|Year : 2018 | Volume
| Issue : 3 | Page : 142-146
A rare incidental case of an occult breast carcinoma micrometastasis in papillary thyroid carcinoma: A view within a view
Jasmine Kaur1, Sonam Sharma2, Tejinder Singh Bhasin3, Ranjan Agarwal4, Rahul Mannan3
1 Department of Oral and Maxillo-Facial Surgery, Sri Guru Ram Das Institute of Dental Sciences and Research, Amritsar, Punjab, India
2 Department of Pathology, Kalpana Chawla Government Medical College, Karnal, Haryana, India
3 Department of Pathology, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab, India
4 Department of Pathology, Rohilkhand Medical College and Hospital, Bareilly, Uttar Pradesh, India
|Date of Web Publication||15-Nov-2018|
Dr. Sonam Sharma
Department of Pathology, Kalpana Chawla Government Medical College, Karnal, Haryana
Source of Support: None, Conflict of Interest: None
Metastasis to thyroid gland is rare, accounting for only 2%–3% of malignant lesions of thyroid and if present, is associated with a poor prognosis. Herein, we describe a case of a 42-year-old female who presented initially with papillary carcinoma of the thyroid and a synchronous malignancy was pointed toward on the basis of a secondary population of atypical cells in intrathyroidal as well as perithyroidal blood vessels emboli. Immunohistochemistry and systematic review of the patient later proved the micrometastasis to be that of carcinoma breast for which the patient was operated 6 years ago. The present case is worth reporting because it documents the presence of two different cancers in a single-organ system (a rare presentation of breast ductal cancer metastasizing to the papillary thyroid carcinoma) by the means of an important yet overlooked lymphovascular compartment, by the identification of the metastatic tumor emboli.
Keywords: Breast carcinoma, lymphovascular, metastasis, papillary thyroid carcinoma, synchronous
|How to cite this article:|
Kaur J, Sharma S, Bhasin TS, Agarwal R, Mannan R. A rare incidental case of an occult breast carcinoma micrometastasis in papillary thyroid carcinoma: A view within a view. Thyroid Res Pract 2018;15:142-6
|How to cite this URL:|
Kaur J, Sharma S, Bhasin TS, Agarwal R, Mannan R. A rare incidental case of an occult breast carcinoma micrometastasis in papillary thyroid carcinoma: A view within a view. Thyroid Res Pract [serial online] 2018 [cited 2018 Dec 10];15:142-6. Available from: http://www.thetrp.net/text.asp?2018/15/3/142/245562
| Introduction|| |
The incidence of breast cancer is increasing worldwide and it is expected to be the most common malignancy in Indian females by the year 2020.,, Breast cancer is often screened early because of the availability of good diagnostic tools along with reasonably fine quality of neo-adjuvants, latest surgical procedures, and postoperative management, leading to an increased disease-free survival in many females. However, distant and local recurrences remain a challenge despite an extensive treatment plan. The most common sites for carcinoma breast metastasis are lung, liver, brain, and bone. Thyroid cancers like breast cancer also carry a good prognosis and lower rate of recurrence in comparison to other malignancies, but their incidence has been gradually increasing for the last two decades due to the availability of ultrasonography and fine-needle aspiration cytology (FNAC), as tools to screen and diagnose various thyroid lesions.,,, Metastasis to thyroid gland is rare and accounts for only 2%–3% of malignant lesions of the thyroid gland. Metastasis in an organ system is usually identifiable due to the presence of islands, groups, or singly scattered tumor tissue of the primary tumor and a second population of cells not native to that organ system. Herein, we report a case of a 42-year-old female who presented initially with papillary thyroid carcinoma and a synchronous malignancy was pointed toward due to the presence of a secondary population of atypical cells in intrathyroidal as well as perithyroidal blood vessels emboli. Immunohistochemistry (IHC) and systematic review of the patient later proved the micrometastasis to be that of carcinoma breast for which the patient was operated 6 years ago.
| Case Report|| |
A 42-year-old female presented to the otolaryngology outpatient department with a swelling in the midline of the neck for the last 1 month. On local examination, the swelling was 3.5 cm × 3 cm in size, firm in consistency, nontender, and it moved on deglutination. The overlying skin was unremarkable. Ultrasonography showed a solitary mass of 4 cm × 3 cm within the right thyroid lobe having an irregular outline and exhibiting small punctuate regions of echogenecity representing microcalcifications. FNAC was suggested to rule out papillary carcinoma of the thyroid. The FNAC smears revealed cellular aspirate with monolayered sheets of cells showing papillary architecture. Individual cells were large showing overlapping of nuclei and irregular contours. Intranuclear inclusions and grooves with pale finely granular cytoplasm and multiple micronucleoli were seen. Multinucleated cells and gummy colloid were also evident. Hence, a cytological diagnosis consistent with the radiological diagnosis of papillary thyroid carcinoma was made. The patient's hematological, biochemical, serological, and thyroid function tests were within normal limits. The patient underwent hemithyroidectomy along with Level IV lymph node dissection. On gross examination, a nodular-to-ill-circumscribed, grayish white, fleshy growth in the upper pole of the right thyroid measuring 5.2 cm × 3.8 cm in size was noted [Figure 1]. Multiple pieces were processed from the representative areas. The microscopy showed a partially circumscribed and an encapsulated nodule, composed of tumor cells which were arranged as follicles and forming focal papillae at many places. Individual tumor cells exhibited nuclear overlapping, nuclear grooves, nuclear membrane irregularities, and pseudoinclusions. All these features were those of papillary carcinoma of the thyroid [Figure 2]a. However, in addition to the above findings, it was noted that a tumor of different morphology was present in the intrathyroidal and perithyroidal blood vessels. These cells had hyperchromatic, pleomorphic nuclei showing irregular nuclear membrane with the presence of nucleoli in some. The cytoplasm was scant and basophilic in appearance. The nuclear and cytoplasmic morphology appeared to be different from the nuclei of the papillary thyroid carcinoma. The patient was recalled and a detailed clinical history was taken again. The patient revealed that she had a previous mastectomy for infiltrating ductal carcinoma of the left breast which was done 6 years back followed by chemotherapy and radiotherapy. Her annual follow-up a few months back was unremarkable, but since last 1 month, the thyroid nodule had appeared for which the patient has presented herself now. Thus, on account of the significant past surgical history and aberrant histomorphology, a double pathology was suspected and IHC was advised to find out the nature of these cells. On IHC, thyroid cells were positive for thyroglobulin [Figure 2]b, but the tumor emboli were positive for estrogen receptor, GATA 3, human epidermal growth factor receptor 2 (Her-2/neu), Bcl-2, cytokeratin 5/6, Ki-67, and epidermal growth factor receptor (EGFR) while it was negative for progesterone receptor, suggesting a metastasis from breast carcinoma [Figure 3] and [Figure 4]. On the basis of all these findings, a final diagnosis of synchronous papillary thyroid carcinoma with vascular micrometastasis of residual breast ductal carcinoma to thyroid was rendered. Mammography of the unaffected breast was unremarkable and the operated scar site was healthy. No nodule, discharge, or abnormality was evident on palpation. The patient was referred to higher apex center for proper oncological workup and therapeutics.
|Figure 1: Resected thyroid gland on cut section showing a grayish white growth|
Click here to view
|Figure 2: (a) Tumor cells arranged in papillae showing nuclear overlapping, nuclear grooves, and pseudoinclusions (H and E, ×200) (b) Thyroglobulin immunoreactivity of the tumor cells (immunohistochemistry, ×100)|
Click here to view
|Figure 3: Vascular tumor emboli exhibiting (a) Focal positivity for cytokeratin 5/6 (immunohistochemistry, ×200) (b) Strong positive immunoreaction for Bcl-2 (immunohistochemistry, ×400) (c) Weak positivity for EGFR (immunohistochemistry, ×400) (d) Strong positivity for GATA 3 (immunohistochemistry, ×100)|
Click here to view
|Figure 4: Breast carcinoma cells showing (a) estrogen receptor positivity (immunohistochemistry, ×400) (b) Negative immunoexpression for progesterone receptor (immunohistochemistry, ×400) (c) Her-2/neu positivity, Score 3+ (immunohistochemistry, ×400) (d) Ki-67 positivity in 80% cells (immunohistochemistry, ×400)|
Click here to view
| Discussion|| |
Although breast and thyroid cancer are increasingly common malignancies in women and thyroid gland itself shows metastasis from other organs and systems, the synchronous presence of both papillary thyroid carcinoma and ductal carcinoma breast is very rare. Extensive search in literature reveals the presence of such a scenario in three cases, with all the previous cases being reported from the Far East Asian countries.,, Till date, no such case has been reported from India and that too with such an unusual pathological presentation of a second tumor which only presents as micrometastasis in vessels with no proper intraparenchymal deposits.
Genesis of the synchronous tumor, especially in case of breast and thyroid cancer, is a subject of great debate. A clear association between the two has been documented by various researchers through sonographic screening for thyroid cancer in females undergoing breast ultrasonography, who have shown significant higher risk of developing thyroid lesions in breast cancer and vice versa., It is also postulated that a patient with either thyroid or breast cancer may have an elevated chance of developing other cancer. The USA National Cancer Institute Data have shown that the incidence of thyroid cancer is higher in patients with preexisting malignancy than in patients without preexisting malignancy.
It is now accepted that the usage of radiotherapy against any cancer may predispose a patient to the risk of a second malignancy. Papillary carcinoma of the thyroid gland has a strong association with radioisotopes and radiation tumorigenesis which might be the case in patients of breast cancer who are given routine postoperative radiotherapy. Genetic aberrations, especially p53 mutations and similar hormonal influences on both the organs, have also been implicated as an important attributable factor in synchronous thyroid and breast cancers., Nevertheless, numerous significant advances have been made on the molecular level to identify various possible determinants leading to the development of synchronous breast and thyroid malignancies. Current areas of interest are focused on the role of thyroid hormone and associated oncogenes such as sodium iodide symporter in case of thyroid and overexpressed (amplified) nuclear protein 1, retinoid-inducible nuclear factor, and nuclear receptor co-activator in the breast tissue as the shared candidates for tumor oncogenesis in thyroid and breast cancers.,, Therefore, a pathologist as well as the dealing physician should be aware of not only a secondary cancer when following up a primary cancer case, but also a synchronous cancer, in case of evaluating papillary thyroid carcinoma or breast ductal carcinoma, such as in the present case.
Lymphovascular invasion is the spread of neoplasia through blood vessels and lymphatics. This finding especially in carcinomas is reported toward the spread to regional lymph nodes that drain the tissue in which tumor arose. Extensive search has been done to find out the prognostic significance of lymphovascular invasion in various types of cancer, especially breast, urothelial, and colorectal cancers.,, Documenting a lymphovascular invasion cannot be overstarted in all types of neoplasia settings. Despite this, a search for lymphovascular invasion is often not scrutinized carefully, until the bulk of tumor tissue is identified or regional lymph node metastasis is seen. In the present case, on careful examination of vascular channels of the parent tissue component of the tumor, a second population of neoplastic cells was identified, leading eventually to the diagnosis of lymphovascular micrometastasis of residual tumor tissue of breast cancer in a preexisting papillary thyroid carcinoma. This case is unique in its pathological presentation as unlike the previously reported cases which have documented the presence of two sets of tumor tissue, i.e., papillary carcinoma of the thyroid and ductal carcinoma of the breast, the only evidence of breast cancer was in intrathyroidal and perithyroidal blood vessels and no other evidence of this malignancy in other organ system was elicited, thus emphasizing a great importance in a thorough and diligent examination of vascular elements outside the tumor tissue even in the normal appearing surrounding parenchyma.
The management of patients with thyroid metastasis from breast cancer is a challenging task as most of the thyroid metastasis cases are asymptomatic and are identified because of the appearance of single or multiple masses. The accuracy of FNAC and ultrasonography in such cases is also controversial as the secondary tumor may evade its detection by these modalities and the cases may be misdiagnosed.,, In our case too, breast cancer metastasis in the thyroid gland was missed on both these techniques. Therefore, it is recommended that a comprehensive medical history and meticulous clinical examination along with histopathological assessment of surgically resected thyroid specimen followed by IHC are essential in clinching a definite diagnosis in such a milieu.
The therapeutic approach in such cases still remains questionable as there are no defined verdicts regarding the effects of surgery, chemotherapy, and radiotherapy. However, few researchers have documented that isolated thyroidectomy can be used as an option for local disease control so as to palliate and prevent the potential morbidity of tumor extension., Nevertheless, the outcome in metastatic thyroid disease tends to be poor since it is a reflection of systemic dissemination of a primary tumor.,
| Conclusion|| |
The concept of synchronous primary malignancies should always be kept in the mind while dealing with the cases of metastatic disease. A high index of suspicion, proper clinical evaluation of the patients, histopathology with emphasis on the identification of metastatic tumor emboli in the lymphovascular compartment, and IHC plays a pivotal role in establishing a concrete diagnosis in such an uncommon setting. Newer elaborative genetic and hormonal studies along with cumulative data of such reports are required for better insight in synchronous occurrence of breast ductal carcinoma within a papillary thyroid carcinoma in the near future.
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.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Shetty P. India faces growing breast cancer epidemic. Lancet 2012;379:992-3.
Sharma S, Rana BP. Giant fibroadenoma of breast: A diagnostic dilemma in a middle aged woman. Adv Cytol Pathol 2017;2:109-12.
Sharma S, Sonali. Cutaneous metastasis from an asymptomatic breast cancer masquerading as an infected sebaceous cyst. Madridge J Dermtol Res 2018;3:46-50.
Chen AY, Levy L, Goepfert H, Brown BW, Spitz MR, Vassilopoulou-Sellin R, et al.
The development of breast carcinoma in women with thyroid carcinoma. Cancer 2001;92:225-31.
Liu L, Shi J, Mao F, Wei J, Fu D, Zhang J, et al.
Synchronous primary cancers of the thyroid and breast: A case report and review of the literature. Oncol Lett 2015;9:351-4.
Bhasin TS, Mannan R, Manjari M, Mehra M, Gill Sekhon AK, Chandey M, et al.
Reproducibility of 'the Bethesda system for reporting thyroid cytopathology': A multicenter study with review of the literature. J Clin Diagn Res 2013;7:1051-4.
Sharma S, Mandal D, Yadav AK, Mandal AK. Primary thyroid lymphoma: A comprehensive summary of two cases. Int J Sci Rep 2015;1:177-80.
Mannan R, Piplani S, Sharma S, Manjari M, Gupta S. Cytological correlation of spectrum of head and neck lesions with epidemiological and diagnostic parameters. Indian J Pathol Oncol 2017;4:92-7.
Zhong J, Lei J, Jiang K, Li Z, Gong R, Zhu J, et al.
Synchronous papillary thyroid carcinoma and breast ductal carcinoma: A rare case report and literature review. Medicine (Baltimore) 2017;96:e6114.
Wang CC, Shen WL, Lee HH, Tsao CJ, Huang WS, Huang WT. Thyroid cancer presenting with concomitant metastatic breast cancer in the thyroid. J Cancer Res Pract 2014;1:248-53.
Park JS, Oh KK, Kim EK, Chang HS, Hong SW. Sonographic screening for thyroid cancer in females undergoing breast sonography. AJR Am J Roentgenol 2006;186:1025-8.
Park JS, Oh KK, Kim EK, Son EJ, Chang HS, Hong SW, et al.
Sonographic detection of thyroid cancer in breast cancer patients. Yonsei Med J 2007;48:63-8.
Sharma S, Chintamani, Khambra P, Mandal AK. Synchronous oral and breast malignancies: A rare presentation. Indian J Surg Oncol 2017;8:426-9.
Van Fossen VL, Wilhelm SM, Eaton JL, McHenry CR. Association of thyroid, breast and renal cell cancer: A population-based study of the prevalence of second malignancies. Ann Surg Oncol 2013;20:1341-7.
Simon MS, Tang MT, Bernstein L, Norman SA, Weiss L, Burkman RT, et al.
Do thyroid disorders increase the risk of breast cancer? Cancer Epidemiol Biomarkers Prev 2002;11:1574-8.
Ghosh S, Rao PB, Sarkar S, Kotne S, Turlapati SP, Mishra A, et al.
A rare case of a synchronous anaplastic carcinoma thyroid with ductal carcinoma breast. Case Rep Oncol Med 2014;2014:468159.
Gaertner FC, Rohde F, Mueller J, Blechert B, Janssen KP, Essler M, et al.
Endogenous expression of the sodium iodide symporter mediates uptake of iodide in murine models of colorectal carcinoma. Int J Cancer 2009;125:2783-91.
Smith VE, Franklyn JA, McCabe CJ. Expression and function of the novel proto-oncogene PBF in thyroid cancer: A new target for augmenting radioiodine uptake. J Endocrinol 2011;210:157-63.
Han JS, Molberg KH, Sarode V. Predictors of invasion and axillary lymph node metastasis in patients with a core biopsy diagnosis of ductal carcinoma in situ
: An analysis of 255 cases. Breast J 2011;17:223-9.
Cheng L, Montironi R, Davidson DD, Lopez-Beltran A. Staging and reporting of urothelial carcinoma of the urinary bladder. Mod Pathol 2009;22 Suppl 2:S70-95.
Lim SB, Yu CS, Jang SJ, Kim TW, Kim JH, Kim JC, et al
. Prognostic significance of lymphovascular invasion in sporadic colorectal cancer. Dis Colon Rectum 2010;53:377-84.
Yang SI, Park KK, Kim JH. Thyroid metastasis from breast carcinoma accompanied by papillary thyroid carcinoma. Case Rep Oncol 2014;7:528-33.
Plonczak AM, DiMarco AN, Dina R, Gujral DM, Palazzo FF. Breast cancer metastases to the thyroid gland – An uncommon sentinel for diffuse metastatic disease: A case report and review of the literature. J Med Case Rep 2017;11:269.
Lacka K, Breborowicz D, Uliasz A, Teresiak M. Thyroid metastases from a breast cancer diagnosed by fine-needle aspiration biopsy. Case report and overview of the literature. Exp Oncol 2012;34:129-33.
Chen H, Nicol TL, Udelsman R. Clinically significant, isolated metastatic disease to the thyroid gland. World J Surg 1999;23:177-80.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]