Concurrent giant tumoral pseudoangiomatous stromal hyperplasia necessitating bilateral mastectomy.

Pseudoangiomatous stromal hyperplasia (PASH) is an uncommon benign mesenchymal tumor of the breast. Majority occur as diffuse lesions, and diagnosis is often incidental or in a background of other breast pathologies. Bilaterality with multiple tumoral masses in giant breasts is a rarity. We report a 34-year-old nonlactating female with 2-year history of rapid progressive painless bilateral enlargement of the breasts following surgical excision of ill-defined breast lumps which were not subjected to histopathological evaluation a year earlier. Examination revealed bilateral nontender giant breasts extending to the umbilical area with masses which were not attached to overlying skin, Grade 2 pressure ulcers on the lateral posterior breast aspects bilaterally and peau d'orange. There were no other palpable masses or lymph nodes. A clinical assessment of bilateral gigantomastia was made. Bilateral mastectomy revealed giant PASH which was confirmed with positive immunohistochemical reactivity for CD34 and vimentin. No other breast pathologies were seen with extensive sectioning. Diffuse multiple breast lesions with incomplete excision are associated with rapid growth in PASH as seen in this case. The presence of concurrent bilateral giant tumoral masses without any underlying breast pathology is a novelty. The mainstay of treatment in this case is mastectomy despite its benign nature.

INTRODUCTION

Pseudoangiomatous stromal hyperplasia (PASH) was first described by Vuitch et al. in 1986.[1] It is an uncommon benign mesenchymal tumor of the breast in predominantly premenopausal females though it can be seen in any reproductive-aged female.[23] It is rarer still in postmenopausal females.[2] PASH cases have also been documented in males with gynecomastia.[45] The majority of PASH occur as ill-defined diffuse lesions of sizes ranging from 3 to 7 cm averagely. Quite often, the diagnosis is incidental or made in a background of other mainly benign proliferative breast pathologies such as fibroadenoma, stromal fibrosis, phyllodes, and atypical ductal or lobular hyperplasia. Although PASH coexisting with ductal cell carcinoma in situ and invasive carcinoma has been reported.[26] PASH is also a great mimic of vasoformative proliferative lesions. However, the occurrence of PASH as multiple tumoral masses concurrently in both breasts is a rarity.

CASE REPORT

A 34-year-old single female presented to the surgical outpatient department of our hospital with a 2-year history of progressive painless bilateral enlargement of the breasts, back pain, and dragging sensation. She also noticed large swellings in the breast with no associated nipple discharge or history of lactation. A year before presentation, she had excisional biopsies of masses from both breasts at a general hospital for suspected fibroadenoma; however, no histopathological diagnosis was made. She noticed accelerated enlargement a few weeks postsurgery with the subsequent development of pressure ulcers on both posterior lateral breasts surfaces and bilateral peau d’orange. She had no constitutional symptoms of fever, headache, respiratory difficulty, or swellings anywhere else. However, there was associated feeling of social embarrassment in public because of her massive breasts. There was no family history of breast disease or similar enlargement or contraceptive use. She had also termination of a 2-month gestation 10 years ago.

Clinical examination was of a young middle-aged female with temperature of 36.5°C. Significant findings were bilateral huge nontender breasts with huge masses extending to the umbilical area. The nipples were inverted. The masses were not attached to the overlying skin. There were distended veins, peau d’orange, and Grade 2 pressure ulcers on the lateral aspect of posterior side of both breasts. Previous surgical scars were also seen on the lateral aspect of both breasts. There were no other palpable masses or lymph nodes in the axilla or cervical regions. A clinical assessment of bilateral gigantomastia secondary to fibroadenoma or phyllodes tumor was made. She had ultrasound scanning of both breasts which revealed parenchymal and ductal hypertrophy of both breasts with multiple cysts and masses and fine-needle aspiration cytology (FNAC) of both breasts. The two procedures gave a diagnosis of a benign breast disease. She was counseled on breast reduction surgery, but she opted for bilateral mastectomy because she was apprehensive of another recurrence and further increment in the breast sizes as seen with the first surgery at the general hospital. She opined that the initial surgery precipitated the current massive sizes of the breasts. The mastectomy specimens were received in the pathology laboratory, and grossly, the right and left breasts weighed 10 and 9 kg, respectively, with deep surface ulcerations on the posterior aspect [Figure 1]. The right breast measured 38 cm × 35 cm × 12 cm while the left measured 37 cm × 34 cm × 11 cm. Serial sectioning revealed numerous discreet gray-white nodules and gelatinous areas on the cut surfaces [Figure 2]. Hematoxylin- and eosin-stained tissue microscopy revealed numerous anastomosing slit-like pseudoglandular spaces lined by spindle cells and separated by thick hyalinized collagen bundles [Figure 3]. The spindle cells showed positive immunohistochemical reactivity for CD34 [Figure 4] and vimentin [Figure 5] and were nonreactive for Ki67 and S100. The residual breast tissues were unremarkable. No other breast pathologies were seen. She is well after 6-month follow-up.

Figure 1

Right and left mastectomy specimens weighing 10 and 9 kg, respectively

Figure 2

Cut surfaces showed numerous discrete gray-white nodules and gelatinous surfaces

Figure 3

Right breast: numerous anastomosing slit pseudoangiomatous spaces lined by spindle cells and separated by thick hyalinized collagen bundles. H and E, ×100

Figure 4

The spindle cells showed positive immunohistochemical reactivity for CD34, ×100

Figure 5

The spindle cells showed positive immunohistochemical reactivity for vimentin, ×100

DISCUSSION

PASH is a myofibrous tumor with varying proportions of myoid and fibroblast differentiation. It is a histologic mimic of vasoproliferative lesions due to the formation of slit-like spaces simulating vascular channels, hence its name.[3] PASH has been etiologically linked to hormonal influence due to its responsiveness to hormonal receptors and its occurrence in gynecomastia.[2478] It is commonly seen in reproductive-aged females and predominant in premenopausal state though rare cases have been documented in males.[4] Despite its wide age of presentation which ranges from 3 to 86 years with an average of 37–51 years[3] in one review and the 12–65 years age range in the report of Gresik et al., it is uncommon in postmenopausal females, and when it occurs, there is usually a history of hormone replacement therapy.[67] It is rarer still in children and the youngest documented case was in a 3-year-old child.[9]

Presentation is usually of a nodular unilateral painless breast mass averaging 5–7 cm, frequently located in the upper outer quadrant of the breast, though any part of the breast may be involved. Our patient presented with concurrent bilateral diffuse giant tumoral masses averaging 37.5 cm. Concurrent PASH has been reported in literature. However, they were not diffuse, giant, or tumoral as seen in this case. Our patient also presented with skin ulcers and peau d’orange due to pressure effect on the lymphatic drainage of the breast from the huge masses, thus simulating a malignant process. Similar peau d’orange has been reported in pregnant females with PASH-associated huge breasts.[10]

The diagnosis of PASH is often an incidental microscopic finding alongside other proliferative breast diseases. Majority of affected patients present for other breast diseases such as fibroadenoma, phyllodes, fibrocystic change, atypical ductal hyperplasia, and atypical lobular hyperplasia where PASH may coexist as a part of the proliferating changes rather than a separate disease.[3] The mainstay of diagnosis is tissue biopsy where characteristic complex anastomosing empty spaces lined by myofibroblasts are seen in an abundant collagenous stroma admixed with a few epithelial components with varying proliferative breast changes. It is important to differentiate histological mimics of PASH, in particular angiosarcoma of the breast which is a malignant tumor.[8] The pseudovascular spaces may be mistaken for vascular spaces but are completely lacking in endothelial lining. Definitive diagnosis is usually achieved using immunohistochemical antibody makers such as CD34, vimentin, factor VIII, D2-40, and Ki67 for confirmation.[28] This case was positive for CD34 and vimentin only by staining the spindle cells component. Whereas it is the endothelial lining cells that stain positively in vascular lesions with CD34, factor VIII, D2-40, and CD31. The Ki67 is, particularly, useful in determining the proliferative capacity of any tumor and was negative in this case, further confirming its benign nature. Other immunohistochemical antibody markers of variable utility include estrogen receptor, smooth muscle actin, and cytokeratin.[23]

S100 was done in this case to differentiate the lesion from other fibrohistiocytic lesions and desmoplastic melanoma which is another histological mimic of all tumors.

Other useful diagnostic methods include mammography, ultrasonography, and magnetic resonance imaging.[11] A few authors have also made diagnosis based on FNAC though this might be fraught with errors.[12] She had FNAC which was not diagnostic but confirmed the benign nature of her breast disease.

The treatment of PASH is surgical excision though recurrences have been recorded. Recurrent lesions are often managed with wide excision and rarely require mastectomy. Our patient had bilateral mastectomy despite the benign nature of PASH due to the giant tumoral and diffuse nature of her lesions, rapid progressive growth as well as a history of recurrence. Diffuse multiple lesions with incomplete excision are often associated with rapid growth. In conclusion, giant PASH as seen in this case may require mastectomy despite its benign nature and absence of other breast pathologies.

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