Lung - Large Cell Neuroendocrine Carcinoma
Transcript of Lung - Large Cell Neuroendocrine Carcinoma
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FLASHPATHH a z e m A l i
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LARGE CELL NEUROENDOC
RINE CARCINOMA
H a z e m A l i
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CLINICAL
Carcinoid tumors are part of the spectrum of neuroendocrine lung tumors that includes:• Large cell neuroendocrine carcinoma• Small cell carcinoma• Typical carcinoid• Atypical carcinoid
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CLINICAL
• High grade neuroendocrine carcinoma
• < 3% of primary lung tumors
• More common in adults
• Strong association with smoking
• Ectopic hormone secretion is NOT a feature.
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CLINICAL
• More likely to develop recurrent lung cancer (poor prognosis)– The overall survival at five and 10 years is poor, approximately 20% and 10%,
respectively.– Usually have shorter survival than patients with other histologic types of NSCLC,
even in those with stage I disease
• Surgery has no/limited role and the usual treatment is chemotherapy (similar to small cell carcinoma)
– Remember that carcinoid tumors usually treated surgically.
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GROSS
• Can extensively replace lung
• Can be central or peripheral
• Can be multinodular
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MICROSCOPIC• Patterns: at least focal
– Organoid– Trabecular– Palisading– Rosettes formation
• Tumors cells:– Large, polygonal cells with abundant cytoplasm (low N/C ratio)– Nuclear pleomorphism– Vesicular, coarse, or fine chromatin– Visible, prominent nucleoli
• High mitotic rate (>10 mitoses/10 hpf)• Necrosis is prominent“Resembles non-small cell carcinoma cytologically, but on closer inspection has a hint of neuroendocrine architecture confirmed by special stains” - Rosai
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SPECIAL STUDIES• Neuroendocrine markers
– Chromogranin, Synaptophysin, Neuron Specific Enolase, and CD56– May show reduced staining
• Pan-keratin– Cam 5.2 is better than AE1/AE3 (to be safe, use both)
• TTF-1 • Ki67 (Mib1)
– More than 20%
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SPECIAL STUDIES• Chromogranin:
– Acidic glycoprotein in neurosecretory granules– (Cytoplasm, granular)
• Synaptophysin:– Transmembrane glycoprotein found in presynaptic vesicles– (Cytoplasm, granular)
• CD56:– NCAM “Neural Cell Adhesion Molecule”– (Membranous)
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SPECIAL STUDIES• Overall, SYN and CD56 are more sensitive than CHR but CHR is more specific.
• CD57 can be used as “2nd line” neuroendocrine marker
• NSE is no longer used in neuroendocrine tumors diagnosis (very low specificity)
• Some NE tumors will label for either CHR or SYN but not both– so to be safe, use both
• SYN and CHR are usually strongly expressed in low-grade NE neoplasms (e.g. carcinoid), whereas expression may be weak/focal in high-grade NE neoplasms (e.g. small cell carcinoma)
– Fortunately, CD56 is positive in high-grade NE tumors
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SPECIAL STUDIES
Electron microscopy: Dense-core secretory granules– Membrane-limited dense-core granules– Vary in size (50–400 nm), shape, and density
• depending on the protein contained in the granule– Usually have a halo between the core and the membrane
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CYTOLOGY• Cellular smear• Large polygonal to oval cells• Cells tend to focally organize as rosettes or cords with palisaded nuclei• Nuclei are variable in size and shape, but usually large.
– Should be more than three times the size of a resting lymphocyte• Chromatin may be:
– Vesicular with prominent nucleoli (mimicking adenocarcinoma)– Coarse and stippled with occasional nucleoli (mimicking small cell carcinoma)
• Obvious mitotic activity and necrotic debris
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DIFFERENTIAL DIAGNOSIS
• Other neuroendocrine tumors:– Carcinoid tumor– Small cell carcinoma
• Other tumors:– Adenocarcinoma– Large cell undifferentiated carcinoma– Mesothelioma– Lymphoma– Melanoma
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DIFFERENTIAL DIAGNOSISCarcinoid Tumor• Organoid pattern is well-formed• Higher N/C ratio than LCNEC• Bland nuclei
– Except atypical cases that may show mild pleomorphism• Inconspicuous nucleoli• Low mitosis
– Typical: < 2 mitoses/10 hpf– Atypical: 2 – 10 mitoses/10 hpf
• Low Ki67 (Mib1)– Typical: < 2%– Atypical: 2 – 20%
• No necrosis– May be seen (but less extensive) in atypical cases
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DIFFERENTIAL DIAGNOSIS
Small cell lung carcinoma (SCLC):• Absent organoid pattern• Small cells with scant cytoplasm (High N/C ratio)• Nuclear molding• Nuclear pleomorphism• Fine granular chromatin• Absent nucleoli
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DIFFERENTIAL DIAGNOSIS
Other Tumors:• No evidence of neuroendocrine differentiation by light microscopy or IHC
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