Lung

• Pulmonary carcinoids are well differentiated neoplasms, with neuroendocrine differentiation further divided into typical and atypical carcinoids (neuroendocrine tumors grade 1 and 2)
• Classification is based on mitotic count per 2 mm² and the presence / absence of necrosis (Ki67 proliferative index is currently not recommended to distinguish between typical and atypical carcinoids)

Contributed by Philippe Joubert, M.D., Ph.D. and Case #266

Contributed by Simon Martel, M.D.

• Well circumscribed, round to oval tan colored tumors
• Localization
  • Frequently in bronchial lumen, sessile or pedunculated with partial or complete obstruction of the lumen
  • Peripheral tumors may not be evidently located in airways
• Size range: 0.5 - 9.5 cm
• Reference: Lung Cancer Int 2015;2015:545601

Contributed by Sylvain Trahan, M.D. and Yale Rosen, M.D.

Contributed by Philippe Joubert, M.D., Ph.D.

• Diagnostic criteria
  • Neuroendocrine tumor with size ≥ 5 mm with < 2 mitoses/2 mm² and absence of necrosis
• Neuroendocrine growth pattern (organoid, trabecular, rosette formation, nested) or pseudoglandular, follicular and papillary growth
• Tumor cells are uniform with a polygonal shape, round to oval nuclei with salt and pepper chromatin as well as inconspicuous nucleoli and moderate to abundant eosinophilic cytoplasm
  • Spindle cells and clear cell features can be seen
• Stroma is fine and highly vascularized; hyalinization, cartilage or bone formation are possible
• Reference: Curr Oncol 2018;25:S86

Contributed by Philippe Joubert, M.D., Ph.D., Jijgee Munkhdelger, M.D., Ph.D. and Andrey Bychkov, M.D., Ph.D.

Contributed by Philippe Joubert, M.D., Ph.D.

• Atypical carcinoid:
  • Well differentiated neuroendocrine tumor with > 2 mitoses/2 mm² or presence of necrosis
• Carcinoid tumorlet:
  • Well differentiated neuroendocrine tumor with size < 5 mm and with < 2 mitoses/2 mm² and absence of necrosis
• Small cell carcinoma:
  • Scant cytoplasm, elevated nuclear to cytoplasmic ratio, nuclear molding, absence of nucleoli
  • Ki67 proliferative index > 50%
• Large cell neuroendocrine carcinoma:
  • Large cells, high grade nuclei
  • High mitotic index, Ki67 proliferative index > 50%
• Paraganglioma:
  • Cytokeratins are negative
  • Also can have S100+ sustentacular cells
• Thyroid medullary carcinoma:
  • Calcitonin+, CEA+
• Well differentiated neuroendocrine tumor of the gastrointestinal tract:
  • CDX2+ (clinical correlation required if TTF1 and CDX2 are both negative)
• Type A thymoma:
  • p40+
  • Neuroendocrine markers (chromogranin, synaptophysin) are negative
• Prostatic adenocarcinoma (if cribriform or neuroendocrine features):
  • PSA+, ERG+, NKX3.1+
• Breast carcinoma:
  • CK7+, GATA3+, frequently ER+

A 55 year old woman had a lower left lobectomy showing a well circumscribed flesh colored tumor. Histologic details are shown in the image above. Regarding this entity, which of the following statements is true?

1. CDX2 is usually negative in the lung and is useful to differentiate from a metastasis of an intestinal origin
2. Ki67 proliferative index is essential to grade this tumor
3. Rb expression is typically lost in this tumor
4. TTF1 is always positive

A. CDX2 is usually negative in the lung and is useful to differentiate from a metastasis of an intestinal origin. The image shows a tumor with a trabecular pattern and pseudorosettes. The stroma is highly vascularized. Tumor cells are monotonous with scant to moderate eosinophilic cytoplasm. Nuclei are round to oval with salt and pepper chromatin and inconspicuous nucleoli. No mitoses are seen. These features are consistent with a typical carcinoid lung tumor.

Ki67 immunostaining, counter to well differentiated neuroendocrine tumors from the gastrointestinal tract, is not essential to grade the tumor. The difference between typical and atypical tumor relies on mitosis count and the presence of necrosis. However, Ki67 is useful to differentiate from high grade neuroendocrine tumors (small cell and large cell neuroendocrine carcinomas) on small biopsies with artifacts. TTF1 is positive in only half of cases with a higher frequency in peripheral tumors. Rb expression is preserved in typical carcinoid lung tumors, unlike in small cell tumors.

Comment Here

Reference: Carcinoid tumor / neuroendocrine tumor, grade 1

Regarding typical carcinoid tumors of the lung, which of the following statements is true?

1. Diagnostic criteria are based on mitotic rate and Ki67 proliferation index
2. Most patients are smokers
3. They are mostly found in peripheral airways
4. They may arise in the context of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia and tumorlets

D. They may arise in the context of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia and tumorlets. Development of carcinoid tumors of the lung is not well understood but some cases are associated with diffuse idiopathic pulmonary neuroendocrine cell hyperplasia and tumorlets. The other statements are false. Even though lung carcinoids are found in association to airways and can be found all over the bronchial tree, most of them are centrally located (C). Typical carcinoids are not related to smoking (B). The diagnostic criteria of carcinoid tumors of the lung differ from the ones of well differentiated neuroendocrine tumors of the gastrointestinal tract (A). In the lung, the classification is based on mitotic count per 2 mm² and presence / absence of necrosis. Typical carcinoids have a mitotic rate of 2 mitoses/2 mm² and no necrosis, while atypical carcinoids have a mitotic rate of 2 - 10 mitoses/2 mm² or a presence of necrosis.

Comment Here

Reference: Carcinoid tumor / neuroendocrine tumor, grade 1