Elsevier

Human Pathology

Volume 35, Issue 7, July 2004, Pages 825-831
Human Pathology

Original contribution
TTF-1 expression is specific for lung primary in typical and atypical carcinoids: TTF-1-positive carcinoids are predominantly in peripheral location

Presented in part at the 92nd annual meeting of the United States and Canadian Academy of Pathology, Washington, DC, March 22–28, 2003.
https://doi.org/10.1016/j.humpath.2004.02.016Get rights and content

Abstract

Thyroid transcription factor (TTF)-1 expression in neuroendocrine tumors (NETs) has not been studied as widely as that in non-NETs, with the exception of small cell carcinomas, in which TTF-1 is highly sensitive but not specific for a primary lung tumor. The reported incidence of TTF-1 expression in pulmonary carcinoids has also been highly variable in the literature. To evaluate the expression of TTF-1 in NETs and potential value of TTF-1 in distinguishing pulmonary NETs from those of extrapulmonary origin, we performed an immunohistochemical study by using semiquantitative analysis on formalin-fixed, paraffin-embedded sections from 111 NETs, including 80 pulmonary (11 carcinoid tumorlets [TLs] or foci of neuroendocrine cell hyperplasia [NEH], 36 typical carcinoids [TCs], 17 atypical carcinoids [ACs], 16 large cell neuroendocrine carcinomas [LCNECs]), 13 thymic (3 TCs, 8 ACs, 2 LCNECs), 17 gastrointestinal or pancreatic (13 TCs, 4 ACs), and 1 ovarian (LCNEC). Pulmonary carcinoids were subdivided into those with central and those with peripheral location. TTF-1 positivity was seen exclusively in pulmonary NETs and was significantly higher in NEH or TLs (72.7%) than in TCs (27.8%), ACs (29.4%), and LCNECs (37.5%; P = 0.03). All extrapulmonary NETs were uniformly negative for TTF-1 staining. Interestingly, 12 of 14 TTF-1-positive pulmonary TCs and ACs had a peripheral location with spindle cell morphology, as did all cases of TL, a purported precursor of peripheral carcinoids. In conclusion, TTF-1 expression was 100% specific, though not so sensitive, for the lung primary in TCs and ACs and possibly also in LCNECs. Prevalent TTF-1 positivity in TLs and peripheral carcinoids suggest that they may be histogenetically distinct from the central carcinoids, which are typically composed of TTF-1-negative, more rounded cells.

Section snippets

Case selection and classification

All pulmonary and extrapulmonary NETs (excluding small cell carcinomas) were identified from the surgical pathology files during the period of 1994 to 2002 at UCSD Medical Center, San Diego, CA. Additional cases of pulmonary and thymic NETs were contributed from Royal Brompton Hospital, London, UK, which included the cases during the period from 1982 to 1999. Each case was re-examined to confirm the diagnosis and cases with sufficient amount of tumor in the paraffin block for study were

TTF-1 expression

TTF-1 positivity was seen exclusively in pulmonary NETs. All thymic and abdominal/pelvic NETs were negative for TTF-1 (both TTF-I and TTF-E scores 0). Intensity and extent scores of each category and demographic details are summarized in Table 1. TTF-1 positivity was significantly higher in TL (72.7%) than in TC (27.8%), AC (29.4%), and LCNEC (37.5%; P = 0.03), but there was no significant difference among the TC, AC, and LCNEC cases (P = 0.66; Fig 1). Strong immunoreactivity, as in positive

Discussion

This study evaluates TTF-1 expression across a spectrum of pulmonary NETs, with the purposes of documenting prevalence in a series of neoplasms less well described than more common types of pulmonary neoplasm, comparing prevalence with extrapulmonary counterparts and assessing any differences across the spectrum of pulmonary NETs. To date, data on TTF-1 expression in TCs show considerable variation,11, 14, 16, 17, 18, 19, 20 and there are few data on TTF-1 expression in extrapulmonary ACs and

Acknowledgements

The authors thank Mr. Steven Claunch and Mrs. Wilma Flordeliza for their outstanding immunohistochemical staining and Dr. Unyoung Goh for her skilled statistical analysis.

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