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 HPVrelated oropharyngeal cancer points to HPV testing as a useful diagnostic tool for atypical spindle cell proliferations of the oropharynx.

Polymorphous Low Grade Adenocarcinoma has a Consistent p63+/p40− Immunophenotype that Helps Distinguish it from Adenoid Cystic Carcinoma and Cellular Pleomorphic Adenoma

“…Similar aberrant p63 immunolabeling has been seen in lung adenocarcinomas, soft tissue neoplasms, and lymphomas [27][28][29][30]. Recently, the antibody to p40, an isotype of p63, has emerged as a more specific marker of basal and myoepithelial cell differentiation [29][30][31][32]. Consequently, it is possible that p40 might also prove more useful than p63 for differentiating PLGA from adenoid cystic carcinoma and pleomorphic adenoma.…”

“…As such, the p63 staining in PLGAs appears likely to represent aberrant expression of the TAp63 isoform similar to that seen in lung adenocarcinomas, soft tissue tumors, and lymphomas, raising the possibility that a more myoepithelial-specific antibody may be able to distinguish these lesions. The antibody p40, specific for the DNp63 isotype of p63, has previously proven more specific for squamous and myoepithelial differentiation in tumors of other anatomic sites [29][30][31][32].…”

“…However, p63 has proven surprisingly unhelpful in distinguishing between PLGA, adenoid cystic carcinoma, and pleomorphic adenoma, as it often shows strong and diffuse positivity in PLGA despite its lack of myoepithelial differentiation [23,25,26]. Similar aberrant p63 immunolabeling has been seen in lung adenocarcinomas, soft tissue neoplasms, and lymphomas [27][28][29][30]. Recently, the antibody to p40, an isotype of p63, has emerged as a more specific marker of basal and myoepithelial cell differentiation [29][30][31][32].…”

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Oropharynx

“…It also includes, as recently described in small patient series, the presence of ciliated tumor cells "ciliated adenosquamous carcinoma". Although the number of reported cases of these variant forms is limited, the best available data suggests that patients with transcriptionally-active HPV have clinical outcomes that are similar to HPV-positive OPSCC with typical morphology [11][12][13][14][15][16][17][18][19][20][21].…”

Rhabdomyoblastic Differentiation in Head and Neck Malignancies Other Than Rhabdomyosarcoma

“…However it should be emphasized that true RMS may express cytokeratins in up to 7 % of cases [21]. Even the newer squamous marker p63 can be positive in RMS, although all cases reported so far have been negative for p40, the more squamous-specific isoform of p63 [56,57]. Further complicating the distinction from RMS or other sarcomas is that up to a third of sarcomatoid carcinomas are monophasic spindle cell neoplasms, and the sarcomatoid components of up to 74 % of sarcomatoid carcinomas are completely negative for epithelial markers [40,42,46,47,58].…”