Інформація призначена тільки для фахівців сфери охорони здоров'я, осіб,
які мають вищу або середню спеціальну медичну освіту.

Підтвердіть, що Ви є фахівцем у сфері охорони здоров'я.

Мобильная версия

Регистрация Забыли пароль?


Коморбідний ендокринологічний пацієнт

Международный эндокринологический журнал Том 19, №6, 2023

Вернуться к номеру

Нове уявлення про гістопатологічні особливості Warthin-подібної папілярної карциноми щитоподібної залози

Нове уявлення про гістопатологічні особливості Warthin-подібної папілярної карциноми щитоподібної залози

Авторы: V. Hoperia (1), O. Mostiuk (1), A. Dinets (1–3), S. Sheptukha (4), O. Hubar (4), M. Gorobeiko (1, 3)
(1) — Institute of Biology and Medicine, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
(2) — Verum Expert Clinic, Kyiv, Ukraine
(3) — Institute of Healthcare, Kyiv Agrarian University, Kyiv, Ukraine
(4) — State Scientific Institution “Scientific and Practical Center of Preventive and Clinical Medicine” State Administration of Affairs, Kyiv, Ukraine

Рубрики: Эндокринология

Разделы: Клинические исследования

Версия для печати


Резюме

Актуальність. Warthin-подібна папілярна карцинома щитоподібної залози (WLPTC) є рідкісним варіантом папілярного раку щитоподібної залози, що вважається підтипом онкоцитарного варіанта. Мета дослідження: представити діагностичні та клінічні особливості, онкологічне та хірургічне лікування пацієнтів із WLPTC, а також їх обговорення порiвняно з іншими дослідженнями. Матеріали та методи. У цій роботі проаналізовано випадок WLPTC, поєднаної з тирео­їдитом Хашимото, в 31-річної жінки. Результати. Пацієнтку госпіталізували з приводу вузла щитоподібної залози. При ультразвуковому дослідженні в лівій частці щитоподібної залози виявлено утворення овальної форми розміром 24 мм з неправильними контурами. Виконано тонкоголкову аспіраційну пункційну біопсію цього вузла і встановлено діагноз папілярного раку щитоподібної залози. Хворій проведено тиреоїдектомію, двосторонню модифіковану та центральну дисекцію шиї, лімфаденектомію. При патогістологічному дослідженні виявлено WLPTC на тлі хронічного тиреоїдиту з метастазами в лімфатичні вузли 2, 3, 4 ліворуч і 6 колекторів шиї. Пацієнтці проведено після­операційну абляцію йодом-131. Висновки. WLPTC є нещодавно описаним варіантом папілярної карциноми щитоподібної залози, який часто асоціюється з лімфоцитарним тиреоїдитом. Правильні цитологічні та гістоморфологічні ознаки є надзвичайно важливими при встановленні діагнозу WLPTC для кращого лікування. Хірургічне та післяопераційне лікування ідентично такому при класичному диференційованому раку щитоподібної залози, має сприятливий результат завдяки низькій частоті рецидивів. Хірургічне лікування повинно включати тирео­їдектомію та дисекцію центрального відділу шиї, а також латеральну дисекцію у випадках підозри на метастази в лімфатичних вузлах або доопераційно підтверджених метастазів.

Background. The Warthin-like variant of papillary thyroid carcinoma (WLPTC) is a rare papillary thyroid carcinoma that is considered to be a subtype of the oncocytic variant. Purpose of the study: to present the diagnostic and clinical features, the oncological and surgical management of a patient with WLPTC as well as its discussion with other relevant studies. Materials and methods. We report a case of Warthin-like papillary thyroid carcinoma in a 31-year-old woman with Hashimoto thyroiditis. Results. The patient was admitted to the hospital with the presence of a node in the thyroid gland. Thyroid ultrasound showed a 24-mm nodule with oval shape and irregular contours in the left lobe. A fine-needle aspiration biopsy was performed, and a diagnosis of papillary thyroid carcinoma was made. The patient underwent thyroidectomy, bilateral modified and central neck dissection, lymphadenectomy. Histopathological examination suggested a WLPTC coexisting with chronic thyroiditis, metastases to the lymph nodes 2, 3, 4 on the left and 6 neck compartments. The patient underwent postoperative I131 ablation therapy. Conclusions. WLPTC is a recently described variant of papillary thyroid cancer that is frequently associated with lymphocytic thyroiditis. The correct cytological and histomorphological features are of utmost importance to render the diagnosis of WLPTC for better management. A surgical and postoperative treatment is identical to that in classic differentiated thyroid cancer, having a favorable outcome due to a low recurrence rate. A surgical management should be thyroidectomy and dissection of central neck compartment as well as lateral dissection in cases of suspicions for metastases in the lymph nodes or metastases confirmed preoperatively by a fine-needle aspiration biopsy.


Ключевые слова

Warthin-подібний варіант папілярної карциноми щитоподібної залози; папілярна карцинома щитоподібної залози; щитоподібна залоза; рідкісна злоякісна пухлина щитоподібної залози

Warthin-like variant of papillary thyroid carcinoma; papillary thyroid carcinoma; thyroid gland; rare thyroid malignancy

doi: http://dx.doi.org/10.22141/2224-0721.19.6.2023.1311

Introduction

Papillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid gland [1]. Approximately 15 histological variants of PTC have been described with various a biological behavior and prognosis [2, 3].
The Warthin-like variant of papillary thyroid carcinoma (WLPTC) is an uncommon and poorly understood tumor with approximately 80 cases reported in literature to date [4, 5], characterized by papillae lined by large oncocytic cells with cores having dense lymphoplasmacytic infiltrate [1, 6].
WLPTC was described in 1995 by Apel et al., who noticed in their series of 13 cases morphological resemblance to Warthin’s tumor of salivary glands origin [7]. The prognosis of WLPTC is the same or less aggressive than that of classical PTC [8–13].
The purpose of this study was to evaluate a WLPTC in a 31-year-old woman with a history of chronic thyroiditis. We aimed to present the diagnostic and clinical features as well as the oncological and surgical management of patient with WLPTC as well as its discussion with other relevant studies.

Materials and methods

A 31-year-old woman was admitted to department o surgery with chief complaints of the presence of a painless no–dule in the thyroid gland. Hypothyroidism was detected and levothyroxine was prescribed at an initial dose of 125 μg/day (thyroid stimulating hormone (TSH) level 4.3 μIU/ml) with a gradual increase to 150 μg/day (TSH level 2.23 μIU/ml).
Ultrasound examination of the neck showed left thyroid lobe with hypoechoic nodule of 24 mm in greatest diameter, oval in shape, with irregular contours, vertical orientation (Thyroid Imaging Reporting and Data System 4). Ultrasound also showed features of the chronic thyroiditis such as heterogeneous echostructure of thyroid parenchyma due to presence of hydrophilic and fibrous-modified areas. The volume of the right lobe was 6.2 cm3 and the left lobe was 7.3 cm3. The capsule of the thyroid gland is not thickened.

Results

Fine needle aspiration biopsy (FNAB) showed a 24-mm left thyroid nodule with evidence of papillary thyroid carcinoma. A tumor composed of papillae lined by Hurthle cells having an abundant amount of granular eosinophilic cytoplasm and nuclear clearing and grooving with intranuclear cytoplasmic inclusions. The stalk of papillae showed dense lymphoplasmacytic infiltrate. Furthermore, the gland was affected by chronic lymphocytic thyroiditis (Fig. 1).
The patient underwent a total thyroidectomy as well as bilateral modified and central compartments neck dissection were performed. Histopathological analysis of the specimen confirmed the presence of PTC coexisting with chronic thyroiditis, as well as metastases to the lymph nodes of 2, 3, 4 on the left neck compartments and to the central neck compartment. The histopathology revelated a TNM for the patient as pT1bN1bM0, stage I.
At follow up of 6 weeks after the surgery, ultrasound examination of the thyroid bed and lymph nodes of the neck showed no signs of metastatic changes to the cervical lymph nodes. The level of plasma thyroglobulin was less than 0.04 ng/mL, thyroglobulin antibody (TgAb) 107 IU/ml (normal range < 0.4 IU/ml), TSH > 100 mIU/l. Considering the high risk of the PTC, the patient underwent radioactive iodine ablation therapy by I131.
It is worth to mention, that scintigraphy did not show areas of pathological accumulation of I131 neither in thyroid bed, nor in other body locations. At follow up of one year, the level of plasma thyroglobulin was less than 0.04 ng/ml, TgAb < 0.4 IU/ml (normal range < 0.4 IU/ml), TSH 0.08 mIU/l, as well as neck ultrasound showed no suspicious lymph nodes, indicating disease-free status. The study was performed in accordance using methodology that we described earlier [14–16].

Discussion

In this report we have showed a rare case of WLPTC. This variant of PTC was presented in 1995 by Apel et al. as papillary Hurthle cell carcinoma of the thyroid with lymphocytic stroma Warthin-like tumor of the thyroid [7]. To our best knowledge, WLPTC represents a rare variant of PTC, with approximately eighty cases have been reported in literature to date [7, 11, 12]. From the historical point of view, it is important to note that Apel et al. chose the name Warthin-like tumor due to its histological resemblance to the Warthin tumor of the salivary gland [7].
The prevalence of WLPTC ranges from 0.2 to 1.9 % of all PTCs, which may be due to misclassification into oncocytic, classical or tall cell variants, or share some features of chronic lymphocytic thyroiditis [17–19]. WLPTC typically represents a tumor with a fast-growing feature as compared to classic PTC, and it is manly diagnosed in females. However, patients diagnosed with WLPTC share similar demographic and clinical characteristics to those affected by PTC [9, 14, 20].
The macroscopic appearance of WLPTC is generally presented as white greyish, unencapsulated, well circumscribed nodule, and confined to the thyroid gland. It may contain hemorrhagic areas and zones of cystic transformations. The tumor size varies in range from 1.5 cm (range 0.3 to 5 cm) [21]. To our knowledge, only one paper has reported a WLPTC larger than 5 cm [5]. The color of the remaining thyroid parenchyma ranges from tan to red brownish and a variable number of nodules of different sizes may be present.
The clinical presentation is the same as that for other differentiated thyroid tumors: absence of signs and symptoms when the lesions are single, small, and deep; palpable masses, glandular swelling, and swallowing and/or phonatory altera–tions for larger, superficial, and/or multiple lesions, which is in line with other authors [22]. Signs, symptoms, and alterations in thyroid function related to thyroiditis or goiter may be also present. As showed in published series, features of CT imaging and ultrasound of WLPTC are similar to PTC. FNAB is a gold standard for early diagnosis of PTC and its variants [20, 23].
It is worth to mention the study showing FNAB features of WLPTC by Yousef et al., demonstrating the presence of groups of follicular cells and papillary fragments against a background of lymphocytes and plasma cells, which infiltrate the fibrovascular cores. The nuclear features are that of typical PTC which include enlargement of nucleus, clearing of chromatin, nuclear inclusions and grooves [23].
Though, FNAB might be a cytological challenge, because oncocytic cells might be admixed with lymphocytes, sharing similar characteristics between PTC and chronic lymphocytic thyroiditis [18, 24]. WLPTC is commonly accompanied by chronic lymphocytic thyroiditis in up to 80 % of all WLPTC cases [25]. Jun et al. reported 16 (0.2 %) WLPTC of 8,179 PTCs [18]. Vascular and capsular invasions are rare in WLPTC, in contrast to our study, showing presence of lymphovascular invasion with metastatic lymph nodes.
Differential diagnosis must be conducted with other variants of PTC with similar histopathology, such as Hurthle cell carcinoma and tall cell carcinoma. The Hurthle cell carcinoma usually lacks lymphoplasmacytic infiltrates and is rarely associated with lymphocytic thyroiditis [26]; the tall cell carcinoma is characterized by a papillary structure with elongated oncocytes, more than twice as high as their width, and tumor aggressiveness with more frequent vascular, nodular and capsular invasion [26].
In our case the preoperative diagnosis based on FNAB was PTC (category TBRST 6) and thyroiditis, which is in line with the current guidelines [23, 27]. The role of immunohistoche–mistry in differential diagnosis with Hurthle cell and tall cell carcinomas is limited. We did not apply immunohistochemical investigation, because of limited laboratory resources which is common for Ukraine [27]. We hypothesized that the biological course of WLPTC might be similar to or even have a better prognosis than classic PTC due to association with benign thyroid disorder such as chronic lymphocytic thyroiditis as showed in our previous reports and other published series [27]. Lam et al. described a case of a 74-year-old Chinese woman diagnosed with a 3.5-cm WLPTC [28]. In this interesting case, Lam et al. presented a description of refusing any treatment by the patients at baseline, followed by palliative thyroidectomy after health worsened, and lethal outcome 15 months after the surgery. This case seems to have involved the natural evolution of thyroid carcinoma from well-differentiated to poorly diffe–rentiated entity with areas of WLPTC that remained untreated for a long time, rather than a typical WLPTC.
The most reliable explanation for the excellent prognosis, low rates of nodal involvement and a low recurrence rate in WLPTC is the presence of lymphatic tissue within the tumor, which seems to contrast and restrain neoplastic progression and dedifferentiation as suggested in published reports [28, 29].
The therapeutic plan for patients with WLPTC must be assessed after surgery. As the biological course of WLPTC is comparable to that of PTC, postoperative management should also be similar. Both ultrasound and ultrasound gui–ded FNAB are excellent for the early diagnosis of primary tumor as well as for assessing cervical lymph nodes involvement, showed in this report, and in further planning of an appropriate management. The appropriate management for the WLPTC with lymph node metastases is thyroidectomy and dissection of neck compartments, followed by radioiodine ablation, suppressive TSH therapy and clinical surveillance every 6 months, which is in line with guidelines and our experience [27, 30, 31].

Conclusions

Warthin-like papillary thyroid carcinoma is a rare variant of PTC, which is frequently accompanied by chronic lymphocytic thyroiditis. Histopathologically, WLPTC resembles Warthin tumors of the salivary glands, with T and B lymphocytes infiltrating the stalks of papillae lined with oncocytic cells. A careful preoperative investigation should include ultrasound investigation of neck compartments to detect early signs of metastases to locoregional lymph nodes. A surgical management should be thyroidectomy and dissection of central neck compartment as well as lateral dissection in cases of suspicions for metastases lymph nodes or preoperatively confirmed metastases by FNAB.
 
 
Received 25.05.2023
Revised 02.08.2023
Accepted 04.09.2023

Список литературы

  1. Christofer Juhlin C., Mete O., Baloch Z.W. The 2022 WHO classification of thyroid tumors: novel concepts in nomenclature and grading. Endocr. Relat. Cancer. 2022 Dec 22. 30(2). e220293. doi: 10.1530/ERC-22-0293.
  2. Zhou J., Wang W.R., Zhang H.F., Gao Q.Q., Wang W.B. et al. Molecular and clinical features of papillary thyroid cancer in adult patients with a non-classical phenotype. Front. Endocrinol. (Lausanne). 2023 Apr 12. 14. 1138100. doi: 10.3389/fendo.2023.1138100.
  3. Cherenko S.M., Larin O.S., Gorobeyko M.B., Sichynava R.M. Clinical analysis of thyroid cancer in adult patients exposed to ionizing radiation due to the Chernobyl nuclear accident: 5-year comparative investigations based on the results of surgical treatment. World J. Surg. 2004 Nov. 28(11). 1071-4. doi: 10.1007/s00268-004-7561-7.
  4. Bogdanova T.I., Saenko V.A., Hashimoto Y., Hirokawa M., Zur–nadzhy L.Y. et al. Papillary Thyroid Carcinoma in Ukraine After Chernobyl and in Japan After Fukushima: Different Histopathological Scena–rios. Thyroid. 2021 Sep. 31(9). 1322-1334. doi: 10.1089/thy.2020.0308.
  5. Patel A., Klubo-Gwiezdzinska J., Hoperia V., Larin A., Jensen K. et al. BRAF(V600E) mutation analysis from May-Grünwald Giemsa-stained cytological samples as an adjunct in identification of high-risk papillary thyroid carcinoma. Endocr. Pathol. 2011 Dec. 22(4). 195-9. doi: 10.1007/s12022-011-9180-9.
  6. Amico P., Lanzafame S., Li Destri G., Greco P., Caltabiano R. et al. Warthin tumor-like papillary thyroid carcinoma with a minor dedifferentiated component: report of a case with clinicopathologic considera–tions. Case Rep. Med. 2010. 2010. 495281. doi: 10.1155/2010/495281.
  7. Apel R.L., Asa S.L., LiVolsi V.A. Papillary Hürthle cell carcinoma with lymphocytic stroma. “Warthin-like tumor” of the thyroid. Am. J. Surg. Pathol. 1995 Jul. 19(7). 810-4.
  8. Jiang C., Cheng T., Zheng X., Hong S., Liu S. et al. Clinical behaviors of rare variants of papillary thyroid carcinoma are associated with survival: a population-level analysis. Cancer Manag. Res. 2018 Mar 9. 10. 465-472. doi: 10.2147/CMAR.S157823.
  9. Jakešová J., Boháč R., Betlach J. Warthin-like papillary carcinoma: Case report. Cesk. Patol. 2023 Spring. 59(1). 23-25.
  10. Cubero Rego D., Lee H., Boguniewicz A., Jennings T.A. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is rare, benign lesion using modified stringent diagnostic criteria: reclassification and outcome study. Ann. Diagn. Pathol. 2020 Feb. 44. 151439. doi: 10.1016/j.anndiagpath.2019.151439.
  11. Kakudo K., Liu Z., Bychkov A., Jung C.K. Nuclear Features of Papillary Thyroid Carcinoma (BRAF-like Tumors), Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (RAS-like Tumors), and Follicular Adenoma/Follicular Thyroid Carcinoma (RAS-like Tumors). Thyroid FNA Cytology: Differential Diagnoses and Pitfalls. 2019. 173-9.
  12. Olmos R., Muñoz F., Donoso F., López J., Bruera M.J. et al. Warthin-like and classic papillary thyroid cancer have similar clinical presentation and prognosis. Arch. Endocrinol. Metab. 2021 May 18. 64(5). 542-547. doi: 10.20945/2359-3997000000270.
  13. Kumar T., Nigam J.S., Tewari P., Jha C.K. Warthin-Like Variant of Papillary Thyroid Carcinoma: An Uncommon Variant. Cureus. 2020 Dec 28. 12(12). e12350. doi: 10.7759/cureus.12350.
  14. Gorobeiko M., Zdorna V., Dinets A. Positive effect of vitamin D supplementation on weight loss in obese patients treated with glucagon-like peptide 1 and lifestyle interventions. Mìžnarodnij endokrinologìčnij žurnal (Ukraine). 2022. 18(5). 278-284. doi: 10.22141/2224-0721.18.5.2022.1186.
  15. Gorobeiko M., Dinets A. Unexpected mapping of recurrent laryngeal nerve by fluorescence-guided surgery using near-infrared indocyanine green angiography. Mìžnarodnij endokrinologìčnij žurnal (Ukraine). 2023. 19(5). 349-53. doi: 10.22141/2224-0721.19.5.2023.1298.
  16. Gorobeiko M., Dinets A., Pominchuk D., Abdalla K., Prylutskyy Y., Hoperia V. Challenges of Differential Diagnosis Between Primary Hyperparathyroidism and Bone Metastases of Breast Cancer. Clin. Med. Insights Case Rep. 2022 Sep 20. 15. 11795476221125136. doi: 10.1177/11795476221125136.
  17. Sahoo P.K., Patnayak R., Khan P.A., Jena A. Warthin-like variant of Papillary thyroid carcinoma — case report of an uncommon tumour with review of literature. Int. J. Surg. Case Rep. 2020. 77. 9-11. doi: 10.1016/j.ijscr.2020.10.058.
  18. Jun H.H., Kim S.M., Hong S.W., Lee Y.S., Chang H.S., Park C.S. Warthin-like variant of papillary thyroid carcinoma: single institution experience. ANZ J. Surg. 2016 Jun. 86(6). 492-4. doi: 10.1111/ans.12725.
  19. Hirokawa M., Nishihara E., Takada N., Higuchi M., Kotakemori M. et al. Warthin-like papillary thyroid carcinoma with immunoglobulin G4-positive plasma cells possibly related to Hashimoto’s thyroiditis. Endocr. J. 2018 Feb 26. 65(2). 175-180. doi: 10.1507/endocrj.EJ17-0319.
  20. Dinets A., Gorobeiko M., Hoperia V., Lovin A., Tarasenko S. Papillary thyroid carcinoma coexisting with benign thyroid and parathyroid pathology: clinical and pathomorphological features. Mìžna–rodnij endokrinologìčnij žurnal (Ukraine). 2023. 19(4). 274-8. doi: 10.22141/2224-0721.19.4.2023.1285.
  21. Valderrabano P., Khazai L., Thompson Z.J., Otto K.J., Hallanger-Johnson J.E. et al. Association of Tumor Size with Histologic and Clinical Outcomes Among Patients With Cytologically Indeterminate Thyroid Nodules. JAMA Otolaryngol. Head Neck Surg. 2018. 144(9). 788-95.
  22. Yeo M.K., Bae J.S., Lee S., Kim M.H., Lim D.J. et al. The Warthin-Like Variant of Papillary Thyroid Carcinoma: A Comparison with Classic Type in the Patients with Coexisting Hashimoto’s Thyroiditis. Int. J. Endocrinol. 2015. 2015. 456027. doi: 10.1155/2015/456027.
  23. Yousef O., Dichard A., Bocklage T. Aspiration cytology features of the warthin tumor-like variant of papillary thyroid carcinoma. A report of two cases. Acta Cytol. 1997 Jul-Aug. 41(4 Suppl.). 1361-8. doi: 10.1159/000333538.
  24. Bullock M.J., Jiang X.S. Top Ten Oncocytic Head and Neck Lesions to Contemplate. Head Neck Pathol. 2023 Mar. 17(1). 53-65. doi: 10.1007/s12105-022-01520-y.
  25. Wong K.S., Higgins S.E., Marqusee E., Nehs M.A., Angell T., Barletta J.A. Tall Cell Variant of Papillary Thyroid Carcinoma: Impact of Change in WHO Definition and Molecular Analysis. Endocr. Pathol. 2019 Mar. 30(1). 43-48. doi: 10.1007/s12022-018-9561-4.
  26. Usenko O.Y., Khomenko I.P., Kovalenko A.Y., Halochka I.P., Andreieshchev S.A. et al. Surgical management of thyroid di–sease. Clinical and practical recommendations. The Ukrainian Journal of Clinical Surgery. 2022. 89(9–10). 41-82. doi: 10.26779/2522-1396.2022.9-10.41.
  27. Dinets A., Nykytiuk O., Gorobeiko M., Barabanchyk O., Khrol N. Milestones and pitfalls in strategic planning of healthcare in capital city in transition. Georgian Med. News. 2021. 315. 189-95.
  28. Lam K.Y., Lo C.Y., Wei W.I. Warthin tumor-like variant of papillary thyroid carcinoma: a case with dedifferentiation (anaplastic changes) and aggressive biological behavior. Endocr. Pathol. 2005 Spring. 16(1). 83-9. doi: 10.1385/ep:16:1:083.
  29. Ulisse S., Baldini E., Lauro A., Pironi D., Tripodi D. et al. Papillary Thyroid Cancer Prognosis: An Evolving Field. Cancers (Basel). 2021 Nov 7. 13(21). 5567. doi: 10.3390/cancers13215567.
  30. Cipriani N.A. Prognostic Parameters in Differentiated Thyroid Carcinomas. Surg. Pathol. Clin. 2019 Dec. 12(4). 883-900. doi: 10.1016/j.path.2019.07.001.
  31. Haugen B.R. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Diffe–rentiated Thyroid Cancer: what is new and what has changed? Cancer. 2017 Feb 1. 123(3). 372-381. doi: 10.1002/cncr.30360.

Вернуться к номеру