HomeLearnCase Presentation

Case Presentation

Case Presentation – May 2025

Breast Ductal Carcinoma Metastasis to the Thyroid

Written by: Kale Kuhlman, Student, Cleveland Clinic Cytology Program, Cleveland, Ohio

Patient Age: 71-year-old female

Specimen Type: Left lobe thyroid FNA, ThinPrep® Non-Gyn slide, Cell block

Patient History: Recent left vocal cord paralysis, significant change on ultrasound, history of invasive ductal breast cancer

Cytologic Diagnosis: Positive for malignant cells, metastatic adenocarcinoma, consistent with breast primary. The tumor cells stained positive for Estrogen Receptor (ER) and GATA3, and stained negative for TTF1, PAX8, and Thyroglobulin on IHC.

Biopsy / Pathologic Diagnosis: Left Breast, 8 o’clock, Skin Punch Biopsy – Infiltrating ductal carcinoma involving dermal lymphatics.

Case provided by: Cleveland Clinic, Cleveland, Ohio

Breast Ductal Carcinoma Metastasis to the Thyroid

Etiology:  

Breast cancer is the most common cancer to occur in women across the globe.1,2 While still possible in men, 1 in 8 women will develop breast cancer.3 Compare this to the statistic that only 1 in 726 men will develop breast cancer.4 Higher estrogen and progesterone stimulation accounts for higher prevalence of breast cancer in women. Genetics is also a major factor that has been linked to increased risk of breast cancer in certain patients. History of breast cancer in the family, particularly a first-degree relative, puts a patient at a higher risk. Most often, hereditary breast cancer is associated with having a mutation in either breast cancer susceptibility gene 1 (BRCA1) or breast cancer susceptibility gene 2 (BRCA 2). Age is another factor for increased risk, mostly mimicking other cancers that have age-related risk due to the cellular mutations over time and age-related increase in carcinogenesis.1 Metastasis to the thyroid, for any cancer, is not a common occurrence.2,5,6 According to the literature, only around 2-3% of all malignant thyroid tumors are secondary tumors.5 It is far more likely for a patient to have a second primary malignancy of the thyroid and primary breast cancer, than to have a breast cancer metastasize to the thyroid.2 While still very uncommon, breast cancer has been seen to metastasize to the thyroid. Among mammary carcinomas, ductal carcinoma more frequently metastasizes than lobular carcinoma. 7,8

Clinical Features:

Commonly, patients with a breast carcinoma metastasis to the thyroid will have a known prior history of a breast primary.6 Patients that have this metastatic cancer in the thyroid usually have diffuse metastatic disease.7 After diagnosing the primary tumor, it can take months to  years before a metastasis is detected.5 Metastatic breast cancer to the thyroid may present in different ways ranging from asymptomatic nodules to symptomatic nodules causing midline neck swelling, dysphonia, dysphagia, hoarseness, and/or pain. 5,6,8 According to the literature, ultrasound imaging of these tumors is variable, presenting as heterogenous and diffuse calcifications without a nodule, a hypoechoic solid nodule, or a hypoechoic solid nodule with nodular goiter.6

Treatment and Prognosis:

Metastatic breast cancer to the thyroid represents distant metastasis. Distant metastasis, or Clinical Stage IV disease, carries a grim prognosis regardless of the organ to which the breast cancer metastasized. Multi-organ metastases lead to worse prognosis, which is seen in around 35-80% of patients who have metastatic cancer in the thyroid.9 When a breast cancer has metastasized to a distant organ, they are all treated in the same manner. Depending on the type of breast cancer, the cancer may be treated with chemotherapy, immunotherapy, or endocrine therapy.10 After systemic therapy, if the cancer is affecting the patient’s quality of life, radiation and surgery may be used.10 The ultimate goal of the treatment is to prolong life and minimize symptoms to improve their quality of living.10  

Cytology:

Metastatic adenocarcinoma of the breast to the thyroid will often present with moderate to high cellularity on a smear.11 Depending on the morphology of the original breast carcinoma, the metastatic cancer will mimic the original. Since breast cancers have many different morphological features, the best thing to do is to pull the original slides of the breast cancer, if possible, in order to compare morphologies. This case in particular showed sheets and clusters of cells with enlarged nuclei that had pale chromatin. Hyperchromasia and anisonucleosis were also visualized. Immunohistochemical (IHC) stains are extremely helpful for this diagnosis. Typical breast stains such as estrogen and progesterone receptors, GATA3, and mammaglobin will help indicate the correct origin. Using thyroid stains such as thyroglobulin, PAX8, calcitonin, and TTF-1, as well as parathyroid stains like parathormone will help to confirm whether the cells are from a thyroid/parathyroid lesion.11

Differential Diagnosis: 

It is important to know what differentials look similar to your tumor in order to correctly diagnose the case, especially when metastatic cancer is a possibility. Since this specimen was taken from the thyroid, it is necessary to rule out primary tumors first. For the cells of infiltrating ductal adenocarcinoma, they are usually greater in size than that of follicular neoplasms.11 There will also be the absence of microfollicles that would point towards a thyroid origin.11 This case presented with sheets and groups with some nuclei showing pseudoinclusions and fairly bland chromatin, so papillary thyroid carcinoma (PTC) had to be considered. PTC is the most prevalent thyroid cancer in the United States, so it is an extremely reasonable consideration. However, PTC usually has nuclei with grooves and a more characteristic “powdery” chromatin pattern that was not seen in this case. While there were sheets and clusters, there were no distinct papillae that would be indicative of PTC. It is worth mentioning that no psammoma bodies were seen either. While these are not always seen in PTC cases, they can be helpful in making a PTC diagnosis. IHC stains such as thyroglobulin, TTF-1, PAX8, and keratins can be used for this differential diagnosis.12

Some cells, specifically on the ThinPrep, were plasmacytoid in appearance. This could be suggestive of medullary thyroid carcinoma (MTC). However, the chromatin is quite different, with “salt and pepper” granular chromatin with inconspicuous nucleoli. The more cohesive groups of cells seen in this case are also uncharacteristic of MTC, where a noncohesive pattern with loose clusters is more common.  MTC can also appear spindled, which was absent. Amyloid is another possible cytologic detail that was missing. For definitive testing, IHC stains like calcitonin, chromogranin, and CEA can be used to differentiate MTC.12

 Metastatic lung adenocarcinoma is another important differential to consider. Both metastatic lung adenocarcinoma and breast adenocarcinoma can have medium to large cells that may present in clusters. Lung adenocarcinomas may present as more columnar with eccentrically placed nuclei that are round to oval. They can also have prominent nucleoli. It is also possible to see intracytoplasmic mucin, which would not be indicative of breast adenocarcinoma. The IHC stains of TTF-1 and Napsin-A being negative would help to rule out this differential.11

 

References:

  1. Admoun C, Mayrovitz HN. The Etiology of Breast Cancer. In: Mayrovitz HN, editor. Breast Cancer [Internet]. Brisbane (AU): Exon Publications; 2022 Aug 6. Chapter 2. https://www.ncbi.nlm.nih.gov/books/NBK583809/doi 10.36255/exon-publications-breast-cancer-etiology Accessed February 21, 2025
  2. Plonczak AM, DiMarco AN, Dina R, Gujral DJ, Palazzo FF. Breast cancer metastases to the thyroid gland – an uncommon sentinel for diffuse metastatic disease: a case report and review of the literature. Journal of Medical Case Reports. 2017;11:269. doi:https://doi.org/10.1186/s13256-017-1441-x
  3. American Cancer Society. Key Statistics for Breast Cancer. American Cancer Society. Published January 12, 2024. https://www.cancer.org/cancer/types/breast-cancer/about/how-common-is-breast-cancer.html. Accessed March 3, 2025.
  4. Key Statistics for Breast Cancer in Men. www.cancer.org. Published January 19, 2024. https://www.cancer.org/cancer/types/breast-cancer-in-men/about/key-statistics.html. Accessed March 3, 2025.
  5. Saini T, Gupta P, Gupta N, Srinivasan R, Saikia UN, Dey P. Fine needle aspiration cytology of metastatic tumours to the thyroid. Cytopathology. Published online February 15, 2023. doi:https://doi.org/10.1111/cyt.13220
  6. Zhou L, Chen L, Xu D, Shao Q, Guo Z, Ge M. Breast cancer metastasis to thyroid: a retrospective analysis. Afri Health Sci.2017;17(4):1035-1043. https://dx.doi.org/10.4314/ahs.v17i4.11
  7. Celik E, Ozturk T, Nilay Sengul Samanci, Demirci NS, Burak Akovali, Fuat Hulusi Demirelli. Breast cancer to thyroid gland: An unconventional metastatic site. Journal of Cancer Research and Therapeutics. 2022;18(3):788-791. doi:https://doi.org/10.4103/jcrt.jcrt_561_20
  8. Ramirez Stieben L, Cecilia Vargas M, Polillo D, Lufft K, Saldias P, Bedini I. Metastasis of Breast Cancer to the Thyroid Gland. MEDICINA (Buenos Aires). (83):741-745. Accessed February 23, 2025. https://www.medicinabuenosaires.com/revistas/vol84-24/n4/741.pdf
  9. Papi G, Guido Fadda, Salvatore Maria Corsello, et al. Metastases to the thyroid gland: prevalence, clinicopathological aspects and prognosis: a 10-year experience. 2007;0(0):070208104737004-??? doi:https://doi.org/10.1111/j.1365-2265.2007.02773.x
  10. Trayes KP, Cokenakes SEH. Breast Cancer Treatment. Am Fam Physician. 2021;104(2):171-178.
  11. Layfield L, Kakudo K, Kholovac I. Metastatic Tumors, Lymphomas, and Rare Tumors of the Thyroid. In: The Bethesda System for Reporting Thyroid Cytopathology. Third Edition. Cham, Switzerland: Springer Nature Switzerland AG; 2023:227-251.
  12. Cibas E. Thyroid. In: Cytology: Diagnostic Principles and Clinical Correlates. Fifth EditionElsevier/Saunders; 2021:288-327

CytologyStuff