23
Thyroid
Fig. 23.12 Medullary carcinoma. (A) Cellular smear showing isolated cells and small loosely cohesive group of cells. The cytoplasms are clear with ill-defined
limit and fine bluish granularity. The nuclei are round to oval (May-Grunwald-Giemsa x HP). (B) Loosely cohesive group of cells with eccentric cytoplasms and
anisokariosis (May-Grunwald-Giemsa x HP). (C) Disperse spindle cells with elongated nuclei, speckled chromatin, and small nucleoli (May-Grunwald-Giemsa
x HP). (D) Detail shows mono- and binucleated cells with ill-defined cytoplasmic limits and polarized nuclei and fine intracytoplasmic metachromatic granules
(May-Grunwald-Giemsa x OI).
typical nuclear features (macronucleoli) of neoplastic Hurthle
cells. Although the cytoplasmic granules have diagnostic value,
they are not pathognomonic, having been described in follicu-
lar tumors, anaplastic carcinoma, and metastatic carcinoma of
the breast (see Fig. 23.12D); moreover, they are not seen in all
cases or in all cells.211,213
Very large isolated nuclei, binucleate (plasmacytoid), or multi-
nucleated cells are sometimes seen (Fig. 23.13A).215 Occasion-
ally, nuclear cytoplasmic inclusions similar to those of papillary
carcinoma are observed (Fig. 23.13B).210,212 In some cases, a dense
amorphic material that stains similarly to colloid, but demon-
strates the characteristic birefringence of amyloid when stained
with Congo red and examined under polarized light, is found
(Figs 23.13C and 13D). Exceptionally, reports have been made
of melanin pigment in the cytoplasm of tumoral cells,216 calcified
bodies resembling psammoma bodies,217 and intracytoplasmic
vacuoles and lumina with mucus production.218,219
The differential diagnosis should be made mainly with Hurthle
cell tumor, hyalinizing trabecular tumor, papillary carcinoma,
anaplastic carcinoma, and metastatic neoplasms, particularly
malignant
melanoma.
Malignant
melanoma
may
mimic
medullary carcinoma because it may contain plasmacytoid and
pleomorphic cells. The most characteristic findings to support
the diagnosis of medullary carcinoma are abundant isolated cells
with marked variations in size and form, plasmacytic-like cells,
and presence of metachromatic cytoplasmic granules. Whenever
possible, the diagnosis should be supported by immunostain-
ing for calcitonin, CEA, synaptophysin, or chromogranin, or by
ultrastructural studies because both methods provide definitive
information.220 In doubtful cases showing a mixed pattern, the
possibility of an admixed neoplasm, whether follicular carci-
noma and medullary carcinomas or papillary carcinoma and
medullary carcinoma cells, should be considered.221,222
Poorly Differentiated Thyroid Carcinoma
Also known as insular carcinoma, it represents an intermediate
tumor between differentiated follicular cell carcinoma (follicular
carcinoma and papillary carcinoma) and anaplastic carcinoma.
The disease is slightly more frequent in women, and the mean age
of presentation is 55 years. Grossly, the tumors are usually larger
than 5 cm and often show invasive margins and necrotic foci.
The tumoral cells have a variable degree of pleomorphism and
655
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