Atypical Carcinoid Tumor of the Larynx: An Immunohistochemical, Ultrastructural, and Flow Cytometric Analysis

Abstract

The clinicopathologic features, including a detailed immunohistochemical, ultrastructural, and flow cytometric analysis, are described in three cases of atypical carcinoid tumor of the larynx. All patients had metastatic disease within cervical lymph nodes at presentation and eventually developed distant metastases. Special stains revealed focal intracytoplasmic mucin accumulation, and immunohistochemistry showed the tumors to be positive for CAM 5.2, CEA, chromogranin A, and calcitonin. In two cases, double-staining techniques revealed occasional cells that stained for both mucin and chromogranin A. The histochemical and immunohistochemical findings in these two cases were confirmed at the ultrastructural level, with most tumor cells containing many neurosecretory granules. Smaller numbers of cells contained mucin vacuoles and, in occasional cells, both mucin and neuroendocrine granules were identified. The three tumors exhibited positive staining with D07 (anti-p53), and flow cytometric analysis revealed DNA aneuploidy and polyploidy. The double-staining and ultrastructural features indicate that laryngeal atypical carcinoid qualifies for the designation of true amphicrine carcinoma. Further study is necessary to determine whether mutation of the p53 gene is important in the evolution of laryngeal neuroendocrine tumors and whether DNA aneuploidy or polyploidy identifies a subset of these tumors with a poor prognosis.

Thyroid transcription factor-1, but not p53, is helpful in distinguishing moderately differentiated neuroendocrine carcinoma of the larynx from medullary carcinoma of the thyroid

“…22,23 In contrast, it has been suggested that p53, which has been shown to be diffusely positive in three laryngeal moderately differentiated neuroendocrine carcinomas, may play a role in the pathogenesis of this tumor, unlike other neuroendocrine tumors. 5 However, these findings have not been validated.…”

“…Currently, serum calcitonin is the only objective means for distinguishing primary moderately differentiated neuroendocrine carcinoma of the larynx from metastatic medullary carcinoma, as calcitonin immunohistochemistry is reportedly positive in both tumors. [3][4][5][6] Thyroid transcription factor-1 (TTF-1) is a nuclear homeodomain transcription factor that is selectively expressed in developing respiratory epithelium, thyroid and diencephelon. 7,8 Immunohistochemical studies have shown that TTF-1 is expressed in a subset of lung and most thyroid neoplasms, including pulmonary neuroendocrine tumors and medullary carcinoma of the thyroid.…”

“…p53 was also studied as a potential discriminator as at least one prior investigation has suggested that it may be a useful marker for moderately differentiated neuroendocrine carcinomas. 5 …”

Clinical recommendations on the treatment of neuroendocrine carcinoma of the larynx: A meta-analysis of 436 reported cases

“…The literature on NCL is fragmented over numerous case reports and series of small sample size, often with contradicting results, making it difficult to decide on an appropriate treatment strategy. Consequently, physicians facing these tumors often resort to treatment paradigms developed for better known neoplasms (eg, squamous cell carcinoma).…”

Cutaneous and Subcutaneous Metastases From Atypical Laryngeal Carcinoids

“…Chung et al (2004) 34 found that 3 of 6 patients with moderately differentiated laryngeal NECs were p53-positive. McCluggage et al (1997) 35 also reported that 3 atypical laryngeal carcinoid patients were p53-positive. Overholt et al (1995) 36 found that 6 of 8 patients with laryngeal neuroendocrine neoplasms (including 2 atypical carcinoids) were p53-positive.…”