Well-Differentiated Neuroendocrine Carcinoma, Thymic Carcinoid, [Pathology] Atlas of Well-Differentiated Neuroendocrine Carcinoma (“Thymic Carcinoid”), Neuroendocrine Neoplasms of the Thymus
Neoplastic neuroendocrine proliferations of the mediastinum can originate from neuroendocrine cells that are native to the thymus, or they may arise from extra-adrenal paraganglia ectopically located in the mediastinum (i.e., paragangliomas).
Neuroendocrine carcinomas originating in the thymus are most common in middle-aged adults, with a male predilection, and can encompass the entire spectrum from welldifferentiated tumors that are similar to their counterpart in other organs (i.e., carcinoid tumors) to poorly differentiated, highly malignant neoplasms (such as small cell neuroendocrine carcinomas). The term “carcinoid tumor,” which has been used in the past, is best replaced by “well-differentiated neuroendocrine carcinoma” or “low-grade neuroendocrine carcinoma,” given that the malignant potential of these lesions has now been amply established. In up to one-third of patients, these tumors can be associated with paraneoplastic syndromes, including Cushing’s syndrome, syndrome of inappropriate secretion of antidiuretic hormone, and the Eaton-Lambert syndrome. Up to one-third of cases also occur in association with the multiple endocrine neoplasia (MEN) types I and II syndromes.
The classification of neuroendocrine carcinomas in the mediastinum has remained controversial. Although the current World Health Organization (WHO) classification retains the terms “carcinoid” and “atypical carcinoid” for some of these tumors, the current trend is to use the term “well- differentiated neuroendocrine carcinoma” for “carcinoid” and to use “moderately differentiated neuroendocrinecarcinoma” for “atypical carcinoid.” The new terms more accurately and realistically denote the actual biologic behavior of these tumors, whereas the WHO schema lumps typical carcinoid and atypical carcinoid under the category of welldifferentiated neuroendocrine carcinoma, implying that they share a similar biologic behavior. The most recent large study (Moran and Suster, Am J Clin Pathol; 2000), however, has demonstrated that there is a stepwise progression in malignant behavior that is directly related to prognosis for these tumors as they progress from well-differentiated to moderately differentiated to poorly differentiated types.
Thus, separation of well-differentiated tumors from moderately or poorly differentiated tumors is warranted.
Table 3.1 presents the criteria for histologic diagnosis of primary neuroendocrine carcinomas of the thymus. In general, increasing grade of malignancy in these tumors translates into increased cytologic atypia and loss of architectural, organotypical features of neuroendocrine differentiation.
The morphologic spectrum displayed by these tumors can be quite variable, and numerous unusual morphologic variants have been described. Correct diagnosis in such instances requires awareness of these variants, which must be considered in the differential diagnosis so that an appropriate immunohistochemical workup can be initiated.
Well-Differentiated Neuroendocrine Carcinoma (“Thymic Carcinoid”)
The growth patterns and cytologic characteristics of neuroendocrine carcinomas of the thymus (Figs. 3.1, 3.2, 3.3, 3.4, 3.5, and 3.6, Table 3.2) can be quite varied.
Fig. 3.1 Gross appearance of well-differentiated neuroendocrine
carcinoma of the thymus (thymic carcinoid) shows a well-circumscribed,
fleshy, tan-white mass with foci of hemorrhage and a vaguely lobulated
cut surface
Fig. 3.2 Scanning magnification of well-differentiated neuroendocrine
carcinoma of the thymus (thymic carcinoid) shows well- developed
“organoid” (neuroendocrine) architecture, with discrete nests of tumor
cells separated by fibrovascular stroma
Fig. 3.3 Higher magnification of well-differentiated neuroendocrine
carcinoma of the thymus with “organoid” (neuroendocrine) growth
pattern shows well-defi ned small nests of cells containing a monotonous,
round cell population with abundant cytoplasm and small, round to oval
nuclei with stippled (“salt-and-pepper”) chromatin pattern
Fig. 3.4 High power of well-differentiated neuroendocrine carcinoma
of the thymus shows round cells with round to oval nuclei showing a
stippled chromatin pattern with an ample rim of eosinophilic
cytoplasm
Fig. 3.5 Another example of the organoid, nested (“tzellballen”)
growth pattern in thymic neuroendocrine carcinoma shows larger nests
of monotonous tumor cells separated by thin and compressed fibrovascular septa
Fig. 3.6 Higher magnification of Fig. 3.5, showing well-differentiated
neuroendocrine carcinoma of the thymus with a monotonous population of
small, round cells surrounded by abundant eosinophilic cytoplasm. A few
isolated tumor cells show a small nucleolus, but there is
no evidence of necrosis, nuclear pleomorphism, or mitotic activity
Table 3.2 Growth patterns and cytologic variants of thymic neuroendocrine carcinomas
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