Hamed Poostchi Bonab

Nader Pazyar

Nastaran Ranjbari

Shohreh Rafiee

Vita Derakhshandeh

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218 ACTA DERMATOVENEROLOGICA CROATICAActa Dermatovenerol Croat                     2014;22(3):218-220                           LETTER TO THE EDITOR Skin Metastasis as the Initial Manifestation of Poorly Differentiated Thyroid Carcinoma  Dear Editor,    Poorly differentiated thyroid carcinoma (PDTC) is a rare and clinically aggressive thyroid cancer of follicu-lar cell origin. This thyroid tumor can also arise from Hürthle cell or papillary thyroid carcinoma (1). PDTC accounts for 4-7% of all thyroid cancers and it is twice as common in men of a mean age of 55.7 years (1,2). According to the World Health Organization (WHO) definition, PDTC has 2 histomorphologic subtypes: insular and noninsular (1). However, based on clinical features, PDTC has a morphologically and behavior-ally intermediate position between well differenti-ated (follicular and papillary) and undifferentiated (anaplastic) thyroid carcinoma (3,4). Notably, PDTC often presents in an advanced stage and has a pro-pensity for local recurrence,   tending to metastasize to regional lymph nodes, the lungs, and bone (1). Accordingly, this thyroid tumor has a rapid and fatal outcome despite appropriate treatment (3).Skin metastases are a rare phenomenon in PDTC, representing 0.7-2.0% of all cutaneous malignant neoplasms (5). Skin metastasis from thyroid carci-noma is rare and occasionally represents the initial manifestation of an occult thyroid carcinoma (5,6). To the best of our knowledge, only a few cases of cuta-neous metastasis from PDTC have been reported in the English-language literature until 2012. Herein, we report on an additional case of PDTC with metastasis to the skin as a presenting sign of thyroid cancer.A 78-year-old man presented with multiple skin nodules on the scalp, forehead, and chin. The patient presented with a progressive mass on the right side of the thyroid lobe that had developed 3 months previously. The patient had a history of odinophagia, weight loss, and decreased appetite. He had been a smoker for 40 years, but had no familial history of thyroid disease or exposure to radiation. On examina-tion, multiple erythematous and tender nodules were found on the scalp, forehead, and chin (Figure 1). Thy-roid examination revealed both sides of the thyroid gland were enlarged, as well as fixed and firm nod-ules in the right thyroid lobe without any evidence of thyrotoxicosis or hypothyroidism. Additionally, there was a palpable cervical lymphadenopathy on the right side. Routine hematological and biochemi-cal thyroid hormones profile tests were within nor-mal ranges. X-ray of the chest showed multiple foci of calcification on both lungs, but skull X-ray, abdomen ultrasonography, and brain computered tomography (CT) were normal.A thyroid scan revealed a cold nodule in the right lobe of the thyroid gland. A fine needle aspiration of the thyroid nodule was performed, and stained with Papanicolaou stain. Cytology smears revealed a mainly bloody background  with few atypical cells in-dicating a neoplastic process. One of the scalp lesions was excised due to the clinical diagnosis of meta-static skin tumor and adenexal tumor, and submitted for histopathological examination. Histology of the lesion showed normal epidermis with presence of grenz zone between tumoral cells (Figure 2), as well as neoplastic cells arranged in nests within the delicate vascular stroma with minimal nuclear pleomorphic and small, but distinct nucleoli and clear cytoplasms. Additionally, solid nests, trabeculae, and a cribriform arrangement of cells with micro follicle formation and a wide area of necrosis were seen. These findings were consistent with poorly differentiated carcinoma (insular carcinoma). On the other hand, immunohis-tochemical tests were positive for thyroid transcrip-tion factor 1 (TTF-1) and thyroglobulin staining. Although the surgery was a difficult task because of the extensive thyroid metastases of tumor cells, a right-sided thyroid lobectomy and modified radical neck dissection was performed. The patient was dis-219ACTA DERMATOVENEROLOGICA CROATICALetter to the editor Acta Dermatovenerol Croat     2014;22(3):218-220charged from the hospital and referred to the oncol-ogy department for palliative treatment. Follow-up was continued for 4 months after the primary diag-nosis of skin metastases, but he died due to the wide-spread metastases of tumor cells.Thyroid carcinoma metastases to the skin are a rare clinical entity, particularly as a presenting feature of underlying malignancy (5,6). In a recent study that included 3848 patients with metastatic carcinoma, no thyroid neoplasms were observed (7). Dahl et al. reviewed English-language literature since 1964 onwards and found 43 cases of thyroid carcinoma with cutaneous metastases among the 39 patients for whom histological findings of the tumor were reported (7). Papillary neoplasm was most common (41%), followed by follicular (28%), anaplastic (15%), and medullary carcinoma (15%). In that study, thyroid cancer was diagnosed before cutaneous metastasis in most cases, with a single case where cutaneous metastasis preceded the diagnosis of the primary thyroid cancer (7). Thyroid metastatic skin lesions are typically pres-ent as slowly growing erythematous or purple nod-ules that are tender, may be itchy, and can ulcerate (6,8). Studies have shown that the scalp is the most common site, being involved in approximately two thirds of thyroid carcinoma cases (8,9).Immonoperoxidase methods have been used to demonstrate that thyroglobulin, a 670 kd glycopro-tein synthesized in the cytoplasm of follicular thyroid epithelial cells, is present in normal thyroid glands, goiters, thyroiditis, and some thyroid carcinomas. Thyroglobulin is detectable in all cases of follicular carcinoma and 95% of papillary carcinoma but is ab-sent in anaplastic thyroid carcinoma (7).Thyroid transcription factor-1 (TTF–1) is a nucle-ar protein expressed in follicular cells of the thyroid gland and also in lung and brain cells. This factor is a good marker of thyroid differentiation and detection of origin in metastatic carcinomas (1). The sensitiv-ity for thyroglobulin and TTF–1 alone for thyroid tu-mor is 90.5% and 92.9%, respectively, and combined monitoring of the two increases the sensitivity for detection of thyroid carcinoma (10). Survival after the diagnosis of PDTC shows a poor outcome. The mean 5-year survival of affected patients is 71.6% and the 10- year survival rate  is 46.3% (4). In our patient, skin metastases stained positive for TTF–1 and thyroglob-ulin. The tumor was aggressive and led to death 4 months after the initial diagnosis and treatment. In conclusion, we report on one more case of PDTC in an old man with multiple skin metastases. References1.  Bongiovanni M, Bloom L, Krane JF, Baloch ZW , Powers CN, Hintermann S, et al. Cytomorpholo-gic features of poorly differentiated thyroid car-cinoma: A multi-institutional analysis of 40 cases. Cancer Cytopathol 2009;117:185-94.2.  Kini H, Nirupama M, Rau AR, Gupta S, Augustine A. Poorly differentiated (insular) thyroid carcinoma arising in a long-standing colloid goiter: A cytolo-gical dilemma. J Cytol 2012;29:97-9.3.  Bruglia M, Palmonella G, Silvetti F, Rutigliano P, Criante P, Marmorale C, et al. Skin and thigh mus-cle metastasis from papillary thyroid cancer. Sing-apore Med J 2009;50:61-4.Figure 1. Erythematous nodular skin lesion on the scalp skin, completely raised. Figure 2. Metastatic poorly differentiated thyroid car-cinoma; epidermis is intact with presence of a grenz zone between tumoral cells and the epidermis H&E; x 400220 ACTA DERMATOVENEROLOGICA CROATICA4. Asioli S, Erickson LA, Righi A, Jin L, Volante M, Jen-kins S, et al. Poorly differentiated carcinoma of the thyroid: validation of the Turin proposal and analysis of IMP3 expression. Modern Pathology 2010;23:1269-78.5.  Giorgi V, Alfaioli B, Massi D, Wnekowicz E, Sestini S, Papi F, et al. Solitary cutaneous metastasis as the first sign of relapse of thyroid carcinoma: A clini-cal, dermoscopic-pathologic case study. Dermatol surg 2009;35:523-6.6.  Alwaheeb S, Ghazarian D, Boerner SL, Asa SL. Cu-taneous manifestations of thyroid cancer: a report of four cases and review of the literature. J Clin Pathol 2004;57:435-8.7.  Dahl PR, Brodland DG, Goellner JR, Hay ID. Thyroid carcinoma metastatic to the skin: A cutaneous manifestation of a widely disseminated malig-nancy. J Am Acad Dermatol 1997;36:531-7.8.  Chakraborty J, Bandyopadhyay A, Choudhuri MK, Mitra K, Guha D, Mallik MG. Cutaneous metastasis from follicular variant of papillary thyroid carcino-ma: A case diagnosed on cytology. Indian J Pathol Microbiol 2008;51:91-3.9.  Song H-J, Xue Y-L, Xu Y-H, Qiu Z-L, Luo Q-Y. Rare metastases of differentiated thyroid carcino-ma: pictorial review. Endocrine-Related Cancer 2011;18:165-74.10. Ramos-Vara JA, Miller MA, Johnson GC, Pace LW. Immunohistochemical detection of thyroid tran-scription factor-1, thyroglobulin, and calcitonin in canine normal, hyperplastic, and neoplastic thy-roid gland. Vet Pathol 2002;39:480-7.Reza Yaghoobi1, Nastaran Ranjbari1,2, Shohreh Rafiee1, Vita Derakhshandeh3, Hamed Poostchi Bonab3, Nader Pazyar11Department of Dermatology, Ahvaz Jundishapur University of Medical Sciences; 2Department of Pathol-ogy, Ahvaz Jundishapur University of Medical Sciences; 3Department of Otolaryngology, Ahvaz Jundishapour University of Medical Sciences, Ahvaz, IranCorresponding author:Nader Pazyar, MDDepartment of Dermatology Imam Hospital Ahvaz, Irandr.pazyar@gmail.comReceived: February 17, 2013Accepted: May 20, 2014Letter to the editor Acta Dermatovenerol Croat     2014;22(3):218-220

Skin metastasis as the initial manifestation of poorly differentiated thyroid carcinoma

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