“Black Ink” Sonographic Pattern as a Predictor for Invasive Papillary Thyroid Micro Carcinoma: A Case Report

Main Article Content

Ersilio Trapanese
Basilio Angrisani
Alberto Angrisani
Ermanno D’Arco
Mariano Agrusta
Carmine De Bartolomeis
Stefano Laudati
Giulio Tarro


Background: This study investigated the utility of the Sonographic pattern "Black Ink" with BRAF mutation testing of thyroid fine-needle aspiration cytology specimens for the risk papillary thyroid microcarcinoma (PTMC).

Case Presentation: We describe a case of a 41-year-old Caucasian woman affected by a ultrasonography “Black Ink” papillary thyroid microcarcinoma (PTMC) of the left lobe of the thyroid gland with very tiny size (Ø 0.4 cm). The characteristics, with the Diagnostic Imaging using Ultrasonography (US), Superb Micro-Vascular Imaging (SMI), fine-needle-aspiration cytology (FNAC) and mutation analysis are here discussed. There are more rare subtypes of thyroid cancer as papillary microcarcinoma "Black Ink" that even if small, are invasive and there is why the need to early diagnosis to avoid their aggressive behavior is needed. Nowadays, focusing on the size, the cut-off for non-occult tiny tumors has dropped to 0.3 cm. This value is of great relevance.

Conclusion: Ultrasonography, FNAC and BRAF molecular study have proven to be the most sensitive diagnostic combination for the early detection of thyroid cancer. Despite the size of this micro-lesion, the Black Ink ultrasonographic pattern associated with malignant cytology at FNAC represents an important biological risk factor and could still be a predictor of the PTMC and risk for neck lymph node metastases.

Ultrasonography, superb micro-vascular imaging, papillary thyroid micro carcinoma, black ink sonographic pattern, BRAFV600E

Article Details

How to Cite
Trapanese, E., Angrisani, B., Angrisani, A., D’Arco, E., Agrusta, M., Bartolomeis, C. D., Laudati, S., & Tarro, G. (2019). “Black Ink” Sonographic Pattern as a Predictor for Invasive Papillary Thyroid Micro Carcinoma: A Case Report. Journal of Advances in Medicine and Medical Research, 30(1), 1-13. https://doi.org/10.9734/jammr/2019/v30i130162
Case Report


Howlader N, Noone AM, Krapcho M, Miller D, Bishop K, Altekruse SF, et al. SEER cancer statistics review, 1975–2013. National Cancer Institute; 2016.

Chen AY, Jemal A, Ward EM. Increasing incidence of differentiated thyroid cancer in the United States, 1988– 2005. Cancer. 2009;115:3801–7.

Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973–2002. JAMA. 2006;295:2164–7.

Lombardi CP, Bellantone R, De Crea C, Paladino NC, Fadda G, Salvatori M, et al. Papillary thyroid micro carcinoma: Extra thyroidal extension, lymph node metastases, and risk factors for recurrence in a high prevalence of goiter area. World J Surg. 2010;34:1214–21.

Lim YC, Choi EC, Yoon YH, Kim EH, Koo BS. Central lymph node metastases in unilateral papillary thyroid micro carcinoma. Br J Surg. 2009;96:253–7.

Schlumberger MJ. Papillary and follicular thyroid carcinoma. N Engl J Med. 1998;338(5):297–306.

Strate SM, Lee EL, Childers JH. Occult papillary carcinoma of the thyroid with distant metastases. Cancer. 1984;54(6): 1093-100.

Woolner LB, Lemmon ML, Beahrs OH, Black BM, Keating R. Occult papillary carcinoma of the thyroid gland a study of 140 cases observed over a 30-year period. J Clin Endocrinol. 1960;2089-105.

Gikas PW, Labow SS, Di Giulio W, Finger JE. Occult metastasis from occult papillary carcinoma of the thyroid. Cancer. 1967;20(12):2100-4.

Roh JL, Park JY, Rha KS, Park CI. Central neck dissection necessary for the treatment of lateral cervical nodal recurrence of papillary thyroid carcinoma? Head & Neck. 2007;29(10):901–6.

Lastra RR, LiVolsi VA, Baloch ZW. Aggressive variant of follicular cell-derived thyroid carcinomas: A cytopathologist’s perspective. Cancer Cytopathol. 2014; 122(7):484-503.

Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics. CA Cancer J Clin. 2014;64(1):9–29.

Sherman SI. Thyroid carcinoma. Lancet. 2003;361(9356):501-11.

Trapanese E, Agrusta M, D’Arco E, Tarro G. Insidious rare thyroid microcarcinoma "Black Ink". Indian Journal of Applied Research. 2017;7(6):67.

Trapanese E, De Bartolomeis C, Angrisani B, Tarro G. Papillary thyroid micro carcinoma (Black Ink). Oncotarget. 2018;29275-29283.

Cao J, Chen C, Chen C, Wang QL, Ge MH. Clinic pathological features and prognosis of familial papillary thyroid micro carcinoma – a large – scale, matched, case-control study. Clinical Endocrinology. 2015;84: 598-606.

Sampson RJ, Key CR, Buncher CR, Lima S. Thyroid carcinoma in Hiroshima and Nagasaki. Prevalence of thyroid carcinoma in autopsy. JAMA. 1969;209(1):65-70.

Li QS, Chen SH, Xiong HH, Xu HH, Li ZZ, Guo GQ. Papillary thyroid carcinoma on sonography. Clin Imaging. 2010;34:121–126.

Kim GR, Kim MH, Moon HJ, Chung WY, Kwak JY, Kim EK. Sonographic characteristics suggesting papillary thyroid carcinoma according to nodule size. Ann Surg Oncol. 2013;20:906–913.

Lu R, Meng Y, Zhang Y, Zhao W, Wang X, Jin M, et al. Superb microvascular imaging (SMI) compared with conventional ultrasound for evaluating thyroid nodule. BMC Med Imaging. 2017;17(1):65.

Berker D, Aydin Y, Ustun I, Gul K, Tutuncu Y, Isik S, et al. The value of fine -needle aspiration biopsy in sub centimeter thyroid nodules. Thyroid. 2008;18:603–608.

Morlan J, Baker J, Sinicropi D. Mutation detection by real-time PCR: A simple, robust and highly selective method. PLoS One. 2009;4(2):e4584.

Park AY, Son EJ, Kim JA, Youk JH, Park YJ, Park CS, et al. Associations of the BRAF (V600E) mutation with sonographic features and clinic pathologic characteristics in a large population with conventional papillary thyroid carcinoma. PLoS One. 2014;9:e110868.

Arora N, Turbendian HK, Kato MA, Moo TA, Zarnegar R, Fahey TJ. Papillary thyroid carcinoma and micro carcinoma: Is there a need to distinguish the two? Thyroid. 2009;19(5):473-7.

Kasai N, Sakamoto A. New subgrouping of small thyroid carcinomas. Cancer. 1987;60(8):1767-70.

Tuttle RM, Haddad RI, Ball DW, Byrd D, Dickson P, Duh QY, Ehya H, et al. Thyroid carcinoma, version 2. J Natl Compr Canc Netw. 2014;12:1671–80.

Hunt JP, Buchmann LO, Wang L, Abraham D. An analysis of factors predicting lateral cervical nodal metastases in papillary carcinoma of the thyroid. Arch Otolaryngol Head Neck Surg. 2011;137:1141–1145.

Zhang L, Wei WJ, Ji QH, Zhu YX, Wang ZY, Wang Y, et al. Risk factors for neck nodal metastasis in papillary thyroid micro carcinoma: A study of 1066 patients. J Clin Endocrinal Metab. 2012;97:1250-1257.

Gu W, Yan H, Luo Y, Wang F, Yang G, Guo Q, et al. Characterization of papillary thyroid micro carcinomas using sonographic features in malignant papillary thyroid cancer: A retrospective analysis. Tian. C, Ed. Medicine. 2015;94(21):841.

Folkman J. Tumor angiogenesis: Therapeutic implications. N Engl J Med. 1971;285:1182–1186.

Machado P, Segal S, Lyshchik A, Forsberg F. Novel microvascular flow technique: Initial results in thyroids. Ultrasound Q. 2016;32(1):67-74.

Kong J, Li JC, Wang HY, Wang YH, Zhao RN, Zhao Y. Role of superb micro-vascular imaging in the preoperative evaluation of thyroid nodules: Comparison with power doppler flow imaging. J Ultrasound Med. 2017;36(7):1329-1337.

Lim YC, Choi EC, Yoon YH, Kim EH, Koo BS. Central lymph node metastases in unilateral papillary thyroid micro carcinoma. Br J Surg. 2009;96(3):253-7.

Zhang L, Wei WJ, Ji QH, Zhu YX, Whang ZY, Whang Y. Risk factors for neck nodal metastasis in papillary thyroid micro carcinoma: A study of 1066 patients. J Clin Endocrinal Metab. 2012;97:1250-57.

Chang YW, Kim HS, Kim HY, Lee JB, Bae JW, Son GS. Should central lymph node dissection be considered for all papillary thyroid micro carcinoma. Asian J Surg. 2015;02.006.

Wang M, Wu WD, Chou SL, Dai XM, Xu JM, Peng ZH. Could tumor size be a predictor for papillary thyroid micro carcinoma: A retrospective cohort study. Asian Pac J Cancer Prev. 2015;16(18): 8625-8.

Noguchi S, Yamashita H, Murakami N, Nakayama I, Toda M, Kawamoto H. Small carcinomas of the thyroid. A long-term follow-up of 867 patients. Arch Surg. 1996;131(2):187-91.

Zhao C, Jiang W, Gao Y, Niu W, Zhang X, Xin L. Risk factors for lymph node metastasis (LNM) in patients with papillary thyroid micro carcinoma (PTMC): Role of preoperative ultrasound. J Int Med Res. 2017;45(3):1221-1230.

Nardi F, Basolo F, Crescenzi A, Fadda G, Frasoldati A, Orlandi F, et al. Italian consensus for the classification and reporting of thyroid cytology. J Endocrinal Invest. 2014;37(6):593-9.

Cibas ES, Ali SZ. The Bethesda system for reporting thyroid cytopathology. Thyroid. 2009;19(11):1159-65.

Xing M. BRAF mutation in papillary thyroid cancer: pathogenic role, molecular bases, and clinical implications. Endocr Rev. 2007;28:742–62.

Elisei R, Ugolini C, Viola D, Lupi C, Biagini A, Giannini R. BRAF (V600E) mutation and outcome of patients with papillary thyroid carcinoma: A 15-year median follow-up study. J Clin Endocrinal Metab. 2008;93: 3943–9.

Shangguan R, Hu YP, Huang J, Yang SJ, Ye L, Lin RX, et al. Association between BRAFV600E mutation and the American college of radiology thyroid imaging, reporting and data system in solitary thyroid carcinoma. Acad Radiol. 2018;05-010.

Ming Zhao Xing. BRAF V600E mutation in papillary thyroid micro carcinoma: The promise of better risk management. Ann Surg Oncol. 2009;16(4):801-803.

Lee X, Gao M, Ji Y, Feng Y, Li Y, Zhang Y. et al. Analysis of differential BRAF(V600E) mutational status in high aggressive papillary thyroid micro carcinoma. Ann Surg Oncol. 2008;16(2):240-5.

Lin KL, Wang OC, Zhang XH, Dai XX, Xu XQ, Qu JM. The BRAF mutation is predictive of aggressive clinic pathological characteristics in papillary thyroid micro carcinoma. Ann Surg Onocol. 2010;17: 3924–3930.

Yokozawa T, Miyauchi A, Kuma K, Sugawara M. Accurate and simple method of diagnosing thyroid nodules the modified technique of ultrasound-guided fine needle aspiration biopsy. Thyroid. 1995;5:141–45.

Ahuja S, Ernst H, Lenz K. Papillary thyroid carcinoma: Occurrence and types of lymph node metastases. J Endocrinal Invest. 1991;14:543–49.

Lee J, Rhee Y, Lee S, Ahn CW, Cha BS, Kim KR. Frequent, aggressive behaviors of thyroid micro carcinomas in Korean patients. Endocrine Journal. 2006;53(5): 667-632.

Page C, Biet A, Boute P, Cuvelier P, Strunski V. Aggressive papillary thyroid micro carcinoma. Eur Arch Otorhinolaryngology. 2009;266(12):1959-63.

Hay ID, Grant CS, Taylor WF, McConahey WM. Ipsilateral lobar resection versus bilateral lobar resection in papillary thyroid carcinoma: a retrospective analysis of surgical outcome using a new prognostic score system. Surgery. 1987;102(6):1088-95.

Kuo EJ, Thy WJ, Zheng F, Zanocco KA, Livhits MJ, Yeh MW. Individualizing surgery in papillary thyroid carcinoma based on a detailed sonographic assessment of extrathyroidal extension. Thyroid. 2017; 27(12):1544-1549.

Price AK, Randle RW, Schneider DF, Sippel RS, Pitt SC. papillary thyroid micro carcinoma: decision- making, extent of surgery and outcomes. J. Surg Res. 2017;218:237-245.

Cox C, Bosley M, Southerland LB, Ahmadi S, Perkins J, Roman S, et al. Lobectomy for treatment of differentiated thyroid cancer: Can patients avoid postoperative thyroid hormone supplementation and be compliant with the American Thyroid Association Guidlines? Surgery. 2018; 163(1):75-80.

Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, et al. The Eighth Edition AJCC cancer staging manual: Continuing to build a bridge from a population based to a more “personalized” approach to cancer staging. CA Cancer J Clin. 2017;67(2):93-99.

Hedinger C, Williams ED, Sobin LH. The WHO histological classification of thyroid tumors: A commentary on the second edition. Cancer. 1989;63(5):908-11.

Rosai J, Carangiu ML, DeLellis RA. Tumors of the thyroid gland. Atlas of tumorpathology. Armed Forces Institute of Pathology. The Journal of Pathology; 1993.

Kuo EJ, Goffredo P, Sosa JA, Roman SA. Aggressive variants of papillary thyroid micro carcinoma are associated with extra thyroidal spread and lymph node metastases: a population-level analysis. Thyroid. 2013;23(10):1305–1311.

Hefer TH, Joachims HZ, Hashinonai M, Bem- Arieh Y, Brown J. Highly aggressive behavior of occult papillary thyroid carcinoma. J Laryngol Otol. 1995;109(11): 1109-12.

Gupta S, Ajise O, Duitz L, Wang B, Nonaka D, Ogilvie J, et al. Follicular variant of papillary thyroid cancer: Encapsulated, no encapsulated, and diffuse: Distinct biologic and clinical entities. Arch Otolaryngology Head Neck Surg. 2012;138(3):227-33.

Yamamoto Y, Maeda T, Izumi K, Otsuka K. Occult papillary carcinoma of the thyroid. A study of 408 autopsy cases. Cancer. 1990;65:1173-1179.

Gong Y, Li G, Lei J,You J, Jiang K, Li Z, et al. A favorable tumor size to define papillary thyroid micro carcinoma: An analysis of 1176 consecutive cases. Cancer Manag Res. 2018;10:899-906.

Rodolico V, Cabibi D, Pizzolanti G, Richiusa P, Gebbia N, Martorana A, et al. BRAF (V600E) mutation and p27 (kip1) expression in papillary carcinomas of the thyroid =1 cm and their paired lymph node metastases. Cancer. 2007;110:1218–26.

Lupi C, Giannini R, Ugolini C, Proietti A, Berti P, Minuto M, et al. Association of BRAF V600E mutation with poor clinic pathological outcomes in 500 consecutive cases of papillary thyroid carcinoma. J Clin Endocrinal Metab. 2007;92:4085–90.