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Year : 2021  |  Volume : 64  |  Issue : 2  |  Page : 358-361
Metastatic hobnail variant of papillary thyroid carcinoma: A diagnostic challenge in cell block preparation

1 Department of Pathology, IMS and SUM Hospital, Bhubaneswar, Odisha, India
2 Department of Oncosurgery, IMS and SUM Hospital, Bhubaneswar, Odisha, India

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Date of Submission15-Apr-2020
Date of Decision02-Oct-2020
Date of Acceptance09-Dec-2020
Date of Web Publication9-Apr-2021


Hobnail variant of papillary thyroid carcinoma (HV-PTC) is an unusual entity recently included in WHO classification of endocrine tumors (2017) and proposed as an aggressive variant of PTC. Compared to patients of classical counterparts, HV-PTC frequently has extrathyroidal extension, exhibits nodal or distant metastasis, and responds poorly to radioiodine treatment, leading to increased mortality. We hereby describe the cytohistological and immunohistochemical features of a metastatic HV-PTC in 55-year-old male, previously diagnosed as poorly differentiated papillary thyroid carcinoma in thyroidectomy specimen. Five years after total thyroidectomy with radical neck dissection the patient presented with gross pleural effusion showing multiple lung parenchymal and pleural based lesions with complete collapse of lung on computed tomography scan. The conventional cytology of pleural fluid showed dyscohesive cells arranged in micropapillary form gave the suggestion of metastatic papillary carcinoma. But the cell block preparation highlighted >30% hobnail cells arranged in micropapillary pattern showing increased atypical mitosis and occasional pseudoinclusions. Supplemented with immunohistochemistry (CK19, TTF-1, and p53), final diagnosis HV-PTC was made.

Keywords: Hobnail, micropapillary, papillary carcinoma, thyroidectomy, pleural effusion

How to cite this article:
Mohapatra D, Naik S, Das P, Agrawala S. Metastatic hobnail variant of papillary thyroid carcinoma: A diagnostic challenge in cell block preparation. Indian J Pathol Microbiol 2021;64:358-61

How to cite this URL:
Mohapatra D, Naik S, Das P, Agrawala S. Metastatic hobnail variant of papillary thyroid carcinoma: A diagnostic challenge in cell block preparation. Indian J Pathol Microbiol [serial online] 2021 [cited 2021 May 16];64:358-61. Available from: https://www.ijpmonline.org/text.asp?2021/64/2/358/313286

   Introduction Top

Papillary thyroid carcinoma (PTC) is the commonest endocrine carcinoma with yearly incidence in United States of America of 13.5 cases/lakh.[1] It is associated with relatively good survival even in metastatic setting.[1] However at the other end of spectrum, some variants of PTC are associated with aggressive behavior (tall cell, columnar, diffuse sclerosing type).[2] Recent WHO classification of Endocrine tumor (4th edition, 2017) has included hobnail variant (HV)-PTC which is moderately differentiated neoplasm with aggressive behavior and significant mortality.[1],[3],[4]

   Case Report Top

A 55-year-old male presented with severe dyspnea and hemoptysis due to complete collapse of lungs. Computed tomography scan of thorax and X-ray chest revealed multiple pleural-based lesion along with a lung parenchymal nodule and massive pleural effusion [Figure 1]a and [Figure 1]b. The patient has a history of total thyroidectomy along with total laryngectomy and bilateral neck lymph node dissection in which a histopathologic diagnosis of PTC with thyroid cartilage involvement showing foci of poorly differentiated carcinoma was made. A total of 5 out of 50 right cervical lymph nodes showed metastatic carcinomatous deposits, whereas 32 lymph nodes retrieved from left cervical region were free of tumor. Thus, a pathologic stage diagnosis of pT4aN1bMx was made. But, as the diagnosis was given 5 years back, no slides or paraffin block were available to review. Positron emission tomography scan done 3 years post-thyroidectomy shows pleural based nodules in both side. 7 months back whole body iodine scan was done which showed no focal abnormal iodine concentration in the thyroid bed. No evidence of iodine avid regional or distant metastatic disease and the findings were in favor of dedifferentiated thyroid malignancy (iodine refractory) in context of previous clinical history.
Figure 1: (a) Computed tomographic scan of thorax showing pleural based nodule, pleural thickening, a lung parenchymal nodule, and pleural effusion, (b) X-ray of chest showing massive pleural effusion

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The pleural fluid on conventional cytology revealed moderately cellular smears composed of tumor cells covering papillae demonstrating apically located nuclei. Soap bubble like nuclear inclusions were present in majority of the cells. The tumor cells were arranged in dyscohesive clusters. Thus, the diagnosis of papillary thyroid carcinoma metastasizing to pleural fluid was rendered. The cell block histology showed neoplastic cells arranged in predominant micropapillary pattern. The cells exhibited moderate nuclear pleomorphism, hyperchromatism, increased atypical mitosis with intranuclear and cytoplasmic inclusion in some. The typical features of PTC (classic variant), such as nuclear grooving, ground glass nuclei, and mitosis, are only occasionally seen. The cytoplasm was abundant eosinophilic with hobnailing in >30% cells. Few foci of psammoma bodies were also seen [Figure 2]. This was supplemented with immunohistochemistry (IHC) panel of TTF-1, Thyroglobulin, PAX8, Napsin-A, Calretinin, CK19 and p53 [Figure 3]. The negativity of calretinin excluded the possibility of malignant mesothelioma. But the positivity of TTF1 and Napsin-A, raising the suspicion of lung adenocarcinoma, was finally excluded with positivity for p53, PAX8, and focal positivity for thyroglobulin as well. Thus, the diagnosis of metastatic HV-PTC was made.
Figure 2: (a) Cytosmear showing syncytial cell cluster, apically placed nuclei (arrowed), inset showing a community border (DiffQuik, 400x); (b) cytosmear showing cell cluster with cytoplasmic inclusion (arrowed) (DiffQuik, 1000x); (c) photomicrograph showing cell block preparation with papillary cores lined by hobnail cells showing eccentric nuclei and abundant eosinophilic cytoplasm (arrowed) (Hematoxylin and eosin, 400x); (d) photomicrograph showing cell block preparation having papillary core with presence of psammoma body (arrowed) (Hematoxylin and eosin, 400x)

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Figure 3: (a) Strong nuclear positivity for PAX8 (IHC, 400x); (b) nuclear positivity for TTF-1 (IHC, 400x); (c) embrane and cytoplasmic positivity for CK-19 (IHC, 400x); (d) nuclear positivity for p-53 (IHC, 400X)

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   Discussion Top

HV-PTC is a rare variant of PTC that comprise of 0.2% to 0.3% of PTC.[4],[5] The diagnosis of this variant has been recently defined by the presence of at least 30% of cells with hobnail features.[1] It has been advocated that with this higher percentage of hobnail/micropapillary features, the tumors are associated with very aggressive behavior.[3],[6] Tumor with 10% hobnail features also carry a poor outcome.[3] Because of the fact that hobnail histology is more consistently observed than micropapillary pattern in such aggressive tumors, thus HV-PTC is preferred designation.[3]

Though HVPTC displays a spectrum of papillary arrangement with predominance of micropapillary structures with hobnail cells, conspicuous nucleoli and intranuclear, cytoplasmic inclusions but the typical nuclear features of papillary thyroid carcinoma is seldom present. HVPTC is associated with aggressive features (old age, lymphovascular invasion, lymph node metastasis, distant metastasis, high stage) along with genetic features of BRAF mutation in 72%, p53 mutation in 56% and h-TERT mutation in 44% but strikingly RET/PTC rearrangement is absent unlike classic variant of PTC.[2] There is lymph node metastasis of 60–75% cases and that of distant spread in 25–40% cases.[5],[7]

The differential diagnosis includes diffuse sclerosing variant of PTC (DS-PTC).[8] However DS-PTC is associated with squamous metaplasia, fibrosis, and abundant psammoma bodies. Medullary thyroid carcinoma with discohesive cells may overlap with cytologic features with HV-PTC. IHC with calcitonin renders a correct diagnosis. Tumors, such as serous and clear cell carcinoma of ovary, micropapillary breast carcinoma, carcinoma colon, and lung micropapillary adenocarcinoma, which are common mimickers of HV-PTC are differentiated on basis of immunohistochemical markers of WT1, PAX8, MUC1, GCDFP-15, CK20, CDX2, and Napsin-A.[9] A study of two cases of HVPTC showed positivity for thyroglobulin, TTF1, PAX8, CK19, and P53.[10] Our study showed positivity for TTF1, CK19, P53, PAX8, and focal positivity for thyroglobulin. This supports the diagnosis of HV-PTC. Because of paucity of the neoplastic material in the cell block further molecular testing could not be done.

The important differential diagnoses in pleural fluid cell block which can cause diagnostic difficulty in HVPTC are lung micropapillary adenocarcinoma, micropapillary breast carcinoma, and clear cell carcinoma of ovary. Because of similarity of histology findings such as micropapillary pattern as well as lined by tall columnar cells exhibiting abundant eosinophilic to clear cytoplasm and apically located hyperchromatic nuclei, some showing intranuclear cytoplasmic inclusion. Though both papillary thyroid carcinoma and lung adenocarcinoma exhibit positivity for TTF1. But, differentiation from lung adenocarcinoma is done on basis of IHC, i.e., negativity for PAX8, Galectin 3, and thyroglobulin. The breast carcinoma is differentiated from the HVPTC based on positivity for GCDFP15 and negativity for TTF1 and thyroglobulin in the former. Similarly, ovarian clear cell carcinoma though show positivity for PAX8 similar to HVPTC, but is negative for TTF1 and thyroglobulin. In addition, the microscopic features of intracytoplasmic hyaline globules are hallmark for clear cell carcinoma of ovary. It is immensely helpful, if we give preoperative cytologic diagnosis correctly in this tumor which will help the surgeon to take the decision regarding the extent of thyroidectomy. The cytohistologic diagnosis is difficult as the typical nuclear feature of PTC is absent in this variant. P53 as a molecular marker will caution the surgeon further to look for the vascular invasion, lymphnode involvement, and metastasis.[6] Some of the series have reported that the metastatic tumors of HV-PTC behave more aggressively and show histologic features of undifferentiated carcinoma than other metastatic PTC and respond poorly to neoadjuvant therapy.[11] Our patient was prescribed tablet Lenvatinib (oral tyrosine kinase inhibitor) to which he responded very well and showed significant clinicoradiological improvement on 6 months follow-up.

   Conclusion Top

Though papillary thyroid carcinoma is the commonest neoplasm of thyroid, HV-PTC is an aggressive and unusual variant not matching to cytology of classical features of papillary carcinoma thyroid. Histopathological diagnosis in cell block play a gold standard though is extremely difficult which needs strong clinicopathological suspicion supplemented by a battery of IHC stains as well as molecular study. The confusion is further aggravated if the tumor is in metastatic site, but certainly is gold standard which in turn helps the oncologist to plan for further institution of therapy.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Rosai J, Albores Saavedra J, Asioli S, Baloch ZW, Bogdanova T, Chen H, et al. Tumours of the thyroid gland. In: Llyod RV, Osamura RY, Klöppel G, Rosai J, editors. WHO Classification of Tumours of Endocrine Organs. 4th ed. IARC: Lyon; 2017.  Back to cited text no. 1
Nath MC, Erickson LA. Aggressive variants of papillary thyroid carcinoma: Hobnail, tall cell, columnar, and solid. Adv Anat Pathol 2018;25:172-9.  Back to cited text no. 2
Asioli S, Erickson LA, Righi A, Lloyd RV. Papillary thyroid carcinoma with hobnail features: Histopathologic criteria to predict aggressive behavior. Hum Pathol 2013;44:320-8.  Back to cited text no. 3
Asioli S, Erickson LA, Sebo TJ, Zhang J, Jin L, Thompson GB, et al. Papillary thyroid carcinoma with prominent hobnail features: A new aggressive variant of moderately differentiated papillary carcinoma. A clinicopathologic, immunohistochemical, and molecular study of eight cases. Am J Surg Pathol 2010;34:44-52.  Back to cited text no. 4
Lee YS, Kim Y, Jeon S, Bae JS, Jung SL, Jung CK. Cytologic, clinicopathologic, and molecular features of papillary thyroid carcinoma with prominent hobnail features: 10 case reports and systematic literature review. Int J Clin Exp Pathol 2015;8:7988-97.  Back to cited text no. 5
Lubitz CC, Economopoulos KP, Pawlak AC, Lynch K, Dias-Santagata D, Faquin WC, et al. Hobnail variant of papillary thyroid carcinoma: An institutional case series and molecular profile. Thyroid 2014;24:958-65.  Back to cited text no. 6
Ambrosi F, Righi A, Ricci C, Erickson LA, Lloyd RV, Asioli S. Hobnail variant of papillary thyroid carcinoma: A literature review. Endocr Pathol 2017;28:293-301.  Back to cited text no. 7
Takagi N, Hirokawa M, Nobuoka Y, Higuchi M, Kuma S, Miyauchi A. Diffuse sclerosing variant of papillary thyroid carcinoma: A study of fine needle aspiration cytology in 20 patients. Cytopathology 2014;25:199-204.  Back to cited text no. 8
Lilo MT, Bishop JA, Ali SZ. Hobnail variant of papillary thyroid carcinoma: A case with an unusual presentation. Diagn Cytopathol 2017;45:754-6.  Back to cited text no. 9
Cameselle-Teijeiro JM, Rodríguez-Pérez I, Celestino R, Eloy C, Piso-Neira M, Abdulkader-Nallib I, et al. Hobnail Variant of Papillary Thyroid Carcinoma: Clinicopathologic and molecular evidence of progression to undifferentiated carcinoma in 2 cases. Am J Surg Pathol 2017;41:854-60.  Back to cited text no. 10
Morandi L, Righi A, Maletta F, Rucci P, Pagni F, Gallo M, et al. Somatic mutation profiling of hobnail variant of papillary thyroid carcinoma. Endocr Relat Cancer 2017;24:107-17.  Back to cited text no. 11

Correspondence Address:
Sujata Naik
Department of Pathology, IMS and SUM Hospital, Bhubaneswar - 751 003, Odisha
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPM.IJPM_381_20

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