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.     

Unilateral gynecomastia and pseudoangiomatous stromal hyperplasia in neurofibromatosis: case report and review of the literature

In this article, we describe unilateral gynecomastia and pseudoangiomatous stromal hyperplasia (PASH) in a case of type-1 neurofibromatosis (NF-1). It is important to distinguish PASH from fibroadenoma clinically, and from true blood capillaries and angiosarcoma histologically. In the present case, giant multinucleated cells lined the pseudovascular spaces, which was markedly different from that of conventional breast PASH. The origin of PASH has been reported to be either the fibroblast or the myofibroblast phenotype and may be affected by endocrine signaling because many cases have been reported in premenopausal women, and cases are often estrogen (ER) and progesterone receptor (PR) positive. However, previous reports have identified PASH in NF-1 in juvenile males only, and the cases were negative for α-SMA, ER and PR. The cause and prognosis of PASH in NF-1 may be distinguished from that of conventional PASH, and mast cells, histiocytes and CD54 may play roles.     

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.     

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.     

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.     

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.     

Diagnosis of pseudoangiomatous stromal hyperplasia of the breast: ultrasonography findings and different biopsy methods

Purpose

Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a rare, benign condition that can be mistaken as a fibroadenoma on an ultrasound examination or as a low-grade angiosarcoma on a histological examination. The objective of this study was to evaluate the ultrasound features and to present biopsy methods to correctly identify PASH.

Patients and Methods

We retrospectively reviewed the data of 55 women who were diagnosed with PASH of the breast. Ultrasound features were evaluated according to the Breast Imaging Reporting and Data System (BI-RADS; American College of Radiology). The diagnostic ability of different biopsy methods such as core needle biopsy, vacuum-assisted biopsy and excisional biopsy were analyzed with the final histopathological results of surgical specimens.

Results

PASH presented as a circumscribed solid mass, with hypoechoic texture with or without heterogeneity, and a parallel orientation. The features of small, internal cysts or vascular channels and no calcifications can be used to differentiate the lesions from fibroadenomas. A core needle biopsy misdiagnosed PASH in 13 cases out of 28 cases and vacuum-assisted biopsy correctly identified PASH in all 3 cases.

Conclusion

Ultrasound features of PASH should be noted when performing a biopsy. For inconclusive cases of PASH, an excisional biopsy followed by an initial core biopsy should be performed.     

Pseudo-angiomatous hyperplasia of mammary stroma: a case with gigantomastia

Pseudo-angiomatous hyperplasia of mammary stroma (PASH) is a histopathological entity which is a microscopic fortuitous finding in mammary biopsies performed for different reasons. It may be symptomatic and appears then as a palpable lump. The term pseudo-angiomatous emphasizes the characteristic aspect of the stroma simulating a vascular tumor. We report a case of PASH in a 71 year-old woman who presented a recurring breast mass with rapid swelling of the mammary gland (70 x 60 x 20 cm) treated by mastectomy. PASH must be distinguished from a well-differentiated angiosarcoma. It is ruled out by immunohistochemistry.     

Columnar cell lesions and pseudoangiomatous hyperplasia like stroma: is there an epithelial-stromal interaction?

The significance of association between cancer and its microenvironment has been increasingly recognized. It has been shown in animal models that interaction between neoplastic epithelial cells and adjacent stroma can modulate tumor behavior. Carcinoma associated stromal cells can transform normal epithelial cells into neoplastic cells. In breast, columnar cell lesions are non-obligate precursors of low grade ductal carcinoma in situ. Columnar cell lesions can be seen intimately associated with PASH-like-stroma, a lesion we termed as CCPLS. Our aim is to investigate epithelial-stromal interactions in CCPLS and compare them to PASH without columnar cell lesions in breast core needle biopsies. Normal terminal duct lobular unit (TDLU) epithelium was seen in association with columnar cell lesions as well as PASH. Eight (8) cases of each category were examined by a panel of immunostains: CD117 (C-kit), CD34, CD105, bFGF, AR, ER-beta, MIB-1. We observed a markedly decreased expression of c-kit in columnar cell lesions compared to TDLU-epithelium. CD105 showed a quantitative increase in activated vessels in CCPLS compared to PASH. A subset of CCPLS and PASH were androgen receptor positive. A strong nuclear positivity for ER-beta is observed in the epithelium and stroma of all CCPLS cases. We conclude that (1) activated blood vessels predominate in CCPLS; (2) A molecular alteration is signified by c-kit loss in columnar cell lesions; (3) ER-beta and androgen receptor positivity indicate CCPLS are hormonally responsive lesions. Our study suggests an intimate vascular and hormone dependent epithelial-stromal interaction exists in CCPLS lesions.     

Cardiac Myxoma with Glandular Differentiation: An Immunohistochemical and Ultrastructural Study

A case of cardiac myxoma with glandular differentiation is reported. The patient did not have elements of the Carney triad or syndrome. The tumor was mainly composed of characteristic stellate cells in a focally collagenized, myxoid stroma, along with aggregates of glandular-forming epithelial cells, with mucin-containing intra- and intercellular lumina. Ultrastructurally, these gland spaces displayed short, straight microvilli and junctional complexes. The epithelial cells were positive for cytokeratin 7 and negative for cytokeratin 20. Calretinin was positive in the stellate cells and negative in the epithelial component. The potential origin from pluripotent mesenchymal cells or from seeded stem cells is hypothesized for glandular differentiation in myxomas. Further studies are required to unravel the relationship between stellate cells and the diverse heterologous components reported in these tumors.     

Mucoepidermoid carcinoma of the breast: high grade variant

The mucoepidermoid carcinoma is a very rare neoplasm of the breast which histologically resembles mucoepidermoid carcinoma in the salivary glands. It is characterized by sheets of epidermoid cells with area of definite squamous differentiation as well as glandular and cystic spaces lined by atypical mucin-secreting columnar cells. The ultrastructural findings reflect the squamous and adenomatous differentiation seen on light microscopy. The degree of histological differentiation and the infrequency of nodal metastasis suggest an indolent behaviour. This is supported by the absence of recurrence or death due to the disease in 7 of the 8 cases reported to date. Only 1 patient has had extensive axillary nodal metastasis from a mucoepidermoid carcinoma which showed large areas of poorly differentiated cells. The present case is another example of such a high grade variant in which death occurred from pulmonary and vertebral metastases within 6 mth of mastectomy. An aggressive behaviour should be predicted by the presence of a large undifferentiated component in the tumour, necrosis and prominence of mitoses.     

Intriguing Case: Myxoid Meningioma

A mucosubstance-rich myxoid meningioma that recurred twice is reported. This rare form of meningioma is a potential source of confusion with other myxoid neoplasms such as metastatic adenocarcinoma or chordoma. In addition to the usual stigmata of meningial cell differentiation, ultrastructural examination revealed spaces delineated by a network of cellular processes and enclosing loose granular and fibrillar material. This neoplasm is probably linked to the so-called microcystic meningioma but has an overt production of acid muco-substance.     

Endolymphatic Stromal Myosis with Focal Tubular-Glandular Differentiation (Biphasic Endometrial Stromal Sarcoma)

A case of low grade endometrial stromal sarcoma with tubular-glandular differentiation is reported. The tumor showed a characteristic pattern of clusters and trabeculae of spindle-shaped cells infiltrating the myometrium. Lymphatic invasion was evident. Foci of solid, alveolar pattern and cleft tubular spaces were seen. The tubular spaces were lined by a cuboidal epithelium, which at the ultrastructural level showed blunt microvilli, and between adjacent cells junctional complexes and desmosomes. Both the spindle-shaped cells and the epithelial cells were rich in cytoplasmic filaments. The latter did not react with serum containing antibody against actin using a two-layer immuno-peroxidase method. The ultrastructural resemblance between the epithelial and spindle-shaped cells favors a common cellular origin, the endometrial stromal fibroblast.     

Salivary gland monomorphic adenoma. Ultrastructural,immunoperoxidase, and histogenetic aspects.

Monomorphic adenoma of basal cell type is a salivary gland tumor believed to result from a proliferation of a single type of cell. However, ultrastructural and immunocytochemical investigations of 6 monomorphic adenomas (5 from parotid and 1 from intraoral minor salivary gland) indicate that there are two classes of these lesions, one composed of two types of tumor cells and the other wholly or predominantly made up of one type of cell (isomorphic). In the former group, the organization of the tumor cells closely mimicked that of normal and hyperplastic salivary gland intercalated ducts. Aggregates of tumor cells were arranged as an inner layer of luminal epithelial cells which were surrounded by an outer layer of cells that, in some cases, had ultrastructural and immunohistochemical features indicating myoepithelial cell differentiation. In some adenomas formed by two types of tumor cells, basal-lamina-lined extracellular spaces were identified ultrastructurally in relation to modified myoepithelial cells; such spaces had the same fine-structural features as those reported in pleomorphic adenoma and adenoid cystic carcinoma. Predominantly isomorphic adenomas were composed exclusively of luminal epithelial cells. These results indicate that despite the varied histologic patterns in the numerous subtypes of monomorphic adenoma, there is a central theme of differentiation and organization in this type of neoplasm which recapitulates the ductoacinar unit of normal salivary gland parenchyma.     

Atypical thymoma (WHO B3) with neuroendocrine differentiation: report of a case

We report a case of type-B3 thymoma manifesting neuroendocrine differentiation. The patient was a 42-year-old woman who complained of shoulder pain but had no symptoms of myasthenia gravis or anemia. The tumor was located in the anterior mediastinum and had directly invaded the pericardium and left lung. Histological examination revealed that the tumor was lobulated by bands of fibrous tissue, perivascular spaces were scattered throughout the tumor, and there were a few intraepithelial lymphocytes. The vast majority of lymphocytes in the perivascular spaces and in the lobulated tumor were immunohistochemically positive for TdT, MIC2, and CD1a. The majority of tumor cells were polygonal and medium or large in size. The tumor cells were weakly positive for synaptophysin, chromogranin A, CD56, and NSE. Small nests of small, relatively uniform polygonal cells were observed facing the fibrous bands. These cells resembled the cells of carcinoid tumors and were strongly positive for NSE, synaptophysin, chromogranin A, and CD56. Ultrastructurally, sparse dense-core granules were observed in the cytoplasm of a few tumor cells. This is a unique case of thymoma with neuroendocrine differentiation, and to the best of our knowledge this is the first such case ever reported.     

Phyllodes tumors of the breast: the role of pathologic parameters

We aimed to establish whether morphologic parameters were prognostically important in a large series of breast phyllodes tumors in Asian women. Of 335 phyllodes tumors diagnosed at the Department of Pathology, Singapore General Hospital, Singapore, between January 1992 and December 2002, 250 (74.6%) were benign, 54 (16.1%) borderline, and 31 (9.3%) malignant, based on histologic review of archival slides. Of the women, 43 (12.8%) experienced recurrences during the follow-up period. Recurrent disease was correlated with grade or classification (P = .028), stromal atypia (P = .016), stromal hypercellularity (P = .046), and permeative microscopic borders (P = .021). Multivariate analysis revealed that independent predictors of recurrence were pseudoangiomatous stromal hyperplasia (PASH) and margin status, whereby the presence of PASH and complete or negative margins reduced recurrence hazards by 51.3% and 51.7% respectively. The 7 women who died of disease during follow-up had malignant phyllodes tumor at the outset and experienced recurrences, and death was preceded by distant metastases.     

Histologic and fine-needle aspiration cytologic features of polycystic disease of the parotid glands: case report and review of the literature

Polycystic disease of the parotid glands is a rare disorder, with only eight examples to our knowledge being reported in the literature. The disease presents as a painless enlargement of one or both parotid glands and does not appear to be associated with other disease processes within the head and neck, or with polycystic disease of the kidney, pancreas, or congenital fibrosis of the liver. The histology has been well described. The overall glandular architecture is preserved but the lobules are markedly distended by cysts whose lining appears to be intercalated duct in differentiation. Characteristic eosinophilic laminated spheroliths lie in many of the cystic spaces. Aspirate smears are characterized by a relatively clean background in which are distributed histiocytes, red blood cells, and small clusters of ductal epithelial cells. Polycystic disease of the parotid glands must be differentiated cytologically from mucous retention reaction, mucoceles, benign lymphoepithelial cysts, and cystic neoplasms, including Warthin's tumor, low-grade mucoepidermoid carcinoma, cystadenoma, and papillary cystadenocarcinoma.     

MALIGNANT BRENNER TUMOR WITH PERITONEAL METASTASIS

A case of malignant Brenner tumor with peritoneal metastasis in a 67-year-old woman was reported. The multilocular cystic tumor of right ovary was 420 g in weight, and their cystic walls were covered with multilayered tumor cells showing papillary pattern very frequently. The tumor was histologically transitional cell carcinoma with occasional glandular structures but no squamous differentiation corresponding to grade 2 or 3 urinary bladder carcinoma. The pattern of benign Brenner tumor was not Identified, but there was some area of proliferating Brenner tumor. Immunohistochemically, carcinoembryonic antigen was detected in several tumor cells, especially in the intercellular spaces among them, and cytokeratin was detected only in some tumor cells. Ultrastructurallly, the malignant Brenner tumor shared many common features with the benign one and also bladder tumor. Intercellular spaces with microvilli were frequently found and thought to be important for diagnosis. The morphologic criteria of this rare tumor are discussed.