By Ivan Damjanov MD, PhD (auth.), Ivan Damjanov MD, PhD, Fang Fan MD, PhD (eds.)
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The characteristic “lepidic” growth pattern of bronchioloalveolar cell carcinoma is evident, with a row of mildly atypical cells continuously lining the alveolar walls. C. Tall, columnar cells with abundant clear mucinous cytoplasm form this bronchioloalveolar cell carcinoma. D. This moderately differentiated adenocarcinoma is composed of ill-deﬁned glands, with small, abortive lumina, lined by atypical cells. It also contains solid areas with nuclear stratiﬁcation. E. A poorly differentiated adenocarcinoma exhibits ill-deﬁned glands lined by highly atypical cells.
Zidar Comments 1. The majority of laryngeal squamous cell carcinomas are well to moderately differentiated, whereas the majority of hypopharyngeal squamous cell carcinoma are moderately to poorly differentiated. 2. Variations in differentiation are frequently observed within a single tumor, but grading must be based on the worst differentiated area. 3. The prognostic signiﬁcance of traditional grading of squamous cell carcinoma is controversial. Some studies have suggested that the grade has a signiﬁcant inﬂuence on prognosis (3,4), while others have not conﬁrmed this observation (5).
The diagnosis of LCNEC requires conﬁrmation by immunohistochemistry (positivity for neuroendocrine markers such as chromogranin-A or synaptophysin), or demonstration of dense-core neurosecretory granules by electron microscopy. Comments 1. A variable spectrum can sometimes be observed between well-differentiated NEC and moderately differentiated NEC, occasionally making exact distinction between them difﬁcult. The most important criterion for separating them is mitotic activity. 2. Although it was initially thought that atypical carcinoid required more than 5 mitoses per 10 hpf, that threshold has been lowered recently, and tumors displaying 2 or more mitoses per 10 hpf are classiﬁed as moderately differentiated NEC.