52
Correspondence
2. Trillo AA, Accettullo LM, Yeiter TL. Choriocarcinoma of the esophagus: histologic and cytologic findings. A case report. Acta Cytol 1979;23:69–74. 3. Craig ID, Shum DT, Desrosiers P et al. Choriocarcinoma metastatic to the lung A cytologic study with identification of human choriogonadotropin with an immunoperoxidase technique. Acta Cytol 1983;27:647–50. 4. Choi HJ, Park IA. Fine needle aspiration cytology of metastatic choriocarcinoma presenting as a breast lump. A case report. Acta Cytol 2004;48:91–4. 5. Santiago Casiano M, Paulo Malave LM, Fahme E et al. Unusual presentation of primary gastric choriocarcinoma in a 24-year-old female patient. Bol Asoc Med P R 2011;103:77–9. 6. Shibuya T, Osada T, Kodani T et al. Gastrointestinal hemorrhage as the first manifestation of metastatic extragonadal choriocarcinoma. Intern Med 2009;48:551–4.
Pre-operative cytodiagnosis of follicular thyroid carcinoma with mandibular metastasis presenting as gingival swelling DOI:10.1111/cyt.12120
Dear Editor, A solitary thyroid nodule manifesting as a follicular-patterned lesion on fine needle aspiration cytology (FNAC) can be an adenomatous nodule, adenoma, follicular thyroid carcinoma (FTC) or follicular variant of papillary thyroid carcinoma (FVPTC).1,2 Clinically, if a solitary thyroid nodule exhibiting a follicular pattern on cytology presents with a suspicious metastatic focus, the differential diagnosis naturally narrows down to FTC and FVPTC. As the initial pattern of metastasis varies between these two tumours; in selective instances, clinicoradiological presentation, in combination with simple cytomorphological assessment, may play a decisive diagnostic role. We report a case supporting our statement. A 70-year-old woman presented with a solitary thyroid nodule and a swelling in the oral cavity of 1 month duration. Both swellings were firm. The thyroid nodule measuring 4 9 2 cm2 was freely mobile, whereas the gingival swelling involving the left side of the floor of the mouth measured 5 9 4 cm2. X-Ray revealed lytic lesions in the mandible (Figure 1a). Both swellings were subjected to FNAC. The thyroid aspirate was haemorrhagic, whereas the gingival Correspondence: N. Siddaraju, Department of Pathology, JIPMER, Pondicherry, India. Tel.: +919944426595; Fax: (0413) - 38067 37381; E-mail: [email protected]:
aspirate was scanty with rare tiny whitish particles. May–Gr€ unwald–Giemsa (MGG)- and Papanicolaou (Pap)-stained smears were examined. The thyroid aspirate was highly cellular with discrete microfollicles, as well as clusters (Figure 1b), together with many enlarged naked nuclei displaying evenly distributed coarse chromatin. Some individual follicles were entangled in blood clot. No colloid or nuclear features of papillary thyroid carcinoma (PTC) were appreciated. The gingival aspirate was comparatively less cellular, but showed similar cells exhibiting a follicular pattern (Figure 1c with inset). By correlating the cytomorphological features (indicative of follicular neoplasm on both thyroid and gingival aspirates) with the lytic lesion in the mandible, a definitive diagnosis of ‘FTC with mandibular metastasis and soft tissue involvement’ was given. Subsequently, the patient underwent total thyroidectomy followed by medical management. Histological examination of the thyroidectomy specimen confirmed the diagnosis of FTC with frank capsular invasion. Immunohistochemistry (IHC) using antibodies to galectin-3 and CK-19 was negative in the main tumour area, with galectin-3 positivity seen in the infiltrating margin. Owing to subtle morphological differences and difficulty in assessing the presence or absence of an invasive nature, it is difficult to distinguish between a follicular adenoma and well-differentiated FTC on cytology alone.1,2 Poorly differentiated carcinoma can be recognized cytologically but most authors agree on the inability of cytology to distinguish welldifferentiated FTC from other cellular follicular lesions. Maruta et al.3 claimed that features such as nuclear atypia, high NC ratio and coarse chromatin could indicate malignancy in some follicular-patterned lesions.3 FVPTC is a close cytological differential diagnosis to FTC. A high cell yield and microfollicular pattern with nuclear features of PTC, such as large ovoid nuclei, powdery chromatin, nuclear grooving and intranuclear cytoplasmic inclusions, are useful in diagnosing FVPTC.1,2 Cytological evaluation is not just morphology oriented, but, with an appropriate clinical background, it has the potential to provide a precise diagnosis. Clinically, FTC is associated with early haematogenous metastasis to distant sites, whereas PTC is characterized by an initial lymphatic metastasis to cervical lymph nodes.2 When present, this feature can effectively be made use of to differentiate FTC from FVPTC. In the present case, both thyroid and gingival aspirates showed features of a follicular neoplasm lacking nuclear fea© 2013 John Wiley & Sons Ltd Cytopathology 2015, 26, 50–60
Correspondence
(a)
(c)
(b)
Figure 1. (a) X-Ray showing mandibular metastasis from follicular thyroid carcinoma. (b) Cellular thyroid aspirate showing a prominent microfollicular pattern (Papanicolaou 9400). (c) Gingival aspirate showing neoplastic cells with microfollicular pattern (May–Gr€ unwald–Giemsa 9200); inset (9400) shows magnified view of neoplastic follicular cells.
tures of PTC, which prompted a definitive diagnosis of FTC. The other features favouring FTC in our case included the absence of colloid, coarse nuclear chromatin and the clinical evidence of lytic lesions in the mandible indicative of bony metastasis in the absence of nodal involvement. The role of IHC in follicular-patterned thyroid neoplasms is debated. However, CK-19, galactin-3 and HBME-1 are potential markers of thyroid malignancy, but do not distinguish rare FTCs from FAs.4 Most studies have stressed the importance of IHC in distinguishing benign versus malignant, rather than in identifying a specific follicular lesion. One of our recent studies showed galectin-3 positivity in the infiltrating margins of a few of our FTC cases.5 Recently, BRAF mutations have been shown to be highly specific for PTC, but tend to be negative in the follicular variant which concerns us here.6 An early distant metastasis from FTC can occur in sites such as bone, lung, brain, skin and adrenals, and the incidence ranges between 11% and 25%. FTC with soft tissue metastases has also been documented. Their aggressiveness varies widely and metastatic disease is the primary cause of death in patients with FTC. Therapeutic approaches to patients presenting with distant metastasis are well defined. These include total thyroidectomy if the primary tumour can easily be resected, followed by radioactive iodine therapy and suppressive treatment with L-thyroxine.7 A similar approach was followed in the present case. © 2013 John Wiley & Sons Ltd Cytopathology 2015, 26, 50–60
P. Mishra, N. Siddaraju, P. Manivannan, K. Selvi, P. C. Toi and B. A. Badhe Department of Pathology, JIPMER, Pondicherry, India References 1. Ali S, Cibas ES. The Bethesda System for Reporting Thyroid Cytopathology. New York; Dordrecht; Heidelberg; London: Springer; 2010. 2. Kini SR. Thyroid and Parathyroid. In: Color Atlas of Differential Diagnosis in Exfoliative and Aspiration Cytopathology, 2nd edn. Philadelphia, PA: Wolters Kluwer/Lippincott Williams &Wilkins; 2011: pp. 401–542. 3. Maruta J, Hashimoto H, Suehisa Y et al. Improving the diagnostic accuracy of thyroid follicular neoplasms: cytological features in fine-needle aspiration cytology. Diagn Cytopathol 2011;39:28–34. 4. De Matos LL, Del Giglio AB, Matsubayashi CO et al. Expression of CK-19, galectin-3 and HBME-1 in the differentiation of thyroid lesions: systematic review and diagnostic meta-analysis. Diagn Pathol 2012;7:97. 5. Manivannan P, Siddaraju N, Jatia L et al. Role of proangiogenic marker galectin-3 in follicular neoplasms of thyroid. Indian J Biochem Biophys 2012;49:392–4. 6. Rossi ED, Martini M, Capodimonti S et al. BRAF (V600E) mutation analysis on liquid-based cytology-processed aspiration biopsies predicts bilaterality and lymph node involvement in papillary thyroid microcarcinoma. Cancer Cytopathol 2013;121:291–7. 7. Sevinc A, Buyuberber S, Sari R et al. Follicular thyroid cancer presenting initially with soft tissue metastasis. Jpn J Clin Oncol 2000;30:27–9.
53
Copyright of Cytopathology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Correspondence
2. Trillo AA, Accettullo LM, Yeiter TL. Choriocarcinoma of the esophagus: histologic and cytologic findings. A case report. Acta Cytol 1979;23:69–74. 3. Craig ID, Shum DT, Desrosiers P et al. Choriocarcinoma metastatic to the lung A cytologic study with identification of human choriogonadotropin with an immunoperoxidase technique. Acta Cytol 1983;27:647–50. 4. Choi HJ, Park IA. Fine needle aspiration cytology of metastatic choriocarcinoma presenting as a breast lump. A case report. Acta Cytol 2004;48:91–4. 5. Santiago Casiano M, Paulo Malave LM, Fahme E et al. Unusual presentation of primary gastric choriocarcinoma in a 24-year-old female patient. Bol Asoc Med P R 2011;103:77–9. 6. Shibuya T, Osada T, Kodani T et al. Gastrointestinal hemorrhage as the first manifestation of metastatic extragonadal choriocarcinoma. Intern Med 2009;48:551–4.
Pre-operative cytodiagnosis of follicular thyroid carcinoma with mandibular metastasis presenting as gingival swelling DOI:10.1111/cyt.12120
Dear Editor, A solitary thyroid nodule manifesting as a follicular-patterned lesion on fine needle aspiration cytology (FNAC) can be an adenomatous nodule, adenoma, follicular thyroid carcinoma (FTC) or follicular variant of papillary thyroid carcinoma (FVPTC).1,2 Clinically, if a solitary thyroid nodule exhibiting a follicular pattern on cytology presents with a suspicious metastatic focus, the differential diagnosis naturally narrows down to FTC and FVPTC. As the initial pattern of metastasis varies between these two tumours; in selective instances, clinicoradiological presentation, in combination with simple cytomorphological assessment, may play a decisive diagnostic role. We report a case supporting our statement. A 70-year-old woman presented with a solitary thyroid nodule and a swelling in the oral cavity of 1 month duration. Both swellings were firm. The thyroid nodule measuring 4 9 2 cm2 was freely mobile, whereas the gingival swelling involving the left side of the floor of the mouth measured 5 9 4 cm2. X-Ray revealed lytic lesions in the mandible (Figure 1a). Both swellings were subjected to FNAC. The thyroid aspirate was haemorrhagic, whereas the gingival Correspondence: N. Siddaraju, Department of Pathology, JIPMER, Pondicherry, India. Tel.: +919944426595; Fax: (0413) - 38067 37381; E-mail: [email protected]:
aspirate was scanty with rare tiny whitish particles. May–Gr€ unwald–Giemsa (MGG)- and Papanicolaou (Pap)-stained smears were examined. The thyroid aspirate was highly cellular with discrete microfollicles, as well as clusters (Figure 1b), together with many enlarged naked nuclei displaying evenly distributed coarse chromatin. Some individual follicles were entangled in blood clot. No colloid or nuclear features of papillary thyroid carcinoma (PTC) were appreciated. The gingival aspirate was comparatively less cellular, but showed similar cells exhibiting a follicular pattern (Figure 1c with inset). By correlating the cytomorphological features (indicative of follicular neoplasm on both thyroid and gingival aspirates) with the lytic lesion in the mandible, a definitive diagnosis of ‘FTC with mandibular metastasis and soft tissue involvement’ was given. Subsequently, the patient underwent total thyroidectomy followed by medical management. Histological examination of the thyroidectomy specimen confirmed the diagnosis of FTC with frank capsular invasion. Immunohistochemistry (IHC) using antibodies to galectin-3 and CK-19 was negative in the main tumour area, with galectin-3 positivity seen in the infiltrating margin. Owing to subtle morphological differences and difficulty in assessing the presence or absence of an invasive nature, it is difficult to distinguish between a follicular adenoma and well-differentiated FTC on cytology alone.1,2 Poorly differentiated carcinoma can be recognized cytologically but most authors agree on the inability of cytology to distinguish welldifferentiated FTC from other cellular follicular lesions. Maruta et al.3 claimed that features such as nuclear atypia, high NC ratio and coarse chromatin could indicate malignancy in some follicular-patterned lesions.3 FVPTC is a close cytological differential diagnosis to FTC. A high cell yield and microfollicular pattern with nuclear features of PTC, such as large ovoid nuclei, powdery chromatin, nuclear grooving and intranuclear cytoplasmic inclusions, are useful in diagnosing FVPTC.1,2 Cytological evaluation is not just morphology oriented, but, with an appropriate clinical background, it has the potential to provide a precise diagnosis. Clinically, FTC is associated with early haematogenous metastasis to distant sites, whereas PTC is characterized by an initial lymphatic metastasis to cervical lymph nodes.2 When present, this feature can effectively be made use of to differentiate FTC from FVPTC. In the present case, both thyroid and gingival aspirates showed features of a follicular neoplasm lacking nuclear fea© 2013 John Wiley & Sons Ltd Cytopathology 2015, 26, 50–60
Correspondence
(a)
(c)
(b)
Figure 1. (a) X-Ray showing mandibular metastasis from follicular thyroid carcinoma. (b) Cellular thyroid aspirate showing a prominent microfollicular pattern (Papanicolaou 9400). (c) Gingival aspirate showing neoplastic cells with microfollicular pattern (May–Gr€ unwald–Giemsa 9200); inset (9400) shows magnified view of neoplastic follicular cells.
tures of PTC, which prompted a definitive diagnosis of FTC. The other features favouring FTC in our case included the absence of colloid, coarse nuclear chromatin and the clinical evidence of lytic lesions in the mandible indicative of bony metastasis in the absence of nodal involvement. The role of IHC in follicular-patterned thyroid neoplasms is debated. However, CK-19, galactin-3 and HBME-1 are potential markers of thyroid malignancy, but do not distinguish rare FTCs from FAs.4 Most studies have stressed the importance of IHC in distinguishing benign versus malignant, rather than in identifying a specific follicular lesion. One of our recent studies showed galectin-3 positivity in the infiltrating margins of a few of our FTC cases.5 Recently, BRAF mutations have been shown to be highly specific for PTC, but tend to be negative in the follicular variant which concerns us here.6 An early distant metastasis from FTC can occur in sites such as bone, lung, brain, skin and adrenals, and the incidence ranges between 11% and 25%. FTC with soft tissue metastases has also been documented. Their aggressiveness varies widely and metastatic disease is the primary cause of death in patients with FTC. Therapeutic approaches to patients presenting with distant metastasis are well defined. These include total thyroidectomy if the primary tumour can easily be resected, followed by radioactive iodine therapy and suppressive treatment with L-thyroxine.7 A similar approach was followed in the present case. © 2013 John Wiley & Sons Ltd Cytopathology 2015, 26, 50–60
P. Mishra, N. Siddaraju, P. Manivannan, K. Selvi, P. C. Toi and B. A. Badhe Department of Pathology, JIPMER, Pondicherry, India References 1. Ali S, Cibas ES. The Bethesda System for Reporting Thyroid Cytopathology. New York; Dordrecht; Heidelberg; London: Springer; 2010. 2. Kini SR. Thyroid and Parathyroid. In: Color Atlas of Differential Diagnosis in Exfoliative and Aspiration Cytopathology, 2nd edn. Philadelphia, PA: Wolters Kluwer/Lippincott Williams &Wilkins; 2011: pp. 401–542. 3. Maruta J, Hashimoto H, Suehisa Y et al. Improving the diagnostic accuracy of thyroid follicular neoplasms: cytological features in fine-needle aspiration cytology. Diagn Cytopathol 2011;39:28–34. 4. De Matos LL, Del Giglio AB, Matsubayashi CO et al. Expression of CK-19, galectin-3 and HBME-1 in the differentiation of thyroid lesions: systematic review and diagnostic meta-analysis. Diagn Pathol 2012;7:97. 5. Manivannan P, Siddaraju N, Jatia L et al. Role of proangiogenic marker galectin-3 in follicular neoplasms of thyroid. Indian J Biochem Biophys 2012;49:392–4. 6. Rossi ED, Martini M, Capodimonti S et al. BRAF (V600E) mutation analysis on liquid-based cytology-processed aspiration biopsies predicts bilaterality and lymph node involvement in papillary thyroid microcarcinoma. Cancer Cytopathol 2013;121:291–7. 7. Sevinc A, Buyuberber S, Sari R et al. Follicular thyroid cancer presenting initially with soft tissue metastasis. Jpn J Clin Oncol 2000;30:27–9.
53
Copyright of Cytopathology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
