Case 7
Clinical features :
Female patient, 18 years old, member of an isolated-CMT family, carrying the
germline mutation of protooncogene Ret
Basal serum Calcitonine level : 35 ng/L - with Pentagastrine stimulation : 125 ng/L.
Gross features :
Total thyroidectomy 18 grs resected en bloc with central lymphadenectomy. In the
absence of palpable tumor, the specimen is fixed in formalin fluid without frozen section.
Each lobe is sectioned transversaly in 2-3 mm slices from the upper to the inferior pole,
and systematic Calcitonin (CT) immunostaining is realized on each block.
| Microscopy : |
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| The sections corresponding to the upper 1/3 include several
micro foci of MCT (medullary thyroid carcinoma), sometimes near a Solid Cell Nest (fig A). |
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fig. A |
| The tumor shows a lobular or a trabecular pattern (fig B) of round or polygonal
rather eosinophilic cells (fig B). |
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fig. B |
| C Cell Hyperplasia (CCH) is detectable in routine staining (fig C) around follicles whereas
normal C cells are not visible by this staining. Each tumor focus mesure less than 2mm. |
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fig. C |
| Immunostaining with Calcitonin antibody is positive on micro
MTC (fig D) and CCH (fig E) ; there is also a strng
positivity well with CEA antibody. |
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fig. D |
| No lymph nodes metastasis have been found. |
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fig. E |
Diagnosis :
Bilateral micro- medullary carcinoma of the thyroid with CCH, suggestive of familial
form ; intra thyroid, without lymph node involvment p T1 N0
Comments :
Familial MTC - with or without MEN II A or B - are histologically characterized by
2 signs : bilaterality and CCH. In young people, particularly in children, the tumors are
very small or there is only CCH. For that reason, it is necessary to study carefully the 2
lobes by macroscopic serial step sections, with CT - immunohistochemical study.
The diagnostic problems are :
- no detection of very small tumors if unadequate technique
- distinction between pathologic-CCH and physiologic-CCH : in the
literature, there is variation in the level but the usual criterion is " more than 50
C cells at low magnification (X10) on 3 fields " Physiologic CCH is diffuse,and not
visible in routine section, opposite to pathologic CCH, often nodular
- the distinction between florid nodular CCH filling all the follicle
and micro-MTC is often very difficult : the diagnosis is based on the presence of fibrous
stroma or small amyloid deposit. The study of follicular basal membrane disruption can be
helped by PAS or antibody anti-collagen IV.
Recognizing patients with germline mutation of Ret oncogene allows early diagnosis even if
serum CT is not elevated : this is very important to avoid lymph node invasion like in
this case.
References :
PERRY A MOLBERG K ALBORES-SAAVEDRA J :
Physiologic versus neoplastic C cell hyperplasia of the thyroid .Separation of distinct
histologic and biologic entities.
Cancer 77 : 750-756 ,1996
KASERER K , SCHEUBA C, NEUHOLD N, and all
Sporadic versus familial medullary thyroid carcinoma
Am J Surg pathol. 25 (10) : 1245-1251, 2001
Mc DERMOTT MB SWANSON PE WICK MR
Immunostain for collagen IV discriminate between C cell hyperplasia and microscopic
medullary carcinoma in multiple endocrine neoplasia, type 2
Hum. Pathol. ; 26 : 1308- 12 , 1995
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