Lung Neuroendocrine Tumors Flashcards
According to Dr. Moran, what 3 types of diagnosis are possible for tumors showing neuroendocrine expression and large cells?
- Large Cell Neuroendocrine carcinoma
- Adenocarcinoma or Squamous cell carcinoma with Neuroendocrine like architecture –> Called Carcinoma with Neuroendocrine features
- Adenocarcinoma or Squamous cell carcinoma with Neuroendocrine staining pattern –> Called carcinoma with Neuroendocrine differentiation
Note: up to 25% of adenocarcinomas and squamous cell carcinomas can have neuroendocrine like features or differentiation but they are not actually large cell neuroendocrine carcinomas.
What is the proposed cell origin of Neuroendocrine tumors of the lung?
Kulchitsky cells
What are some macroscopic features of Neuroendocrine carcinomas?
- endobronchial or intraparenchymal tumor
- High-grade tumor may show extensive areas of necrosis
- Size: 0.5 to >10 cm
What are the diagnostic features of Low-grade tumors (Carcinoid Tumor)?
- No necrosis is allowed
- Up to 3 mitosis per 10 HPF allowed
- May have mild nuclear atypia
- Well-organized microscopic pattern:
- Nested (may be separated by delicate bands of fibroconnective tissue)
- Diffuse
- Glandular/Pseudoglandular - can mimic adenocarcinoma
- Rosette formation
- Spindle cell pattern can be prominent but should be bland
- Spindle Cell Carcinoid
- Hemangiopericytoma-like (surrounding ectatic vessels)
What are the diagnostic features of Intermediate-grade tumors (Atypical CarcinoidTumor)
- Tumors with 4-10 mitosis per 10 HPF
- Necrosis may be seen (comedo-like)
- Similar architectural patterns may be identified
- But you will typically have a combination of well-organized nested pattern and diffuse pattern of growth.
IMP: in the glandular architecture, usually you have small cells lining the glands, but no mitotic activity is noted.
What are the diagnostic features of High-Grade Neuroendocrine Carcinoma?
- >10 mitotic figures per 10 HPF
- Necrosis is present
- The types of tumors in this category are:
- Large cell neuroendocrine
- Small cell carcinoma
What are necessary features of Large Cell Neuroendocrine Carcinoma?
- Neuroendocrine growth pattern AND positive staining with neuroendocrine markers
- Chromogranin-A, Synaptophysin and CD56
- Cells with prominent nucleoli
- Comedo-like necrosis
What are the features of small cell carcinoma?
- Mitotic figures >10 per 10 HPF (only applies to resected specimens)
- Minimal cytoplasm, nuclear molding
- Presence of apoptotic bodies and necrosis
IMP: Neuroendocrine markers are NOT required for diagnosis.
What predominant patterns and cell types can be seen in Neuroendocrine tumors of the lung?
Predominant Pattern:
- Nesting, diffuse, glandular
- Mucinous
Predominant Cell Type:
- Oncocytic
- Spindle
- Melanocytic
- Epithelial, neuroendocrine
- Clear (extensive areas of clear cell change is rare)
What is the differential diagnosis of neuroendocrine tumors of the lung?
- Various grades of NE tumors (low-high)
- Carcinoid tumorlet (DIPNICH)
- usually <5 mm in diameter
- Metastatic neuroendocrine carcinoma (extrathoracic)- do TTF-1 may be helpful
- Pulmonary paraganglioma
- Large cell carcinoma:
- Large cell neuroendocrine carcinoma
- with NE differentiation
- with NE pattern
What are the clinical issues regarding a pulmonary paraganglioma?
- Extremely rare tumor in pulmonary primary location
- Middle aged adults (40-50 years)
- Male predominance
Presentation:
- solitary, peripheral coin lesion
- central, peribronchial lesion
- Endocrine symptoms: HTN, increased serum Norepi, Cushing syndrome
- Endobronchial lesions present with obstructive symptoms
What are the macroscopic features of pulmonary paragangliomas?
- well-circumscribed, intraparenchymal lesion
- smooth, well-circumscribed endobronchial lesion
- 1-3 cm in greatest dimension
- cut surface:
- smooth, homogenous and well-circumscribed
- tan-brown to pink
- highly vascularized, may show hemorrhage rarely
What are the histologic features of pulmonary paraganglioma?
- endocrine or organoid growth pattern
- Zellballen pattern: most common, discrete nests of tumor cells separated by fibrovascular septa
- Rarely cases may show prominent stromal sclerosis
- Necrosis or vascular invasion rarely encountered
- Stroma may be very vascularized with large, ectatic vessels
- Rare patterns: trabecular, microacinar, ribbon-like
What are the cytologic features of pulmonary paraganglioma?
- Large, round or polygonal cells with abundant eosinophilic cytoplasm
- Large, round cells with abundant clear cytoplasm
- elongated cells with spindled nuclei and abundant cytoplasm
- Oncocytic cells with abundant granular, eosinophilic cytoplasm
- Cell nuclei are generally small –> contain inconspicuous nucleoli
- Foci containing large, bizarre nuclei are frequent but devoid of mitotic activity
- If mitosis are present they should not be atypical
- Intranuclear cytoplasmic inclusions (pseudoinclusions) can be occasionally identified
What is the immunohistochemistry of pulmonary paraganglioma?
- Strong positive: Chromogranin, synaptophysin, CD56
- S100 protein positive in sustentacular cells
- Should be negative for cytokeratins !
