Painful, bleeding fingertip papule.

A 66-year-old man presented with a 3-month history of a painful and bleeding fingertip papule that had temporarily improved after silver nitrate application. Pertinent history included stage IV clear cell renal cell carcinoma (ccRCC) treated with radical nephrectomy and adjuvant ipilimumab/nivolumab. Recent imaging confirmed continued regression of metastases, and the patient was clinically doing well. Examination demonstrated a violaceous and hyperkeratotic papule (Fig 1). Biopsy revealed a dermally based, lobulated, eosinophilic epithelioid cell population with extravasated red blood cells (Fig 2). Immunohistochemistry was negative for CD31, CK7, and CK20 and positive for AE1/AE3, AMACR, PAX8, and CD10 within the epithelioid cell population.

Fig 1

Fig 2

Question 1: What is the most likely diagnosis?

Poroma

Squamous cell carcinoma

Wart

Pyogenic granuloma

ccRCC metastasis

Answers:

Poroma – Incorrect. Poromas can have a strikingly similar presentation clinically. However, histologically, they are different in appearance, being composed of sheets and nodules of cuboidal epithelial cells with scattered small clear spaces representing duct formation. In addition, vascular proliferation is not often observed.

Squamous cell carcinoma – Incorrect. Squamous cell carcinomas can and do occur on the digits and can have a similar clinical appearance. However, histopathologically, they are composed of atypical keratinocytes, which invade into the dermis, often with desmoplastic tumor response.

Wart – Incorrect. Clinically, warts appear as hyperkeratotic papules with small, thrombosed capillaries and could resemble this patient’s lesion. However, histologically, warts are characterized by acanthosis, hypergranulosis, and hyperkeratosis of the epidermis, and koilocytosis of keratinocytes can be observed in the upper granular layer.

Pyogenic granuloma – Incorrect. Pyogenic granulomas are typically located on the head/neck and oral mucosa, with a predilection for children and pregnant patients. Although they can also occur on the hands, they are histologically very different in appearance on high-power evaluation. Histologically, lobules of capillaries would be seen in a pyogenic granuloma; cytologically, atypical epithelioid cells would not be present. In addition, pyogenic granulomas have a vastly different immunoprofile from that of metastatic renal cell carcinoma (RCC).

ccRCC metastasis – Correct. This question requires the interpretation of both the clinical history and histologic description. The suspicion for cutaneous RCC is often low, and biopsy is usually performed to rule out another vascular entity, including the following benign lesions: pyogenic granuloma, poroma, and glomus tumors. Typically, ccRCC will contain diffuse cells with clear cytoplasm arranged in a trabecular pattern with prominent vasculature compared with the eosinophilic and papillary arranged cells of papillary renal cell carcinoma (pRCC). However, it is not uncommon for metastatic lesions of ccRCC to show a variety of histologic features, including cells with eosinophilic cytoplasm.

Question 2: Which of the following would be the expected immunohistochemical staining of ccRCC?

AE1/AE3+, AMACR+, CK7+, PAX8+

CD10+, AMACR−, CK7−, PAX8+

AMACR−, CK7+, CD10−, PAX8+

AE1/AE3−, AMACR−, CK7+, PAX8−

Vimentin-negative, AE1/AE3+, CK7+, PAX8−

Answers:

AE1/AE3+, AMACR+, CK7+, PAX8+ – Incorrect. This immunohistochemical profile is typical of pRCC. Although both pRCC and ccRCC are positive for AE1/AE3 and PAX8, the presence of CK7 and AMACR supports papillary type over clear cell type.

CD10+, AMACR−, CK7−, PAX8+ – Correct. The absence of AMACR and CK7 support clear cell origin., The presence of CD10 is indicative of pRCC or ccRCC origin.

AMACR−, CK7+, CD10−, PAX8+ – Incorrect. This immunohistochemical profile is most consistent with clear cell papillary RCC, given the absence of CD10 and AMACR and presence of CK7.

AE1/AE3−, AMACR−, CK7+, PAX8− – Incorrect. The presence of CK7 is not consistent with ccRCC.

Vimentin-negative, AE1/AE3+, CK7+, PAX8− – Incorrect. Both pRCC and ccRCC are of epithelial lineage and thus are classically positive for AE1/AE3. Although not performed in this case, it should be noted that staining with vimentin (a stain commonly believed as mesenchymal and historically used for sarcoma) is positive in ccRCC. Renal tumors that are associated with BAP1 mutation will also show constituent loss of BAP1 staining by immunohistochemistry.

Question 3: Which is the most commonly reported site of cutaneous ccRCC metastasis?

Back

Chest

Extremity

Face

Scalp

Answers:

Back – Incorrect. The back is a less common site for cutaneous metastasis of RCC.

Chest – Incorrect. The head and chest are the 2 most frequent sites of RCC metastasis, with the former being more common than the latter.

Extremity – Incorrect. Metastasis affecting the hand is reported to occur in 0.1% of RCC cases. The majority of acrometastases from RCC involve the bone. Cutaneous metastasis to the finger with no bone involvement (as seen in our case) is extremely rare. We found only 2 case reports describing cutaneous RCC metastasis to the finger without bone involvement.,

Face – Incorrect. The head, in general, is the most common site of cutaneous metastasis of RCC; however, the scalp specifically is a more common site than the face.

Scalp – Correct. The classic presentation of cutaneous RCC metastasis is a single nodule with blue, purple, or black-brown pigmentation affecting the scalp; however, the presentation can be variable, with even multiple nodules or plaques being observed. It is estimated that only 1.3% to 3% of RCCs will have a cutaneous metastasis. RCCs develop unpredictable metastases due to their propensity to be angioinvasive, and this vascular prominence underlies the theory that the majority of ccRCCs present on the scalp.

Conflicts of interest

None disclosed.