Squamous cell carcinoma is one of the most common cutaneous cancers; however, primary squamous cell carcinoma of the nipple is extremely rare. Among the few reported cases, the majority have occurred in older women with rare cases seen in younger women and male patients. Our patient presented with an exophytic mass of the right nipple while pregnant. A superficial biopsy was reviewed at an outside institution and then at our institution and diagnosed as squamous papilloma and then as hyperkeratosis of the nipple, respectively. The subsequent excisional biopsy revealed multiple nests of tumor cells extending into the dermis with associated chronic inflammatory infiltrate, and the lesion was diagnosed as a primary invasive squamous cell carcinoma of the nipple. Following that, a wide local excision of the excision site and sampling of the regional lymph nodes were negative for carcinoma. Due to the rarity of this diagnosis, it is not known whether prognosis and response to therapy differ from cutaneous squamous cell carcinoma at other sites. Therefore, risk stratification and therapy have been based on those for cutaneous squamous cell carcinoma.
Primary squamous cell carcinoma of the nipple is an extremely rare condition, with only nine cases reported in the English literature [
The patient is a 29-year-old pregnant female, who originally presented with a small nodule on the tip of her right nipple, at approximately 28 weeks of gestation. The lesion increased in size over the next few weeks and showed no improvement with a 2-week course of antibiotic treatment (Keflex). Due to the progressive increase in the size of the lesion, the patient was referred to a general surgeon and underwent an incisional biopsy. As seen in Figures
Low power view of the initial biopsy (HE, 4x).
Initial biopsy showing acanthosis, hyperkeratosis, and keratotic plugging (HE, 10x).
The patient delivered a healthy infant but was unable to nurse on the right side due to sloughing of the nipple skin and pain. In addition, the lesion continued to increase in size. On physical examination at our institution, a soft, exophytic mass of the right nipple was noted. The areola was uninvolved. No other abnormalities in either breast and no axillary lymphadenopathy were detected. A mammogram was performed and revealed no masses, calcifications, or sites of architectural distortion within the breast parenchyma. The radiologist noted that, due to the heterogeneously dense breast composition, small masses could be obscured and a targeted ultrasound was performed. The ultrasound revealed an enlarged right nipple, approximately 1.7 cm in diameter with a hypervascular nipple mass. The subareolar ducts were normal in size, without evidence of an intraductal mass. Although the previous sample had been interpreted as benign, the biopsy was superficial, and, given the progressive increase in size, excision of the lesion was recommended. The patient underwent excisional biopsy of the right nipple lesion and, on gross examination, the nipple showed an ill-defined soft yellow/white friable verrucous mass measuring 2.4 × 1.6 × 1.1 cm. Histology revealed an exuberant squamous proliferation with exophytic growth pattern, marked hyperkeratosis, acanthosis, and collarettes at the periphery, all features suggestive of a keratoacanthoma (Figure
Whole slide image of the squamous cell carcinoma showing the keratoacanthoma-like features (HE). The box indicates the area shown in Figure
Area extracted from the whole slide image showing nests of invasion and surrounding inflammation (HE).
The distinction between keratoacanthoma and squamous cell carcinoma remains difficult and controversial. Features of our lesion that favor invasive squamous cell carcinoma include prominent nuclear atypia, mitotic figures (Figure
Area extracted from the whole slide image showing cytologic detail and mitotic figure (HE).
Area extracted from the whole slide image showing desmoplastic response (HE).
Area extracted from the whole slide image showing extension of tumor deep to the sebaceous glands and a lactiferous duct (HE).
Positive nuclear immunostaining for p53 in invasive nests (p53, 20x).
Subsequently, the patient underwent a wide local excision with regional lymph node dissection. The entire excision specimen was submitted for histopathologic evaluation and was negative for carcinoma. Regional lymph nodes were also negative for metastatic disease. The patient has no evidence of recurrence after 15 months.
Squamous cell carcinoma is one of the most common cutaneous cancers and causes significant morbidity, particularly in elderly patients [
The previous case reports are summarized in Table
Case reports, squamous cell carcinoma of the nipple and areola.
Patient | Risk factors | Carcinoma | Therapy | Outcome | |
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Venkataseshan et al. [ |
84 y.o. F | Not known | In situ | WLE | DF × 30 months |
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Sharma and Iyer [ |
41 y.o. M | HIV disease | In situ |
Mastectomy, SLN | DF × 3 years |
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Brookes et al. [ |
71 y.o. F | XRT | In situ | Photodynamic | Residual × 2, cryotherapy |
69 y.o. F | Not known | Invasive | WLE | Recurrence at 3 months, repeat excision | |
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Loveland-Jones et al. [ |
66 y.o. F | XRT | Invasive | WLE | Not reported |
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Hosaka et al. [ |
73 y.o. F | Not known | Superficially invasive (<1 mm) |
Mastectomy, ALND | DF × 5 years |
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Upasham et al. [ |
87 y.o. F | Not known | Invasive |
Mod. rad. mastectomy | Not reported |
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Sofos et al. [ |
34 y.o. F | Not known | Invasive | WLE | DF × 12 months |
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King and Kremer [ |
62 y.o. M | Sun exposure × 10 years | Invasive with NE differentiation | WLE | Not reported |
XRT = radiation therapy; LN = lymph node; SLN = sentinel lymph node; ALND = axillary lymph node dissection; WLE = wide local excision; DF = disease-free.
In the previously reported cases of squamous cell carcinoma of the nipple, two patients presented with an exophytic mass [
Nevoid hyperkeratosis is a rare lesion and, in one small series [
In the context of our case, pregnancy associated hyperkeratosis was a consideration based on the initial biopsy. In one case series of pregnancy associated hyperkeratosis, most of the lesions were yellow to tan or mildly pigmented, hyperkeratotic, and/or warty papules on clinical examination [
In general, invasive squamous cell carcinoma of the nipple is easily distinguishable from hyperkeratosis of the nipple. In this case, the initial diagnosis of a hyperkeratotic rather than invasive entity was due to the superficial nature of the biopsy. As is evident in comparing Figures
Superficial aspect of resected specimen (HE, 20x).
In our patient, histologic examination failed to reveal lymphovascular or perineural invasion and the carcinoma was staged based on the American Joint Committee on Cancer (AJCC) staging for cutaneous squamous cell carcinoma [
Eight of the previously reported patients with squamous cell carcinoma were treated with surgery [
Primary squamous cell carcinoma of the nipple is a very rare diagnosis. Occurrence of this lesion in a young pregnant woman with no known risk factors for cutaneous cancer made this case all the more challenging. This example highlights the importance of considering rare entities in the differential diagnosis of a hyperkeratotic lesion of the nipple. We hope that our report of a primary squamous cell carcinoma of the nipple in a young pregnant woman will help further understanding of this rare entity.
The authors declare that there is no conflict of interests regarding the publication of this paper.