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Sabato 27 ottobre 2012 - Pacini Editore

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COmuNiCaziONi ORali<br />

and hindgut origin: tumor-node-metastasis classification determines<br />

clinical outcome. Cancer 2011;117:3332-41.<br />

9 Couvelard A, Deschamps L, Ravaud P, et al. Heterogeneity of tumor<br />

prognostic markers: a reproducibility study applied to liver metastases<br />

of pancreatic endocrine tumors. Mod Pathol 2009;22:<strong>27</strong>3-81.<br />

Immunocytochemistry and BrAF mutation analysis<br />

in thyroid lesions suspicious for malignancy<br />

diagnosed on liquid- based cytology.<br />

A new challenge<br />

E.D. Rossi, M. Martini, P. Straccia, S. Capodimonti, T. Cenci,<br />

C.P. Lombardi1 , A. Pontecorvi2 , L.M. Larocca, G. Fadda<br />

Division of Anatomic Pathology and Histology 1 Division of Endocrine<br />

Surgery, 2 Division of Endocrinology- Università Cattolica del Sacro Cuore,<br />

“Agostino Gemelli” School of Medicine, Rome<br />

Introduction. Follicular patterned lesions are a common finding<br />

in general population for which a preoperative cytological diagnosis<br />

in order to define a correct therapeutical management, is<br />

crucial. Approximately 65-70% of fine needle cytologic biopsies<br />

(FNC) are classified as benign as well as 5-10% are diagnosed<br />

as malignant. The remaining 25-30% are included in the grey<br />

zone of the indeterminate diagnoses where benign neoplasms<br />

cannot be cytologically distinguished by the malignant ones. The<br />

Suspicious for Malignancy (SM) category represents a cytologic<br />

category in which the morphology alone is not able to define<br />

conclusively the malignant nature of a defined lesion. The aim of<br />

this study is the evaluation of the role of simultaneous analyses of<br />

immunocytochemistry and BRAF mutation in predicting the outcome<br />

of SM thyroid follicular lesions diagnosed on liquid based<br />

cytology (LBC), and, hence, in adding further diagnostic details<br />

which could guide a better clinical management. Immunocytochemistry<br />

based on the use of an immunopanel (e.g. HBME-1<br />

and Galectin 3) has shown a significant role in a better definition<br />

of low and high risk follicular neoplasms. Activating mutations<br />

in the V600E locus of BRAF-1 gene have been identified in about<br />

29-69% of PTC and more than 80% of the tall cell variant (TCV)<br />

whereas they have not been detected in benign lesions and in the<br />

majority (80%) of the follicular variants of PTC (FVPC).<br />

Materials and methods. From October 2010 through June 2011,<br />

43 SM, processed by liquid based cytology (LBC), were studied<br />

for the application of an immunopanel made up of HBME-1 and<br />

Galectin- 3 and for the BRAF mutational analysis. The aspirated<br />

material was processed with the ThinPrep 2000 technique (Hologic<br />

Co, Marlborough MA). Immunocytochemistry, carried out<br />

with the ABC peroxidase method and BRAF mutation analysis,<br />

using the direct sequencing method, were performed on the residual<br />

cells stored in the PreservCyt solution.<br />

Results. Thirty one cases out of 43 (73%) underwent surgery and<br />

were diagnosed respectively as: 5 benign lesions (BL, including<br />

Follicular Adenoma), 17 papillary carcinomas, (PTC), 7 follicular<br />

variants of papillary carcinoma (FVPC) and 2 tall cell variants<br />

of PC (TCV). All BL resulted negative for the immunopanel<br />

while all the malignant lesions resulted positive. All 12 cases that<br />

expressed the BRAF mutation (39%) resulted histologically malignant<br />

whereas all BL expressed BRAF wild type. A significant<br />

association between BRAF mutation and cancer multifocality<br />

was found (p < 0.0001, Odd Ratio, OR 0.003). The presence<br />

of BRAF mutation was also significantly associated with nodal<br />

involvement (p < 0.0001, OR 0.0061) and extracapsular invasion<br />

(p = 0.0001, OR 0.011). A significant association between the<br />

positive ICC panel and the malignant nature of the tumors was<br />

assessed (p = 0.0007 OR 55).<br />

Conclusions. Immunocytochemistry and BRAF gene mutation<br />

analysis can be successfully carried out on LBC-processed material.<br />

The simultaneous application of the two techniques on preoperative<br />

cytology may help in identifying up of 39% carcinomas<br />

among the category of SM supporting a more aggressive surgical<br />

329<br />

decision. In this group a significant correlation with nodal involvement<br />

and multifocality highlights the role of BRAF analysis<br />

in discriminating tumours with a more aggressive behaviour from<br />

those pursuing a favourable clinical course.<br />

references<br />

1 Rossi ED, et al. Cancer Cytopathol 2005;105:87-95.<br />

2 Nikiforova MN, et al. Thyroid 2009;19:1351-61.<br />

3 Nikiforov YE, et al. J.Clin Endocrinol Metab 2009;94:2092.<br />

4 Fadda G, et al. Eur J Endocrinol 2011;165:447-53.<br />

A case of hyalinizing trabecular tumor (HTT) of the<br />

thyroid gland in patient with multinodular goiter<br />

G. Crisman1 , A. Marinucci1 , A.R. Vitale2 , T. Curti2 , V. Ciuffetelli3<br />

, S. Saltarelli3 , G. Calvisi3 , G. Coletti3 , P. Leocata1 1 Anatomia Patologica, Dipartimento di Scienze della Salute, Università<br />

dell’Aquila, L’Aquila, Italia; 2 U.O.C. Anatomia Patologica, P.O. “SS<br />

Filippo e Nicola”, Avezzano (AQ), Italia; 3 U.O.C. Anatomia Patologica<br />

Ospedale Civile “San Salvatore”, L’Aquila, Italia<br />

Background. First described by Carney in 1967, Hyalinizing<br />

Trabecular Tumor (HTT) represents a rare neoplasm. This lesion<br />

has been defined by the WHO Classification of Tumors<br />

of Endocrine Organs as “a rare tumor of follicular cell origin<br />

with a trabecular pattern of growth and marked intratrabecular<br />

hyalinization”.<br />

HTT is of follicular derivation with a characteristic architectural<br />

and histological features, which can mimic that of a Meduallry<br />

Carcinoma or of a Papillary Carcinoma of the thyroid.<br />

Material and methods. We report on a case of a 58-year-old<br />

presented with a thyroid hypercaptant area in a scintigraphic<br />

evaluation performed as a follow-up evaluation for a previous<br />

bladder carcinoma. An ultrasonographic examination of her thyroid<br />

gland revealed the presence of a single, capsulated nodule<br />

of 25 x 13 x 20 mm in-dimension sited in the left thyroid lobe.<br />

The remaining glandular area showed multiple colloidal nodules,<br />

varying in shape and size, compatible with a diagnosis of multinodular<br />

goiter. No regional lymphadenopathy has been detected<br />

and Fine-Needle Aspiration Cytology (FNAC) as been performed<br />

for diagnostic purpose. Cytological examination revealed several<br />

tireocytes, mainly palced in aggregates, presenting mild to moderate<br />

nuclear atypia and pseudoinclusions. On the basis of these<br />

cytologic findings, a Papillary Thy roid Carcinoma (PTC) was<br />

suspected and patient underwent total thyroidectomy.<br />

Reslts. Grossly, a capsulated, whitish nodule of 1,8 cm indiameter<br />

of the left thyroid lobe was detected. Histopathological<br />

features revealed a lesion mainly composed by oval-shaped<br />

tireocytes with irregular nuclei and nuclear grooves and pseudoinclusions,<br />

within a prominent hyalinizing trabecular pattern.<br />

The remaining thyroid gland consisted of numerous moderately<br />

sized thyroid follicles and some lymphoid follicles with germinal<br />

centers. The tumor cells exhibited a positivity for Cytokeratin<br />

AE1/AE3 and Tireoglobulin and a negativity for Galectin 3,<br />

Fig. 1. Histological features of the lesion. a: well-circumscribed nodule<br />

within the left lobe (H&E, 2x magnification). B: trabecular growth<br />

pattern with inter and intratrabecular.hyaline deposition (H&E, 10x<br />

magnification).

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