Introduction
Breast carcinoma, the most common malignancy in women, is rarely diagnosed in men.
Approximately 1,910 new cases of breast carcinoma in men are reported annually
1
compared with more than 230,000 new cases in women.
2
Most male cases (90%) are of the invasive ductal subtype.
3
The lifetime risk of breast cancer for men in the general population is 0.1%.
1
Genetic predisposition significantly heightens this risk, with mutations in BRCA2
increasing the lifetime risk to an estimated 5% to 10%.
1
Inactivation of other tumor suppressors, including BRCA1, PTEN, p53, and CHEK2, is
also found to confer an increased risk in men.1, 3 Congenital disorders such as Klinefelter's
syndrome contribute to at least 3% of the incidence of all male breast cancer.
1
We report a 77-year-old man presenting with a painful right axillary mass diagnosed
as metastatic carcinoma of unknown primary. Despite multiple treatment modalities,
his disease progressed to the brain, lungs, and skin as carcinoma en cuirasse. Histopathologic
diagnosis at autopsy was pleomorphic lobular carcinoma (PLC), an uncommon subtype
of breast cancer that is reported rarely in men.
Case report
A 77-year-old man with a 50-pack-year smoking history presented to our institution
with an enlarging, painful, right axillary mass. Fine-needle aspiration and excisional
biopsy were consistent with metastatic carcinoma of unknown primary. Histology testing
found infiltrates of tumor nodules with large, pleomorphic, poorly differentiated
epithelial cells extending into the surrounding fibrofatty tissue and lymphatics.
Immunohistochemical stains were positive for cytokeratin 7 and epithelial-membrane
antigen but negative for lymphocytic markers (CD3, CD20, CD45), caudal type homeobox
gene 2 (CTH2), prostate-specific antigen (PSA), progesterone receptor (PR), estrogen
receptor (ER), and thyroid transcription factor 1 (TTF1). Computed tomography (CT)
scan of the chest found right axillary and subpectoral adenopathy (Fig 1). Positron
emission tomography/CT scan found fluorodeoxyglucose uptake in the right neck and
chest consistent with a neoplastic process.
The patient received multiple treatment modalities, complicated by intermittent periods
of poor follow-up. Therapy included 5 cycles of carboplatin and paclitaxel, 1 cycle
of docetaxel, and palliative radiotherapy. Fourteen months after initiating treatment,
a workup for dyspnea found malignant effusion and brain metastases.
The patient was referred to hospice care; however, 3 months later, he presented with
worsening dyspnea. At this time, the right anterior chest wall and neck were encased
in an erythematous, sclerotic plaque, composed of approximately 0.5- to 1.0-cm firm
papules, sparing the nipples (Fig 2, A). The affected skin showed a peau d'orange
appearance with peripheral papulonodules and pseudovesicular papules (Fig 2, B). The
ipsilateral arm was exquisitely tender with 4 + pitting edema. CT scan found complete
collapse of the right lung with massive pleural effusion; irregular, nodular, soft-tissue
densities were seen on the right anterior chest wall, suspected to be the primary
source. On brain magnetic resonance imaging, metastases had enlarged and several new
enhancing lesions were noted. Skin biopsy found epidermal spongiosis with interstitial
fibrosis and thickened collagen bundles in the dermis. Atypical cells infiltrating
in a single file pattern and abundant mucin deposition were found (Fig 3). Immunohistochemistry
was positive for cytokeratin 7, and negative for cytokeratin 20, TTF1, PSA, and CTH2,
consistent with carcinoma. Shortly thereafter, he died of a septic episode.
At autopsy, the pericardial sac and pleura were studded with white, firm nodules,
and the skin showed metastatic carcinoma. Immunohistochemistry was positive for pan
cytokeratin, gross cystic disease fluid protein 15, and mammaglobin and negative for
E-cadherin, ER, PR, and HER2/neu. The final pathologic diagnosis was pleomorphic lobular
carcinoma of the breast, apocrine subtype, with metastases to skin, brain, lungs,
pleura, pericardium, diaphragm, chest wall muscle, and lymph nodes.
Discussion
Invasive lobular carcinoma of the male breast is rare, owing to the absence of lobules
and acini in male breast tissue, representing only 1% of male breast cancer.
3
PLC is an uncommon highly aggressive subtype, with few reported cases in men.
4
PLC often presents at an advanced stage, is likely to be larger with more positive
lymph nodes at time of diagnosis, and carries an increased risk of lymphovascular
invasion and distant metastases.
5
Cytologically, it is characterized by enlarged nuclei, prominent nucleoli, increased
hyperchromasia, frequent mitotic figures, and eosinophilic cytoplasm.5, 6 Histologically,
PLC shows loss of E-cadherin expression and no expression of ER and PR and has a high
rate of HER2/neu gene amplification.
6
However, HER2 gene amplification appears to be variable in male PLC cases.
4
In this patient, the apocrine subtype was suspected, associated with significantly
more genomic alterations than the nonapocrine type.
6
Breast cancer is a common malignancy to metastasize to the skin. Carcinoma en cuirasse,
a distinct clinicopathologic type of cutaneous metastasis, was coined by Velpeau in
1838 to describe a thick, leathery breast plate of cancer involving the chest and
abdominal wall.
7
Primary carcinoma en cuirasse is rare, presenting as extensive skin involvement in
the setting of untreated malignancy; secondary disease is more common, presenting
as a local chest wall recurrence after mastectomy, radiation, or chemotherapy.
8
In this case, carcinoma en cuirasse was caused by occult breast cancer.
The pathogenesis of carcinoma en cuirasse remains largely unknown. It is speculated
that pleiotrophin, an extracellular signaling molecule, acts as a multifunctional
tumor promoter leading to rapid tumor growth and progression to the scirrhous subtype
of invasive carcinoma.
9
Clinically, this carcinoma begins as scattered, firm, papulonodules overlying an
erythematous skin surface progressing to brawny hardness, which eventually coalesces
into a sclerodermoid plaque.7, 8 Histologically, there is extensive dermal fibrosis
with single filing of atypical malignant cells; tumors cells may be overlooked because
of similarity in appearance to fibroblasts.
10
Treatment options are limited. Because the tumor cells cause extensive reactive fibrosis
and decreased vascularity, chemotherapeutic agents may be unable to obtain tumoricidal
concentrations locally.8, 10 The goal is palliative; local irradiation, skin graft,
and nonsteroidal anti-inflammatory drug therapy have shown some success.
To our knowledge, this is the first reported case of carcinoma en cuirasse caused
by male breast cancer, and the fifth reported case of PLC in a man. Our case serves
to highlight the rapid progression of this rare malignancy and the challenges associated
with early detection, diagnosis, and treatment.