Distinction of pulmonary small cell carcinoma from poorly differentiated squamous cell carcinoma: an immunohistochemical approach

Abstract

Accurate morphologic distinction between small cell carcinoma and poorly differentiated squamous cell carcinoma has critical therapeutic significance, but can be limited by crush artifact, tumor necrosis, limited tumor representation, and overlapping morphologic features. We evaluated a panel of antibodies for their efficacy in distinguishing between these neoplasms. Formalin-fixed paraffin-embedded tissue sections of small cell carcinomas and poorly differentiated squamous cell carcinomas underwent immunohistochemical staining with antibodies to thyroid transcription factor-1, p63, high molecular weight keratin, and p16(INK4A). Of 28 small cell carcinomas, 26 (93%) small cell carcinomas showed diffuse moderate or strong staining for thyroid transcription factor-1 with no staining for high molecular weight keratin and p63. In contrast, 27/28 (96%) poorly differentiated squamous cell carcinomas manifested opposite immunoreactivities, with diffuse moderate or strong staining for high molecular weight keratin and p63, and no or minimal staining for thyroid transcription factor-1. In two additional cases originally interpreted as small cell carcinoma, high molecular weight keratin highlighted small numbers of neoplastic large cells, leading to reclassification as combined small cell and nonsmall cell carcinomas. p16(INK4A) expression varied widely in poorly differentiated squamous cell carcinomas, but was consistently moderate or strong and diffuse in small cell carcinomas, and proved helpful in the two thyroid transcription factor-1-negative small cell carcinomas. This study demonstrates that a panel consisting of antibodies to thyroid transcription factor-1, p63, high molecular weight keratin, and p16(INK4A) is highly effective for distinguishing between small cell carcinoma and poorly differentiated squamous cell carcinoma. This panel also facilitates diagnosis of combined small cell and non-small cell carcinomas.

The diagnostic utility of immunohistochemistry in distinguishing between epithelioid mesotheliomas and squamous carcinomas of the lung: a comparative study

“…[68][69][70] Subsequent investigations using the 8G7G3/1 monoclonal antibody, however, have shown that TTF-1 expression is usually absent in these tumors. 47,[71][72][73][74][75] In the present investigation, none of the squamous carcinomas of the lung or the mesotheliomas exhibited TTF-1 positivity. While these findings indicate that TTF-1 immunostaining is not useful in discriminating between these malignancies, it may have some utility in distinguishing squamous carcinomas from lung adenocarcinomas since this marker is often expressed in the latter tumors.…”

“…These results are in agreement with those previously reported in the literature in which expression for this protein occurred in 80-100% of the squamous carcinomas of the lung. [43][44][45][46][47] Only two studies, with relatively few cases, have investigated the expression of p63 in mesotheliomas and in neither did any of the cases exhibit positivity for this protein. 44,48 In the present study, two (7%) of the mesotheliomas expressed p63.…”

Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis

“…p63 plays a role in stem cell commitment in squamous epithelium. 37 Some reported that p63 was expressed in pulmonary squamous cell carcinoma but not in small cell carcinomas, 37,38 whereas others reported that large cell neuroendocrine carcinoma and small cell carcinoma had p63 expression. 39,40 The reported differences of frequency of p63 expression in small cell carcinoma may be due to different identification methods for positive cells.…”

TTF-1 and p63 for distinguishing pulmonary small-cell carcinoma from poorly differentiated squamous cell carcinoma in previously pap-stained cytologic material

“…5,6 The combined use of TTF-1 and p63 antibodies on tissue and cell block sections showed that the TTF-1 þ /p63À phenotype is present in 87-94% of small-cell lung carcinomas, and the p63 þ /TTF-1À phenotype in 96-100% of poorly differentiated pulmonary squamous cell carcinomas. [7][8][9] The utility of TTF-1 and p63 immunostaining on 95% ethanol-fixed cytologic smears has rarely been reported and has been limited to a single antibody in each study. [10][11][12] TTF-1 or p63, as a single marker, may play a limited role in differential diagnosis between small-cell lung carcinoma and poorly differentiated pulmonary squamous cell carcinoma.…”

“…5,6 TTF-1 and p63 immunostaining in histologic and cell block material is a valuable aid for separating small-cell lung carcinomas and poorly differentiated pulmonary squamous cell carcinomas. [7][8][9] Recently, we reported that TTF-1 immunostaining can be successfully used on previously Papanicolaou (Pap)-stained cytologic material, 10,11 and one other study demonstrated that p63 immunostaining can be performed to identify pulmonary squamous cell carcinomas on destained bronchoscopic cytologic specimens. 12 However, these studies revealed some diagnostic limitations.…”