Thyroid Transcription Factor-1 Is Expressed in Extrapulmonary Small Cell Carcinomas but Not in Other Extrapulmonary Neuroendocrine Tumors

Agoff, S. Nicholas; Lamps, Laura W.; Philip, Abraham T; Amin, Mahul B.; Schmidt, Rodney A.; True, Lawrence D.; Folpe, Andrew L.

doi:10.1038/modpathol.3880044

Cited by 316 publications

(193 citation statements)

References 16 publications

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“…Unlike LCNEC, MTC usually expresses calcitonin, TTF-1, and polyclonal carcinoembryonic antigen (CEA). Calcitonin expression should not be used in isolation as cases of calcitonin positive neuroendocrine carcinomas of the larynx have been reported [4,5,27], and, as noted previously, it is well known that a significant minority of nonpulmonary neuroendocrine carcinomas can express TTF-1 [25,28]. A laryngeal tumor as the presenting finding of MTC was reported by Sweeney in 1981 [29].…”

Section: Discussionmentioning

confidence: 89%

Large Cell Neuroendocrine Carcinoma of the Larynx: Definition of an Entity

Lewis

Spence

Chiosea

et al. 2010

Head and Neck Pathol

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Laryngeal atypical carcinoids (AC/moderatelydifferentiated neuroendocrine carcinoma) are associated with moderately aggressive clinical behavior; however, a subset of tumors classified as AC have much greater aggressive potential. These tumors fulfill the proposed diagnostic criteria for pulmonary large cell neuroendocrine carcinoma, albeit in the larynx. In the current WHO classification, laryngeal large cell neuroendocrine carcinomas (LCNEC) are classified as variants of AC, whereas pulmonary LCNEC are classified as poorly-differentiated neuroendocrine carcinomas. Reported outcomes for pulmonary tumors support the separate classification of LCNEC. Five and ten year survival rates for pulmonary AC are 61-73, and 35-59%, respectively, while the 5-year survival rate for pulmonary LCNEC is as low as 30%. By extension, we postulate that the biologic potential of laryngeal LCNEC is similar to that of small-cell carcinoma (poorly-differentiated neuroendocrine carcinoma), and as such, warrants reclassification. The files of Barnes Jewish Hospital/Washington University were searched for the term ''neuroendocrine'' and the anatomic subsite larynx. Neuroendocrine carcinoma cases were evaluated using the WHO definitions for pulmonary AC and LCNEC; small cell carcinoma was excluded. Cases were also solicited from the larger head and neck pathology community. A literature search was also performed for cases of laryngeal neuroendocrine carcinoma, and cases which could be clearly classified as LCNEC by this scheme were captured as well. Six new cases plus four reported cases were identified which fulfill the WHO criteria for pulmonary LCNEC (eight men and two women). Nine patients presented at stage IV and 88% died of disease (DOD), 75 and 100% of these at 2 and 3 years, respectively. Laryngeal LCNEC is a rare entity, distinct from AC. We recommend that laryngeal tumors fulfilling WHO criteria for pulmonary LCNEC not be classified as variants of AC, but as variants of small cell carcinoma (poorly-differentiated neuroendocrine carcinoma) as they are associated with poorer outcome.

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Section: Discussionmentioning

confidence: 89%

Large Cell Neuroendocrine Carcinoma of the Larynx: Definition of an Entity

Lewis

Spence

Chiosea

et al. 2010

Head and Neck Pathol

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“…Protein IHC has additional variation in antibody retrieval methods and antibody clone differences, as well as wide variation in techniques and controls used between labs; all these factors can all affect the rate of false positive and false negative IHC results. [68][69][70][71][72][73][74] In addition, selection of specific IHC markers and the interpretation of the protein expression patterns can be subjective and is dependent on the individual pathologist.…”

Section: Discussionmentioning

confidence: 99%

A 92-gene cancer classifier predicts the site of origin for neuroendocrine tumors

Kerr

Schnabel²,

Sullivan

et al. 2014

Modern Pathology

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A diagnosis of neuroendocrine carcinoma is often morphologically straight-forward; however, the tumor site of origin may remain elusive in a metastatic presentation. Neuroendocrine tumor subtyping has important implications for staging and patient management. In this study, the novel use and performance of a 92-gene molecular cancer classifier for determination of the site of tumor origin are described in a series of 75 neuroendocrine tumors (44 metastatic, 31 primary; gastrointestinal (n ¼ 12), pulmonary (n ¼ 22), Merkel cell (n ¼ 10), pancreatic (n ¼ 10), pheochromocytoma (n ¼ 10), and medullary thyroid carcinoma (n ¼ 11)). Formalinfixed, paraffin-embedded samples passing multicenter pathologist adjudication were blinded and tested by a 92-gene molecular assay that predicts tumor type/subtype based upon relative quantitative PCR expression measurements for 87 tumor-related and 5 reference genes.

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“…2,4,16 Extrapulmonary small-cell carcinomas may also express TTF-1. 18,19 For these reasons, staining results must be interpreted in the context of tumor cell morphology and clinical and radiographic information.…”

Section: Discussionmentioning

confidence: 99%

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

2006

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In histology and cell block sections, antibodies to thyroid transcription factor-1 (TTF-1) and p63 have been demonstrated to be useful markers for distinguishing between small-cell lung carcinoma and poorly differentiated pulmonary squamous cell carcinoma. In this study, we assessed the utility of TTF-1 and p63, as an antibody panel, for differentiating between these two neoplasms in previously Papanicolaou (Pap)-stained cytologic smears and cytospin slides. Twenty-six lung carcinomas (13 small-cell lung carcinomas, 13 poorly differentiated pulmonary squamous cell carcinomas) were evaluated. One or two previously 95% ethanol-fixed, Pap-stained smears or cytospin slides were selected from each case. The cytologic material from these slides was transferred to positively charged slides. Unstained recuts were obtained from the corresponding histologic specimens or cell blocks. Immunohistochemical staining for TTF-1 and p63 was performed on the paired samples from each tumor. All (13/13) small-cell lung carcinomas were negative for p63 and 92% (12/13) were positive for TTF-1. Conversely, all (13/13) poorly differentiated pulmonary squamous cell carcinomas expressed p63 and did not express TTF-1. Immunoreactivity for p63 was also noted in bronchial reserve cells and metaplastic squamous cells. The immunostaining results obtained from the cytology slides were concordant with those of the histology or cell block sections in all cases. The results of this study show that TTF-1 and p63 immunostaining can be successfully applied to previously Pap-stained cytologic material, as an antibody panel, to facilitate pathologic differentiation between small-cell lung carcinomas and poorly differentiated pulmonary squamous cell carcinomas. p63 immunostaining, however, must be interpreted in conjunction with cytomorphology to distinguish between poorly differentiated pulmonary squamous cell carcinomas and benign cellular constituents of the lung.

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Thyroid Transcription Factor-1 Is Expressed in Extrapulmonary Small Cell Carcinomas but Not in Other Extrapulmonary Neuroendocrine Tumors

Cited by 316 publications

References 16 publications

Large Cell Neuroendocrine Carcinoma of the Larynx: Definition of an Entity

Large Cell Neuroendocrine Carcinoma of the Larynx: Definition of an Entity

A 92-gene cancer classifier predicts the site of origin for neuroendocrine tumors

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

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