PAX8 Positivity, Abnormal p53 Expression, and p16 Negativity in a Primary Endometrial Squamous Cell Carcinoma: A Case Report and Review of the Literature

Abstract

Primary endometrial squamous cell carcinoma (PESCC) is a rare entity. As the clinicopathologic features and the immunophenotype have not been completely defined yet, here we report our experience and review of the literature on this topic. A 73-yr-old nulliparous woman presented with pelvic pain and vaginal bleeding. Endometrial biopsy showed a carcinoma with squamous differentiation infiltrating the myometrium. Total hysterectomy with bilateral salpingo-oophorectomy and selective pelvic lymphadenectomy was performed. Definitive diagnosis was squamous carcinoma of the endometrium, with one lymph node metastasis (stage IIIC1). Immunohistochemistry evidenced immunoreactivity of the tumor cells for cytokeratin 5, p63, cytokeratin 7, PAX8, PTEN, and cyclin D1, aberrant p53 overexpression, and Ki-67 reactivity in ~70% of the tumor cells. Estrogen and progesterone receptor, PAX2, WT1, and p16 were negative. Our case was the first PAX8-positive PESCC in the literature, underlining the Mullerian system origin of this neoplasm. Abnormal p53 expression of this case confirmed its role in the pathogenesis of PESCC. Further studies on a large number of cases are needed to better understand the pathologic features and the immunophenotype of PESCC.

Molecular Analysis of HPV-independent Primary Endometrial Squamous Cell Carcinoma Reveals TP53 and CDKN2A Comutations

“…This is similar to the results of this study, where ER and PR were negative in all cases. An aberrant p53 expression pattern was identified in at least 4 of 21 (19%) reported cases 5,7–10,18. Before the recommendations for p53 immunohistochemical reporting in endometrial carcinomas were established,22,23 some reported HPV-independent PESCCs were described as p53 “positive” or “negative.” However, it is challenging to determine if cases reported as “positive” represent an aberrant/mutation-type pattern with diffuse nuclear overexpression, an aberrant cytoplasmic staining pattern, or a normal/wild-type pattern when the specific details of p53 immunostaining interpretation are not provided, as is the situation in 2 of 21 (10%) prior cases.…”

“…A total of 28 cases was identified in 14 studies (Table 4). 4,5,[7][8][9][10][11][12][13][14][15][16][17][18] The median age at diagnosis was 62 years, which is slightly younger than the women in our study (mean and median, 78 y). The majority of cases were negative for ER and PR in 19/23 (82.6%) and 19/22 (86.4%) cases, respectively.…”

“…An aberrant p53 expression pattern was identified in at least 4 of 21 (19%) reported cases. 5,[7][8][9][10]18 Before the recommendations for p53 immunohistochemical reporting in endometrial carcinomas were established, 22,23 some reported HPVindependent PESCCs were described as p53 "positive" or "negative." However, it is challenging to determine if cases reported as "positive" represent an aberrant/mutation-type pattern with diffuse nuclear overexpression, an aberrant The clinicopathologic and molecular results reported herein are similar to what has been described in SCCs arising in other locations in the lower gynecologic tract.…”

“…For HPV ISH, specimens were processed as previously described using the Leica Bond III autostainer (Leica Biosystem, Buffalo Grove, IL). 25 The RNA ISH used RNAscope probes as follows: high-risk cocktail including HPV types 16,18,26,31,33,35,39,45,51,52,53,56,58,59, 66, 68, 73, 82 (HPV-HR18, Cat# 312598; Advanced Cell Diagnostics, Hayward, CA), HPV-16 (HPV-16, Cat# 311528), HPV-18 (HPV-18, Cat# 311538), low-risk cocktail including HPV types 6 and 11 (HPV6/11, Cat# 415218). RNA ISH was considered positive if punctate brown signals were present in the cytoplasm and/or nucleus.…”

“…The pathogenesis of PESCC is not well understood, and both human papillomavirus (HPV)-associated [4][5][6] and HPV-independent 4,5,[7][8][9][10][11][12][13][14][15][16][17][18] tumors have been described. For HPV-independent tumors, nulliparity, pyometra, and ichthyosis uteri have been implicated as associated conditions.…”