Value of p63 and podoplanin (D2‐40) immunoreactivity in the distinction between primary cutaneous tumors and adenocarcinomas metastatic to the skin: a clinicopathologic and immunohistochemical study of 79 cases

Abstract

The distinction of metastatic carcinomas to the skin from poorly differentiated primary cutaneous carcinomas and sometimes primary benign adnexal tumors can pose a significant diagnostic challenge. The purpose of this study was to evaluate the role of p63 and podoplanin (D2-40) immunoreactivity for separating primary skin tumors vs. cutaneous metastases of carcinomas from internal organs. Thirty seven primary tumors and 42 cutaneous metastatic adenocarcinomas were evaluated. The 37 primary cutaneous tumors included 14 cases of benign adnexal tumors, 9 malignant skin adnexal neoplasms, and 14 primary squamous and basal cell carcinomas. The 42 metastatic adenocarcinomas all corresponded to metastases from patients with a well-documented history of a primary tumor at another location. We found variable positivity with podoplanin in all primary cutaneous neoplasms including spiradenoma (6/6), hidradenoma (2/4), cylindroma (3/3), desmoplastic trichilemmoma (1/1), poorly differentiated squamous cell carcinoma (4/4), sebaceous carcinoma (1/1), basal cell carcinoma (4/10), trichilemmal carcinoma (2/2), eccrine carcinoma (3/3), microcystic adnexal carcinoma (1/1), adnexal carcinoma NOS (1/1), and porocarcinoma (1/1). In contrast, all metastatic carcinomas were negative (0/42) for podoplanin. In regards to p63, all cases of primary cutaneous tumors were positive for p63 (37/37); in contrast, all cutaneous metastatic carcinomas were negative (0/42). Sensitivity, specificity, and positive and negative predictive values of podoplanin and p63 immunoreactivity to separate primary skin neoplasms from metastatic carcinomas were 78.4, 100.0, 100.0 and 84.0% for podoplanin, respectively, and 100.0, 100.0, 100.0 and 100.0% for p63, respectively. The differences in p63 and podoplanin immunohistochemical expression between primary skin tumors and metastatic carcinomas to the skin were statistically significant (p < 0, 0001). The results of our study suggest that the combined expression of p63 and podoplanin are a useful adjunct for the diagnosis of skin tumors in the clinical setting of a questionable metastasis and may be relatively specific for distinguishing primary skin tumors from metastatic carcinomas to the skin.

Podoplanin expression correlates with sentinel lymph node metastasis in early squamous cell carcinomas of the oral cavity and oropharynx

“…[15][16][17][18][19][20][21] These findings suggest that podoplanin plays a role in the progression of epithelial cancer. However, the exact molecular function of cancer cell-expressed podoplanin is currently studied.…”

Inmunohistoquímica en dermatopatología: revisión de los anticuerpos utilizados con mayor frecuencia (parte i)

“…Se utiliza también para demostrar la naturaleza linfática de los vasos conteniendo células neoplásicas en su luz en émbolos tumorales, tanto de tumores cutáneos primarios como de metástasis cutáneas. También es útil para diferenciar histopatológicamente neoplasias cutáneas primarias, especialmente adenocarcinomas anexiales, de metástasis cutáneas de adenocarcinomas de vísceras internas, ya que la podoplanina se expresa en las células neoplásicas de los primeros, pero no de los segundos 47,48 . Por último, estudios recientes han propuesto utilizar este marcador junto con otros marcadores endoteliales, como Lyve-1 y CD31 en la predicción de metástasis en el ganglio centinela de melanomas, valorando la invasión intralinfática del tumor primario 49 .…”

My Journey into the World of Salivary Gland Sebaceous Neoplasms

“…In a recent paper, p63 stained all sebaceous and NSLs, 11 and 7, respectfully [21], while a separate study found that all 16 metastatic renal cell carcinomas were negative for this antibody [55]. In addition, three primary sebaceous carcinomas of the skin in several recent studies also stained with p63 [54,56,57]. Therefore, it appears that a positive p63 stain likely eliminates the possibility of a metastasis from a renal primary.…”