Use of p40 and p63 immunohistochemistry and human papillomavirus testing as ancillary tools for the recognition of head and neck sarcomatoid carcinoma and its distinction from benign and malignant mesenchymal processes

Abstract

Sarcomatoid carcinoma (SC) is a variant of head and neck squamous cell carcinoma characterized by a prominent and sometimes exclusive spindle cell component. Distinction from a sarcoma or reactive stroma can be problematic, particularly in cases in which the conventional component is not obvious. The value of immunohistochemistry is limited because of the loss of cytokeratin expression in a sizable percentage of cases. Staining for p63 can enhance detection of epithelial differentiation, but its usefulness is offset by expression in various soft tissue proliferations. Staining for p40--a squamous-specific isoform of p63--could potentially improve diagnostic accuracy. Immunohistochemistry for pancytokeratin, p63, and p40 was performed on 37 head and neck SCs, 201 soft tissue neoplasms, and 40 reactive stromal proliferations. The SCs were also stained for p16 in the event that some of the tumors were human papillomavirus (HPV) related. HPV in situ hybridization was performed on p16-positive cases. Twenty-three of 37 (62%) SCs were positive for pancytokeratin, 23 of 37 (62%) were positive for p63, and 20 of 37 (54%) were positive for p40. Compared with p63, p40 staining was less likely to be observed in soft tissue tumors (5% vs. 30%) and reactive stromal proliferations (0% vs. 30%). HPV16 was detected in 3 of 10 (30%) SCs of the oropharynx but in none of the nonoropharyngeal SCs. p40 staining does not improve the sensitivity for diagnosing SC, but it does diminish the risk of misdiagnosing a sarcoma or reactive stroma as SC. The presence of a sarcomatoid variant of HPV-related oropharyngeal cancer points to HPV testing as a useful diagnostic tool for atypical spindle cell proliferations of the oropharynx.

FIGURE 1

Sarcomatoid carcinoma. All of the sarcomatoid carcinomas included in the study were biphasic, consisting of an epithelial component (bottom left) in addition to a spindle cell component (A). This sarcomatoid carcinoma was positive in both areas for pancytokeratin (B), p63 (C), and p40 (D).

FIGURE 2

p40 and p63 staining in soft tissue tumors. These cases of leiomyosarcoma (A–C) and low-grade fibromyxoid sarcoma (D–F) were negative for p40 (B and E) but diffusely positive for p63 (D and F).

FIGURE 3

P63 staining of reactive stromal proliferations. In this example of atypical fibroblasts after radiation therapy (A), p63 was focally positive (B).

FIGURE 4

HPV-related sarcomatoid carcinoma. This example of sarcomatoid carcinoma (A) exhibited pancytokeratin staining in the conventional epithelial component but not in the spindle cell component (B). P16 staining (C) and HPV16 in situ hybridization signals (D) were present in both components.