Rare skin appendage tumour on the right leg: a case of primary cutaneous cribriform carcinoma

Abstract

A woman in her 60s presented with a longstanding history of a purplish, fleshy and pedunculated nodule on the right shin on a background of bilateral lower limb lymphoedema. A shave biopsy with double curettage of the base of the lesion revealed a nodular tumour with hyperchromatic basaloid cells arranged in a cribriform pattern and encircling eosinophilic substance. Immunohistochemistry staining showed cells positive for pancytokeratin, low molecular weight keratin, BerEP4 and negative for cytokeratin 20. There were no clinical or radiological features of primary visceral malignancy. These histological and immunohistochemical features favour a diagnosis of primary cribriform carcinoma of the skin. This is a rare, indolent skin appendage tumour of presumed apocrine origin with no reported cases in the literature of metastasis or local recurrence after excision.

Background

Primary cribriform carcinoma is a rare skin appendage tumour with less than 50 cases reported worldwide. It can present clinically as a plaque or nodule without any distinctive features to help the clinician differentiate it from other skin lesions. Even though studies have not shown any definitive malignant potential of primary cribriform carcinoma, it is best treated with wide local excision and close patient follow-up as it is relatively rare.

Case presentation

A woman in her 60s presented with a history of a lesion over her right shin for 6–7 years. She had a possible infection at the site prior to the onset of the lesion and there was a lymphoedema to both lower legs, for which she was using compression hosiery. The lesion had remained unaltered over time, but 3–4 weeks prior to her presentation, it started to bleed and ooze serous fluid.

Her medical history included bilateral Charcot knees, osteopenia, diabetes, lymphoedema, hypertension and a lipoma on the right upper arm.

Clinical examination revealed a persistent, non-pitting oedema on both of her lower limbs up to her groin. She had a 15 mm purplish, fleshy and pedunculated nodule on the right shin.

Investigations

A shave excision with double curettage to the base of the lesion was arranged for diagnosis. Histology of the lesion showed a skin appendage tumour with a solid, ductal, cystic, cribriform and papillary architecture (figure 1). There were interconnected strands and nests of basaloid cells with prominent duct formation. There were basaloid cells arranged in a cribriform pattern encircling variably sized round spaces filled with bluish or eosinophilic substances. There were no pools of mucin seen in any field of the specimen (figure 2).

Figure 1.

Tumour showing a solid/ductal architecture (H&E staining, original magnification ×100).

Figure 2.

Higher magnification showing basaloid keratinocytes arranged in a cribriform pattern around eosinophilic substances (H&E staining, original magnification ×200).

Immunohistochemistry revealed that the lesional cells expressed pancytokeratins (AE1/AE3) and low molecular weight cytokeratins (CKs) (Cam5.2, CK7), BerEP4 and p63. The ducts were highlighted with epithelial membrane antigen (EMA) and some luminal borders expressed carcinoembryonic antigen (CEA) (figures 3 and 4). There was low mitotic activity with a mitotic rate of 2% and no areas of necrosis. Some of the cribriform areas expressed BCl2 and CD10. The lesional cells lacked a myoepithelial layer (smact, calponin and S100 were negative).

Figure 3.

Immunohistochemistry showing tumour cells positive for BerEP4 (original magnification ×400).

Figure 4.

Immunohistochemistry showing tumour cells positive for epithelial membrane antigen (original magnification ×100).

Differential diagnosis

The presence of the cribriform architecture in addition to the immunohistochemistry pattern of positive pancytokeratin in addition to BerEP4 favoured a diagnosis of primary cribriform carcinoma of the skin. The differential diagnoses considered at the time were cutaneous metastasis from visceral malignancies such as breast carcinoma, lung adenocarcinomas and non-mucinous ovarian adenocarcinoma; however, she did not have clinical or radiological evidence of any visceral malignancy. Other differentials considered included a primary mucinous carcinoma of the skin; however, no pools of mucin were seen on histology. Primary adenoid cystic carcinoma was excluded due to the absence of CD43 on immunocytochemistry. Adenoid cystic carcinoma was also excluded due to the lack of basaloid epithelial cells with more uniform nuclei surrounding the pseudolumina. The following markers were also negative: c-kit, CD43, CD15, CK20, which exclude other differential diagnoses like primary adenoid cystic carcinoma.

Treatment

She had Mohs micrographic surgery, one-stage excision with an 8 mm radial margin for re-excision of the scar, and the histology has been reported as showing no residual carcinoma in the skin and subcutaneous tissue. A whole-body CT scan and clinical examination did not reveal any evidence of visceral or breast malignancy, and ongoing reviews under the care of the dermatology team are in place.

Outcome and follow-up

After discussion at the specialist skin cancer multidisciplinary team, it was recommended that she had regular clinical surveillance follow-up for 5 years to monitor for local recurrence or distant metastasis.

Discussion

Primary cutaneous cribriform carcinoma (PCCC), also known as cribriform carcinoma of the skin, is a slow-growing, rare tumour of the skin’s appendages that is thought to have an apocrine origin. Only 42 histologically confirmed cases of PCCC were reported worldwide in a recent systematic review, published in 2021.¹ The first case was described in 1998. PCCC is more common in women, with a female-to-male ratio of 2:1 and a median age of 47 years at diagnosis. No recurrence or metastasis from a confirmed case of PCCC has been reported, even though its malignant potential is still unknown.²

Clinically, PCCC usually appears on the extremities of middle-aged individuals as a well-circumscribed dermal or subcutaneous nodule. The diagnosis relies mainly on histology and immunohistochemistry. Histologically, it is distinguished by nests of neoplastic cells that anastomose and form cribriform spaces, giving the lesion a sieve-like appearance. Most published cases of PCCC express positive immunohistochemistry staining for CK AE1/AE3, Cam5.2, MNF116 and CK7.³ In most cases, CEA and EMA are positive, demonstrating luminal differentiation.⁴ PCCCs do not express either gross cystic disease fluid protein 15, which is present in breast carcinomas; or CK20, which is present in tumours with a cribriform pattern in the prostate and salivary glands.^{4 5} Additionally significant is the absence of CK20 staining, which excludes Merkel cell carcinoma as a differential diagnosis. Consistent with the currently presented case, S100 staining has been reported to be negative in PCCC.^{4 5} In the literature, the primary differential diagnoses of PCCC include a cutaneous metastasis from a cribriform visceral carcinoma and primary cutaneous adenoid cystic carcinoma, hence the need to obtain a detailed history and perform a thorough examination in order to exclude the possibility of breast cancer or other visceral malignancies.¹ In terms of cell morphology, the presence of neurotropism and the deposition of basement membrane material distinguish PCCC from adenoid cystic carcinoma. The latter’s tumour cells are more uniform and basophilic. In addition to the deposition of basement membrane material and neurotropism, the latter is also frequently associated with infiltrative growth patterns, rare lymph node and lung metastases, and perineural infiltration.^{5 6}

Wide local excision or Mohs micrographic surgery is used to treat PCCC to ensure complete clearance of the tumour. When cutaneous cribriform carcinoma is diagnosed, clinicians must also maintain a high index of suspicion for breast carcinoma and metastasis from primary visceral malignancies and investigate these appropriately. As this is a rare skin appendage tumour and there is no literature on its malignant potential, follow-up for evidence of recurrence or metastasis has also been advised after a wide local excision with clear margins.³

Learning points.

• Clinicians need to remember that primary cribriform carcinoma presents as subcutaneous or dermal nodules on the extremities.

• Clinicians should also exclude cutaneous metastasis from primary visceral malignancies as the most important differential diagnosis of primary cribriform carcinoma.

• Patients with primary cribriform carcinoma need to be discussed at the skin cancer multidisciplinary team meeting and offered active surveillance as it is a rare skin appendage tumour.

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