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Breast-nonmalignant

Pseudoangiomatous stromal hyperplasia (PASH) of breast

Reviewer: Hind Nassar, M.D. in January 2009 (see Authors page)

Revised: 9 October 2012, last major update April 2010

Definition

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● Benign lesion of complex, anastomosing, slit-like spaces, that are either acellular or composed of spindled cells

● First described in 1986 (Hum Path 1986;17:185)

Terminology

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● Also called pseudoangiomatous hyperplasia of mammary stroma

● PASH phenomenon: cases in which PASH is an incidental microscopic finding (up to 23% of breast surgicals)

Epidemiology

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● Women 19-52 years

● Also common in men with gynecomastia (Histopathology 1995;26:463)

● Also occurs in children (Pediatr Dev Pathol 2009;12:450)

Sites

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Etiology

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● Myofibroblastic origin

Clinical features

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● Usually an incidental finding, but may produce nodular lesions or have rapid growth

Prognostic factors

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Case reports

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● 12 year old girl requiring bilateral mastectomy (Breast J 2007;13:603)

● 37 year old woman with rapidly growing tumor (Chir Ital 2009;61:369)

● Women in 40’s (Breast Cancer 2006;13:349, Archives 2002;126:223, Archives 2003;127:e41, Radiographics 1999;19:1086)

● 43 year old woman with axillary mass (Breast 2005;14:61)

● Nipple mass (Breast J 2001;7:263)

● Focal malignant features (Int J Surg Pathol 2008 Jul 8 [Epub ahead of print])

Treatment

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● Excision with 1-2 cm margins or possibly close follow-up (Mod Path 2008;21:201)

● Recurs in 10-35%

● If diffuse, may require mastectomy

● Axillary dissection not recommended since only rarely spreads to lymph nodes

● Tamoxifen may cause tumor regression (Breast J 2001;7:434) or tumor growth (Archives 2003;127:e41)

Clinical images

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Gross description (Macroscopy)

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● Usually unilateral, well circumscribed, external surface may resemble a capsule; 2-15 cm

● Cut surface is firm, gray-white, resembles fibroadenoma

● No hemorrhage or necrosis

Gross images

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Nodular lesion Multiple nodules (fig 2)

Micro description (Histopathology)

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● Proliferation of stromal elements (fibroblastic/myofibroblastic) mixed with breast ducts

● Dense keloid-like stroma has anastomosing pattern of slit-like clefts (empty spaces) lined by single layer of flat spindle cells simulating vascular spaces

● Single cells may form delicate bridges between the walls of a space

● Cellular areas or plump spindle cells may obscure pseudoangiomatous structure

● Often gynecomastia-like changes (Mod Path 2008;21:201)

● Associated with columnar cell lesion (Int J Clin Exp Pathol 2009;3:87)

● Rarely multinucleated giant cells (Breast J 2007;13:568)

● No mitotic figures, no necrosis, no atypia

Micro images

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Spindle cells at margins of slit-like spaces

Various images

Clefts and anastomosing spaces With columnar cell lesion

in dense collagenous stroma

(small blood vessel at arrow)

Clefts (but not endothelium) Spindle cells (not ductal cells) Vimentin+

are CD31 negative are cytokeratin negative spindle cells

ER-beta positive CD34+

With gynecomastia

(A: vimentin, B: CD34)

Virtual Slides

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Virtual slide

Videos

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Cytology description

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● Moderately cellular with cohesive clusters of bland ductal cells (occasionally with staghorn pattern), single naked nuclei, some spindle cells with moderate cytoplasm and fine chromatin

● Occasional loose hypocellular stromal tissue fragments containing spindle cells and paired elongated nuclei in fibrillary matrix (Acta Cytol 2003;47:373)

● Findings can confirm benign nature of disease, but are non-specific, resembling fibroadenoma or phyllodes tumor (Indian J Pathol Microbiol 2005;48:260)

● Finding plump spindled mesenchymal cells is suggestive (Diagn Cytopathol 2005;32:345)

Cytology images

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Positive stains

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Spindle cells:

● PR (intense, Am J Surg Pathol 1991;15:145), ER-beta, androgen receptor (Int J Clin Exp Pathol 2009;3:87), vimentin, CD34 (Am J Surg Pathol 1995;19:270)

● Variable desmin and actin

Negative stains

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Spindle cells:

● Factor VIII, Ulex, CD31, keratin

Electron microscopy descriptions

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● Spaces are not true vascular channels, but due to disruption and separation of stromal collagen fibers

Electron microscopy images

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Molecular / cytogenetics description

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Molecular / cytogenetics images

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Differential Diagnosis

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● Low grade angiosarcoma: hemorrhagic, soft, interanastomosing vascular channels containing red blood cells with invasion into breast parenchyma, papillary endothelial growth and hyperchromatic endothelial cells, CD31+, factor VIII+ (Arch Pathol Lab Med 2009;133:1335)

Additional references

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● Stanford University

End of Breast-nonmalignant > Benign tumors / changes > Pseudoangiomatous stromal hyperplasia

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