Case 008 - 61 Year Old Male with a Lung Mass and Spraclavicular Adenopathy

Contributed by Andre Thompson, M.D., Supervised by Lillian Gaber, M.D.

Clinical History

The patient is a 61-year-old African-American male who presented to the ER with fever, productive cough and right chest pain X 3 months. History is significant for smoking 1/2 pack per day X 15 years. Physical exam revealed rales and decreased breath sounds in the right lung, and enlarged left supracalvicular lymph node. Chest CT showed bilateral pleural effusion and a 7 X 4 cm right hilar mass involving the right main stem bronchus and extending into the superior mediastinum, with hilar, mediastinal and left supraclavicular adenopathy. The enlarged left supracalvicular lymph node was excised and sent to pathology.

Gross Findings

The specimen is a 2.8 X 2.5 X 1.5 cm red-brown soft tissue fragment. Sectioning the fragment reveals a pink-white, focally hemorrhagic cut surface.

Microscopic Findings

(Click a photo to view a larger image.)

Image (1) H&E, 2xImage (2) H&E, 4xImage (3) H&E, 10xImage (4) H&E, 20xImage (5) H&E, 20xImage (6) H&E, 40xImage (7) H&E, 60xImage (8) Pankeratin, 4xImage (9) S 100, 40xImage (10) Synaptophysin, 4xImage (11) Vimentin, 4x


Metastatic Large Cell NeuroEndocrine Carcinoma (LCNEC)

The lymph node architecture is effaced by a poorly-differentiated tumor. On low power, the tumor shows a lobular architecture, prominent necrosis, and perinodal soft tissue involvement with intravascular invasion. On high power, tumor cells are large in size with high N:C ratio; eosinophilic cytoplasm, pleomorphic nuclei with coarse chromatin, prominent nucleoli, and high mitotic rate.

Immunoperoxidase stains demonstrate diffuse strong positive reaction for synaptophysin and vimentin. Tumor cells are negative for S 100, pankeratin, EMA, HMB 45, PLAP, CD 45, CD 30, and Leder.


The CT findings of multifocal lymphadenopathy with a right hilar/mediastinal mass called for a broad differential including pulmonary, hematologic, melanocytic, and other malignancies. Our incline was to first look for a lung primary. The negative reaction to pankeratin and S-100 initially steered us away from the lung, and a battery of immohistochemical studies ensued. Eventually, the combination of clinical data, tumor morphology, and reactivity to synaptophysin favored the diagnosis of Large cell neuroendocrine carcinoma (LCNEC).

LCENC was added to the WHO classification in 1999 as a variant of large cell carcinoma. Along with small cell lung carcinoma (SCLC), LCNEC belongs to the high grade end of the spectrum of neuroendocrine tumors of the lung, as compared to typical carcinoid (low grade) and atypical carcinoid (intermediate grade).

The diagnosis of LCNEC is based on recognition of both neuroendocrine morphology (organoid pattern; palisading; rosette-like formation; >10 mitoses per 10 HPF; and vesicular nuclear chromatin) and the immunohistochemical demonstration of at least one specific neuroendocrine marker (synaptophysin, chromogranin, neural cell adhesion molecule). Synaptophysin antibody has been shown to be the most sensitive and most specific screening immunostain for neuroendocrine tumors. Chromogranin A antibody is the most specific marker of normal and neoplastic neuroendocrine cells.

Immunohistochemical evidence of neuroendocrine differentiation has been found in in 5-10% of non-small cell lung carcinoma (NSCLC) that do not display any neuroendocrine (organoid) morphology. This does not allow a specific classification and is collectively referred to as no-small cell lung carcinoma with neuroendocrine differentiation (NSCLC-ND); the prognosis of these tumor is controversial.

Studies have shown a significant difference in survival rate between LCNEC and atypical carcinoid but NO difference in survival rate between LCNEC and SCLC.


  • E. Brambilla et al. The new World Health Organization classification of lung tumors. Eur Respir J 2001; 18: 857-866
  • M.C. Howe et al. Neuroendocrine differentiation in non-small cell lung cancer and its relation to prognosis and therapy. Histopathology 2005; 46: 195-201
  • G. Rossi et al. TTF1, Cytokeratin 7, 34ßE12m and CD56/NCAM immunostaining in the subclassification of Large Cell Carcinoma of the lung. Am J Clin Pathol 2004; 122: 884-893
  • D. Dabbs. Diagnostic immunohistochemistry, 1st edition; pp 270-271
  • Rosi and Ackerman’s Surgical Pathology; 9th edition Vol-1; pp 411-412

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