon lesion of the peritoneum occurring predominantly in women of reproductive age. Although most patients are managed by surgical resection, a reported high incidence of cyst recurrence has led to the use of hormonal therapy in isolated cases in an attempt to control cyst size and relieve local symptoms. To date, the estrogen receptor (ER) and progesterone receptor (PR) status of BCM has not been evaluated. Here we present our experience with 17 cases (13 women, 4 men) of BCM seen over a 19-year period, including an immunohistochemical analysis of ER and PR status in 14 cases. All lesions showed typical morphological features of BCM, and calretinin immunostaining was positive in 14 of 14 cases. Five patients experienced either 1 or 2 tumor recurrences, and no patients died of disease. One case was diffusely positive for ER only, 1 case was focally positive for PR only, and 1 case was focally positive for both ER and PR. Although immunohistochemical detection of female sex hormone receptors in BCM is uncommon, the focal presence of ER and/or PR in some lesions does provide weak biologic support for the use of hormonal manipulation as a therapeutic option. Hum Pathol 34:369-374.     

Estrogen and progesterone receptor expression in uterine and extrauterine leiomyosarcomas: an immunohistochemical study.

The authors have noted anecdotal cases of extrauterine leiomyosarcomas (LMS) with estrogen receptor (ER) and progester-one receptor (PR) immunoreactivity. However, there are few studies that have compared ER and PR immunoexpression in LMS of uterine and extrauterine origin. The authors obtained a representative formalin-fixed, paraffin-embedded tissue block from cases of uterine LMS (n = 15) and extrauterine LMS (n = 16) from the archives of the Cleveland Clinic Foundation and performed immunohistochemical staining for ER and PR. Staining was evaluated by 2 observers in a semiquantitative manner using the following scale: 0, no nuclear staining; 1+, 1 to 25% of nuclei stained; 2+, 26 to 50% of nuclei stained; 3+, 51 to 75% of nuclei stained; 4+, 76 to 100% of nuclei stained. The majority of uterine LMS stained for ER (13 of 15, 87%), PR (12 of 15, 80%), or both ER and PR (12 of 15, 80%), with most cases showing 3+ or 4+ positive staining. For the extrauterine LMS cases, staining for ER was seen in 4 of 16 cases (25%), staining for PR was observed in 2 of 16 cases (13%), and staining for both ER and PR was seen in 2 of 16 cases (13%). One extrauterine LMS showed 4+ coexpression of ER and PR, but the remaining extrauterine cases showed only 1+ ER and/or PR immunoreactivity. These data suggest that most uterine LMS coexpress ER and PR, and most extrauterine LMS do not stain for these antigens. However, a subset of extrauterine LMS are ER and/or PR immunoreactive. This raises the possibility that hormonal manipulation may be beneficial in the treatment of these therapeutically recalcitrant tumors.     

Pseudoangiomatous stromal hyperplasia of the breast-cytological features of two cases and review of literature

Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a lesion characterized on histology by the presence of anastomosing slit like spaces embedded in a hyalinized fibrous stroma. Till date, the cytological features of PASH have been described in only 12 cases, of which two cases were diagnosed on aspiration cytology as suspicious for carcinoma and in one case, for phyllodes tumor. We describe the FNAC findings of two of our cases of PASH. The first case was diagnosed as a phyllodes tumor and the other case as a benign proliferative breast disease, possibly a fibroadenoma. A review of the published literature on cytology of PASH shows the morphological variations that can exist in the cytology smears of this lesion. FNAC findings of PASH are non-specific, and the role of FNAC in PASH is to confirm the benign nature of the lesion, rather than provide a definitive pre-surgical diagnosis.     

Rapidly growing nodular pseudoangiomatous stromal hyperplasia of the breast in an 18-year-old girl

Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a rare benign proliferation of mesenchymal stromal cells with irregular slit-like formations resembling angiomatous structures. In the majority of cases this lesion is a focal microscopic finding in breast biopsies performed for benign or malignant diseases. It may present in a pure diffuse or nodular form. The exact etiology and pathogenesis of this tumor-like lesion is still unknown, but a proliferative response of myofibroblasts to hormonal stimuli has been postulated. A large 12 x 9 x 3.5 cm rapidly growing nodular form of PASH of the breast in an 18-year-old woman is here described with clinical and histological findings. A possible hormonal etiology was indicated by elevated progesterone (three-fold) and decreased estrogen serum levels. Different diagnostic lesions, such as giant fibroadenoma and low-grade angiosarcoma, are discussed. To the authors' knowledge this is only the fourth case of nodular PASH of the breast reported in the English literature.     

Fine-needle aspiration cytology of pseudoangiomatous stromal hyperplasia of the breast

Pseudoangiomatous stromal hyperplasia (PASH) is an uncommon lesion usually found in premenopausal women. Histologically, it is characterized by complex, anatomosing, empty slit-like spaces in a dense collagenous stroma. These pseudoangiomatous spaces are lined by monomorphic spindle cells of myofibroblastic differentiation. Cytological features of PASH are rarely discussed and reported, and may pose diagnostic challenge to surgical pathologists. Two cases of PASH are reported with emphasis on the FNAC features and cytologic differentiation from other benign fibroepithelial lesions.     

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.     

Gynecomastia in type-1 neurofibromatosis with features of pseudoangiomatous stromal hyperplasia with giant cells. Report of two cases

We describe the histological finding in two cases of gynecomastia in patients with von Recklinghausen's disease. The histological and immunohistochemical features of the two cases were reviewed and compared with those of five cases of gynecomastia in men without clinical evidence of neurofibromatosis. In both patients bearing von Recklinghausen's disease, the breast stroma showed features consistent with pseudoangiomatous stromal hyperplasia (PASH). It was characterised by anastomosing empty spaces lined by spindle and multinucleated giant cells which were positive with CD34 and anti-vimentin antisera and negative with anti-FVIII and CD31 antisera. In two of five of the control cases without neurofibromatosis, the mammary stroma showed focal areas with features of PASH, but no multinucleated giant cells were present in any case. PASH with giant cells should be recognised as a feature of gynecomastia in von Recklinghausen's disease. The presence of multinucleated giant cells is very unusual and, although more cases have to be studied, these cells seem to be a feature of PASH occurring in patients with von Recklinghausen's disease.     

子宫浆液性癌及内膜上皮内癌临床病理分析

目的探讨子宫浆液性癌(USC)及内膜上皮内癌(EIC)的组织病理学特点及鉴别诊断。方法回顾性分析13例USC和1例EIC的临床和病理学特点,并进行免疫组化染色观察p53、ER和PR在肿瘤细胞中的表达。结果患者年龄60～77岁(平均68岁),临床多表现为绝经后不规则阴道流血。随访10例,6例死亡,生存5～28个月(平均14个月);4例仍存活(11～36个月)。9例为单纯USC,4例混合有其他类型内膜腺癌成分。形态上,9例USC以有纤维血管轴心的宽乳头为主,被覆异型性明显的多角形或鞋钉样细胞,2例肿瘤大部分为纤细的乳头结构,1例以腺管状结构为主。2例表现为息肉表面的EIC,无间质浸润和腺体融合。3例USC的浸润成分以腺管结构为主。7例USC伴有EIC,其中2例宫颈内口、1例输卵管黏膜也可见上皮内癌改变。免疫表型:12例USC和所有EIC病变的非典型细胞对p53呈弥漫性强阳性反应,各有1例USC有ER、PR阳性表达。结论USC结构有一定的多样性,可以表现为分化好的腺管状结构。内膜活检标本中发现EIC改变时,提示可能有USC存在。应仔细检查绝经后妇女的内膜息肉以排除EIC改变。p53、ER、PR免疫组化染色有助于鉴别诊断。     

Quantitative enzyme immunoassay and semiquantitative immunohistochemistry of oestrogen and progesterone receptors in endometriotic tissue and endometrium.

BACKGROUND: The capacity of different tissues to respond to steroids has been evaluated mainly according to the concentrations of oestrogen (ER) and progesterone (PR) receptors, which may be assayed either in tissue homogenates or histochemically. These two principles have been used in different studies of endometriotic tissue, giving somewhat different results, probably because the tissue is heterogeneously mixed with fibrotic tissue and blood cells to various degrees. AIMS: To compare a quantitative and a qualitative, semiquantitative immunocytochemical assay for ER and PR in a heterogenous tissue (endometriotic) and a similar but more homogenous tissue (endometrium). METHODS: ER and PR concentrations were measured using enzyme immunoassay (EIA) and immunocytochemistry (ICA) in the same tissue samples (endometriotic tissue from 31 women and endometrium from 19 of the same women). RESULTS: There was a significant correlation between PR concentration (using EIA) and semiquantitation of PR using PRICA in endometrial epithelium (p = 0.028). The correlation between the two techniques for ER concentration was not significant. In endometriotic tissue no correlation was found between the two techniques for ER or PR. CONCLUSIONS: These data show that in heterogeneous tissues like endometriotic tissue different techniques for measuring steroid receptors may produce substantially different results. The two techniques (EIA and ICA) are complementary and a combination of the two techniques might aid in determining optimal treatment.     

Steroid hormone receptor expression in nasopharyngeal angiofibromas. Consistent expression of estrogen receptor beta

Nasopharyngeal angiofibroma is an uncommon tumor arising in adolescent males, suggesting that the tumor may be hormonally responsive. Previous studies have found androgen receptor (AR) expression but variable expression of estrogen receptor (ER). The recently described ss receptor for estrogen has not been analyzed in angiofibroma. We analyzed 13 cases of nasal angiofibroma by immunohistochemical analysis for the presence of ARs, progesterone receptors (PR), and ER-a and ER-ss. All 13 cases were positive for ER-ss, in stromal pericytic and endothelial cells, and 12 of 13 stained strongly. Five cases were positive for AR in stromal cells, most staining weakly, and with no staining in endothelial or pericytic cells. None of the cases displayed staining for ER-a or PR. The findings confirm that nasopharyngeal angiofibromas express ER and suggest that new modulators of ER-ss activity may provide an alternative therapy for these lesions.     

Estrogen and progesterone receptor detection in archival formalin-fixed, paraffin-embedded tissue from breast carcinoma: a comparison of immunohistochemistry with the dextran-coated charcoal assay.

The steroid receptor (estrogen (ER) and progesterone receptor (PR] status was studied in 94 cases of invasive breast carcinoma from three separate institutions. All cases had fresh tissue examined for ER and PR by the dextran-coated charcoal cytosolic assay (DCC), and each case was examined immunohistochemically for ER and PR from archival formalin-fixed, paraffin-embedded tissue. Immunohistochemical assays (IH) were reviewed blinded to the DCC results and scored in a semiquantitative fashion prior to comparison to the DCC results. Overall, there was agreement between DCC and IH in 89% of ER and in 87% of PR assays. Some 50% of the ER discorrelations were of the IH-positive DCC-negative type, while 27% of the PR discorrelations were of this type. In four cases, both ER and PR did not correlate between IH and DCC determinations, with two being IH (ER and PR) positive and DCC negative, and two of the opposite type. The results of the study show that steroid receptor assays performed on routinely processed formalin-fixed archival material are reliable and closely recapitulate the results of traditional biochemical assays. Results suggest that, in the cases where IH is positive while DCC is negative, the IH result may actually provide a more reliable receptor status of the tumor than does the DCC result. Semiquantitation of fixed tissue IH assays shows a trend toward quantitative correlation with DCC results, but this correlation is weak, and factors concerning fixation and processing are most likely to be responsible.(ABSTRACT TRUNCATED AT 250 WORDS)