Pseudoangiomatous Stromal Hyperplasia (PASH)

Stromal Fibrosis

Age

Any age, usually premenopausal women, association with contraceptive use; postmenopausal women on hormone therapy; men with gynecomastia

Adolescents and premenopausal women

Location

Anywhere in the breast

Anywhere in the breast

Presentation

Clinical mass or incidental finding

Clinical mass or incidental finding

Imaging findings

Mammographic mass without calcification; on ultrasound, a well-defined hypoechoic mass; MRI may show non-mass-like enhancement

None or parenchymal distortion

Etiology

Hormone imbalance, aberrant response to hormones

Unknown

Histology

1. 
   

   Myofibroblastic proliferation usually well demarcated (Fig. 8.1.1)

   
   
2. 
   

   Myofibroblasts form slit-shaped, pseudovascular spaces devoid of red blood cells within a dense, keloid-like stroma (Figs. 8.1.2 and 8.1.3)

1. 
   

   Periductal and perilobular fibrosis, may form a discrete mass (Fig. 8.1.4)

   
   
2. 
   

   Fibrosis consists of dense collagen of low cellularity (Fig. 8.1.5)

   
   
3. 
   

   Associated epithelial elements often atrophic (Fig. 8.1.4)

   
   
4. 
   

   Occasional true vascular spaces (capillaries and lymphatic spaces) are present (Fig. 8.1.6)

Special studies

None routinely needed. The cells lining the pseudovascular spaces express vimentin and CD34, and are negative for Factor VIII and CD31.

None

Genetic abnormalities

None

None

Treatment

PASH is a benign process which requires excision only for cosmesis and to eliminate discomfort

None

Clinical implication

None

None

Nodular Fasciitis

Fibromatosis

Age

Adult women, occasionally occurs in men, wide age range

Wide age range, more common in women but may occur in men

Location

Subcutis of the breast or less commonly within the mammary parenchyma

Most frequently arises from the pectoral fascia and extends into the breast but may occasionally originate within the breast parenchyma

Presentation

Mass; history of rapid growth and tenderness

Single nontender palpable mass; may be accompanied by skin retraction or dimpling; rarely bilateral

Imaging findings

Mass, frequently with infiltrative margins mammographically. On ultrasound, homogeneous, hypoechoic, solid mass with a border often obscured by normal tissues.

Spiculated mass

Etiology

Usually history of trauma, although eliciting that history may be difficult

Unknown; may be associated with previous trauma, surgery, and breast implants

Histology

1. 
   

   Dense, nodular, well-circumscribed proliferation of myofibroblasts lacking a capsule (Fig. 8.2.1)

   
   
2. 
   

   Plump fibroblastic and myofibroblastic cells arranged in short fascicles in edematous stroma (Fig. 8.2.2)

   
   
3. 
   

   Hemorrhage common (Fig. 8.2.3)

   
   
4. 
   

   Edematous, occasionally myxoid stroma, containing lymphocytes, erythrocytes, and thin-walled vessels; stromal changes often described as “tissue culture” fibroblastic proliferation (Figs. 8.2.3 and 8.2.4)

   
   
5. 
   

   Mitoses and osteoclast-like giant cells may be present

1. 
   

   Poorly circumscribed mass (Fig. 8.2.5)

   
   
2. 
   

   Locally infiltrative stromal neoplasm composed of long sweeping, intersecting fascicles of bland fibroblasts and myofibroblasts (Figs. 8.2.6 and 8.2.7)

   
   
3. 
   

   Variable cellularity, with the more cellular regions usually present at the periphery (Fig. 8.2.5)

   
   
4. 
   

   Perivascular hemorrhage; no (or rare) mitotic figures

   
   
5. 
   

   Dense collagen resembles a keloid (Fig. 8.2.7)

   
   
6. 
   

   Irregular “tongues” of cellular stroma extend into fat (Figs. 8.2.5, 8.2.6, and 8.2.8)

Special studies

Expresses the muscle marker actin; desmin positivity rare. Keratin, S100, and CD34 usually negative.

Cytoplasmic expression of actin and nuclear expression of β-catenin in 80% of cases. Desmin and S-100 expression may be detected in a minority of cells. Fibromatosis is negative for expression of cytokeratins, BCL-2, CD34, estrogen (ER), progesterone (PR), and androgen receptors (AR).

Genetic abnormalities

Recurrent MYH9-USP6 gene fusions

May arise in patients with familial adenomatous polyposis coli (FAP), but most are sporadic. Activating mutations in β-catenin gene reported in 45% of cases, mutations in FAP or 5q loss reported in 33% of cases.

Treatment

None. When characteristic histologic features are present in the appropriate clinical setting, observation is sufficient, with the expectation that the mass will eventually resolve.

If anatomically feasible, wide local excision to obtain negative margins should be undertaken to minimize the risk of local recurrence. Radiation and chemotherapy ineffective and not indicated.

Clinical implication

None. Local recurrence infrequent.

Local recurrence in 20%-30% of cases, usually within 3 y of original diagnosis; lacks metastatic potential

Fibromatosis

Scar

Age

Wide age range, more common in females

Middle age to older women

Location

Most frequently arises from the pectoral fascia and extends into the breast but may occasionally originate within the breast parenchyma

Prior surgical or trauma site, near implants

Presentation

Single, nontender, palpable mass; may be accompanied by skin retraction or dimpling; rarely bilateral

History of prior breast biopsy/surgery, including implants

Imaging findings

Spiculated mass

Architectural distortion, dystrophic calcifications, and asymmetry

Etiology

Unknown; may be associated with previous trauma, surgery, and breast implants

Prior breast biopsy/surgery, including implants, ruptured cyst, resolving fat necrosis

Histology

1. 
   

   Poorly circumscribed mass (Fig. 8.3.1)

   
   
2. 
   

   Locally infiltrative stromal neoplasm, composed of long sweeping, intersecting fascicles of bland fibroblasts and myofibroblasts (Figs. 8.3.2 and 8.3.3)

   
   
3. 
   

   Variable cellularity, with the more cellular regions usually present at the periphery

   
   
4. 
   

   Pericapillary hemorrhage; no (or rare) mitotic figures

   
   
5. 
   

   May invade into normal structures

1. 
   

   Composed of dense collagen containing sparse fibroblasts (Fig. 8.3.4)

   
   
2. 
   

   Interspersed foamy macrophages, foreign body giant cells, foci of fat necrosis, hemosiderin-laden macrophages, and neovascularization (Figs. 8.3.5 and 8.3.6)

Special studies

Cytoplasmic expression of actin and nuclear expression of β-catenin in 80% of cases. Desmin and S-100 expression may be detected in a minority of cells. Fibromatosis is negative for expression of cytokeratins, BCL-2, CD34, ER, PR, and AR.

Lacks nuclear β-catenin expression

Genetic abnormalities

May arise in patients with FAP, but most are sporadic. Activating mutations in β-catenin gene reported in 45% of cases; mutations in FAP or 5q loss reported in 33% of cases.

None

Treatment

If anatomically feasible, wide local excision to obtain negative margins should be undertaken to minimize the risk of local recurrence. Radiation and chemotherapy ineffective and thus not indicated.

None, excision for cosmesis only

Clinical implication

Local recurrence in 20%-30% of cases, usually within 3 y of original diagnosis; lacks metastatic potential

None

Fibromatosis

Fibromatosis-like Metaplastic Carcinoma

Age

Wide age range, more common in females than males

Middle age women 50-70 y, similar to age range of invasive carcinomas of no special type

Location

Most frequently arises from the pectoral fascia and extends into the breast, but may occasionally originate within the breast parenchyma

Anywhere in the breast

Presentation

Single, nontender, palpable mass; may be accompanied by skin retraction or dimpling; rarely bilateral

Mammographic or palpable mass

Imaging findings

Spiculated mass

Spiculated mass or architectural distortion

Etiology

Unknown; may be associated with previous trauma, surgery, and breast implants.

Unknown

Histology

1. 
   

   Poorly circumscribed mass (Fig. 8.4.1)

   
   
2. 
   

   Locally infiltrative stromal neoplasm composed of long sweeping, intersecting fascicles of bland fibroblasts and myofibroblasts (Fig. 8.4.2)

   
   
3. 
   

   Irregular “tongues” of lesion extend into fat (Fig. 8.4.3)

   
   
4. 
   

   Hemorrhage around capillaries; no (or rare) mitotic figures (Fig. 8.4.4)

1. 
   

   Bland spindle cells arranged in short, wavy, and storiform fascicles within collagenized and/or myxoid stroma (Fig. 8.4.5)

   
   
2. 
   

   Generally more cellular than fibromatosis, but infiltrates around normal structures and into fat, similar to fibromatosis (Fig. 8.4.6)

   
   
3. 
   

   Spindle cells have pale eosinophilic cytoplasm (Fig. 8.4.7)

   
   
4. 
   

   Nuclei range from spindled to epithelioid with minimal atypia and rare mitoses (Fig. 8.4.8)

   
   
5. 
   

   Mild mononuclear chronic inflammatory cells scattered within the stroma

Special studies

Cytoplasmic expression of actin and nuclear expression of β-catenin in 80% of cases. Desmin and S-100 expression may be detected in a minority of cells. Fibromatosis is negative for expression of cytokeratins, BCL-2, CD34, ER, PR, and AR.

Expresses nuclear p63 (Fig. 8.4.9) and p40 with variable intensity and distribution, some expression of cytokeratins, especially high molecular weight cytokeratins (Fig. 8.4.10). Several antibodies against cytokeratins (including high molecular weight cytokeratins) usually required to establish the diagnosis. ER, PR, and HER2 negative.

Genetic abnormalities

May arise in patients with familial adenomatous polyposis coli, but most are sporadic. Activating mutations in β-catenin gene reported in 45% of cases, mutations in FAP or 5q loss reported in 33% of cases.

Recurrent mutations of PIK3CA and Wnt pathway genes

Treatment

If anatomically feasible, wide local excision to obtain negative margins should be undertaken to minimize the risk of local recurrence. Radiation and chemotherapy ineffective and thus not indicated.

Excision to negative margins. Axillary lymph node sampling unnecessary unless a no special type carcinoma component is also present.

Clinical implication

Local recurrence in 20%-30% of cases, usually within 3 y of original diagnosis; lacks metastatic potential

Capable of local recurrence only