Multifocal Medullary and Papillary Thyroid Carcinoma Occurring as a Collision Tumor: A Case Report

Collision tumor is the occurrence of two histologically and morphologically distinct tumors within the same organ with no histological admixture. Collision tumors of the thyroid are extremely rare constituting < 1% of all thyroid tumors. Clinical profiles and pathological features of Medullary thyroid carcinoma (MTC) and Papillary thyroid carcinoma (PTC) presenting as Collision tumors of thyroid, diagnosed between 2009 and 2019, at a tertiary care cancer center were retrospectively analyzed. Collision tumors comprised 4.7% of all MTC cases diagnosed over 10years. A total of 21 cases (11males, 11 females, M:F = 1) were retrieved with the mean age of patients being 45.33years (range 26-77years). More than half of PTCs involved the right lobe of the thyroid (66.6%). About half (53.4%) of MTCs affected the left lobe. Imaging done pre-operatively failed to identify the smaller second tumor in 60% of the cases with both tumours in separate lobes. Pre-operative FNAC showed only MTC in all 8 cases in which it was done. Papillary microcarcinoma (m-PTC) was seen in 85.7% cases, with one case of multifocal m-PTC. MTC (mean size 3.12cm), on an average, was 3 times larger than the PTC (mean size 0.91cm). The histological variants of MTC included-oncocytic (1/21, 4.7%), spindle cell (1/21, 4.7%), epithelial (3/21, 14.2%) and classical (16/21, 76.2%) and of PTC included classic PTC (12/21, 57.14%), Hurthle cell (2/21, 9.52%), tall cell (1/21, 4.76%) and follicular variant of PTC (6/21, 28.57%). The microscopic extrathyroidal extension (ETE) due to MTC and PTC component was 42.8% and 9.5% respectively. Lymph node metastasis was seen in 16 (76.2%) cases; 87.5% (14/16) of which were contributed by MTC, 12.5% (2/16) by PTC alone, and 12.5% (2/16) cases showed metastasis from both MTC and PTC. MTC had a higher stage than PTC in 85.5% of cases. Collision tumors of the thyroid are exceedingly rare, and possibly underdiagnosed due to variation in sampling techniques, especially of the grossly "normal lobe". The low incidence in our cohort is in favor of the "Chance theory" of co-occurrence. This diagnosis is important due to its therapeutic and prognostic implications.

The new 4th edition World Health Organization classification for thyroid tumors, Asian perspectives.

Disclosure: R. Heinrich: None. K. Kaput: None.Background: This case provides valuable teaching points by describing the extremely rare (<1% of all thyroid tumors) presentation of a collision tumor consisting of two histologically distinct forms of thyroid cancer, medullary thyroid cancer and papillary thyroid carcinoma. Preoperative imaging often fails to identify two morphologically different nodules and fine needle aspiration of the nodule often only identifies one type of cancer, as occurred in this case. With each tumor typically having a different stage and prognosis, management often requires consideration of each tumor individually. Case Description: A 37 year old female presenting with a thyroid nodule located in the isthmus, with associated lymphadenopathy, was subsequently found to have a collision tumor consisting of papillary thyroid carcinoma and metastatic medullary thyroid cancer. The patient was initially found to have a thyroid nodule at the age of 22. At the age of 37, a neck ultrasound revealed a thyroid nodule located in the isthmus measuring 17 mm described as solid, hypoechoic with irregular margins. This was associated with an abnormal appearing right lateral neck (level 3) lymph node which notably had an abnormal short-to-long axis ratio and central calcification. Ultrasound-guided fine needle aspiration of the isthmus nodule revealed papillary thyroid carcinoma while the lymph node aspirate was nondiagnostic and negative for thyroglobulin wash. Repeat biopsy of the level three lymph node showed findings consistent with malignancy, favoring medullary thyroid cancer, though there were insufficient cells for diagnosis. Calcitonin and CEA were elevated at 219 pg/mL (reference 0-5 pg/mL) and 4.8 ng/mL (ULN 4.7 ng/mL) respectively. The patient underwent total thyroidectomy, central neck dissection and right lateral neck dissection. Surgical pathology revealed papillary thyroid carcinoma (15 mm, classic subtype) as well as a focus of medullary thyroid cancer (9 mm), both located in the right thyroid lobe and isthmus with disruption of the capsule. Four out of nine lymph nodes in the right central neck, five out of nine in the right lateral neck and one out of fifteen in the left lateral neck were positive for medullary thyroid cancer. The medullary thyroid cancer was staged as PT1aPN1b and the papillary thyroid carcinoma was staged as P1Tb PN0a. The patient had no known family history of multiple endocrine neoplasia syndrome or medullary thyroid cancer. Conclusion: Thyroid collision tumors are often undiagnosed on neck ultrasound and fine needle aspiration and thus the diagnosis may not become apparent until pathology from a surgical resection of a seemingly single thyroid nodule confirms the presence of two distinct tumors. This case provides an example of how collision tumors may not be detected by standard thyroid nodule evaluations but can drastically change how a thyroid nodule is eventually managed.Presentation: Monday, July 14, 2025

Aim This study examined patients with concurrent medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) with the primary objective of identifying factors that can determine the dominant subtype that will dictate recurrence. Materials and methods The cancer registry at our tertiary care referral center was reviewed to identify all patients from 1995 to 2015 who had been diagnosed with both MTC and PTC on initial total thyroidectomy. Patient demographic, pathology, and recurrence data were collected and reviewed. Results Nineteen patients met the inclusion criteria. Seventeen patients had separate foci of MTC and PTC, and two patients had mixed tumors of medullary and follicular or medullary and the follicular variant of PTC. Thirteen patients had a preoperative diagnosis of MTC, and all 13 had MTC as the higher stage tumor on final pathology. Of these, eight patients had recurrent disease, all of which recurred as MTC. In the six patients with concurrent MTC and PTC who did not have MTC as the preoperative diagnosis, the PTC was the higher stage tumor. Only one patient in this group recurred with PTC, none with MTC. No patients have had recurrent disease that was a different subtype from their preoperative diagnosis or the higher stage tumor. Conclusion The concurrent findings of MTC and PTC in the same patient may result in challenging patient counseling, management, and follow-up. In this series of 19 patients with concurrent PTC and MTC, the subtype of recurrence in all 9 patients with recurrent disease was determined by the preoperative diagnosis and higher stage tumor. Clinical significance The incidental discovery of a second subtype of differentiated thyroid cancer should not alter management of the primary tumor. Patients should be treated in accordance with the preoperative diagnosis and higher stage tumor. How to cite this article Beninato T, Kluijfhout WP, Drake FT, Shen WT, Suh I, Duh QY, Clark OH, Gosnell JE. Preoperative Diagnosis predicts Outcomes in Patients with Concurrent Medullary and Papillary Thyroid Carcinoma. World J Endoc Surg 2017;9(3):94-99.

Medullary thyroid cancer (MTC) is a relatively rare thyroid malignancy, constituting a small percentage of all thyroid cancer cases. Even more rare is the occurrence of mixed MTC and papillary thyroid cancer (PTC), found in a very small fraction of MTC cases. These cancers originate from different cell types with distinct developmental origins. The coexistence of MTC and PTC in the same patient raises questions about whether this occurrence is merely coincidental or if there is an underlying genetic link. We present the case of a woman with metastatic mixed MTC and PTC.A 61-year-old woman with a history of Hashimoto's disease was found to have bilateral thyroid nodules; the largest (1.7 cm) was in the right lobe. This nodule met fine needle aspiration (FNA) biopsy criteria and was found to have a follicular neoplasm of undetermined significance. The patient elected to pursue total thyroidectomy instead of lobectomy given the presence of bilateral nodules. Postoperative pathology showed mixed medullary carcinoma (pT3b) and follicular variant papillary thyroid microcarcinoma (pT1a) involving the right lobe with positive anterior and posterior margins and lymphovascular invasion. Preoperative calcitonin was not checked. However, post-thyroidectomy calcitonin was 1599 pg/mL. She underwent central and right lateral neck dissection which showed 27 out of 35 lymph nodes were positive for malignancy. Postoperative calcitonin dropped to 38.7 pg/mL. She then established care in our endocrine clinic. Screening for pheochromocytoma and primary hyperparathyroidism was normal. She underwent external beam radiation of the neck. A year after her initial surgery, her neck ultrasound and computed tomography (CT) studies show no signs of local or distant anatomic recurrence. Her thyroglobulin level remains undetectable, carcinoembryonic antigen (CEA) within normal range, and calcitonin stable at about 20 pg/mL. She is on levothyroxine 100 mcg daily with thyroid-stimulating hormone (TSH) at a suppression goal of <0.1 mIU/L. Mixed PTC and MTC is poorly studied due to its rarity. The origin of these mixed tumors is unclear, but some suggest that they arise from neoplastic changes of remnant multipotent cells in the thyroid. While patients with PTC often have a favorable prognosis following surgical therapy, MTC has a more aggressive course. We suggest monitoring patients like ours for both MTC and PTC, as if present in isolation. Our case highlights the clinical aspects of this condition and our current knowledge of its pathophysiology.

Based on strong research evidence, thyroid nodules in children and teenagers are more likely to be malignant than in adults. Based on strong research evidence, a history of ionizing radiation to the head or neck is an independent risk factor for the development of thyroid malignancies. There is strong research evidence, including a recent meta-analysis, supporting the use of fine-needle aspiration biopsy in the evaluation of all pediatric and adolescent patients presenting with a thyroid nodule. The surgical management and postoperative care of pediatric and adolescent patients who have well-differentiated thyroid carcinomas remains controversial, because the rarity of the disease limits the ability to conduct randomized, prospective research studies. Numerous studies have demonstrated that, despite presenting with more advanced disease, pediatric and adolescent patients with thyroid carcinoma have a higher survival rate than adults. The American Thyroid Association has issued strong evidence-based recommendations for the management of medullary thyroid carcinoma, including RET mutation testing and early prophylactic total thyroidectomy in children with high-risk mutations.

Prophylactic thyroidectomy for medullary thyroid carcinoma in gene carriers of MEN2 syndrome

Introduction and importance:Papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC) are distinct thyroid malignancies with different cellular origins and management strategies. The coexistence of these two cancers within the same thyroid gland, particularly in separate lobes, is rare and presents unique diagnostic and therapeutic challenges. This case highlights the importance of distinguishing between these malignancies to ensure accurate diagnosis and appropriate treatment.Case presentation:A 60-year-old male presented with a progressively enlarging neck mass over 6 months, accompanied by mild discomfort and intermittent dysphagia. Physical examination revealed a firm, fixed mass in the right thyroid lobe. Laboratory tests showed normal thyroid-stimulating hormone, elevated calcitonin (330 pg/mL), and carcinoembryonic antigen (12 ng/mL). Thyroid ultrasound identified a 4.5 cm hypoechoic nodule in the right lobe and a 1.2 cm nodule in the left. Fine needle aspiration cytology confirmed PTC in the right lobe and MTC in the left.Clinical discussion:Total thyroidectomy with central neck dissection was chosen as treatment. Histopathology confirmed classical PTC in the right lobe and MTC in the left, with characteristic amyloid deposition and positive staining for calcitonin and other markers in MTC. RET proto-oncogene mutation testing was negative. The patient received postoperative radioactive iodine therapy and levothyroxine. At six months, there was no evidence of recurrence.Conclusion:The coexistence of PTC and MTC in separate thyroid lobes is a rare occurrence. Accurate cytological, histopathological, and immunohistochemical evaluations are essential for proper diagnosis and management.

Hyalinizing trabecular tumor (HTT) is a rare unique but controversial thyroid neoplasm, characterized by prominent trabecular growth pattern and stromal hyalinization. Whether HTT is a benign tumor or a variant of papillary thyroid carcinoma (PTC) is still unclear. Cytology findings of HTT have been described in few reports. Cytological features of HTT frequently overlap with those of PTC and medullary thyroid carcinoma, which can lead to frequent misdiagnosis. In order to avoid overtreatment like total thyroidectomy, pathologist should be aware of cytological features of HTT. We present a case of 35-year-old female with a right-side thyroid swelling for three years. Fine needle aspiration cytology was performed. According to The Bethesda System for Reporting Thyroid Cytopathology, cytological diagnosis of benign thyroid neoplasm was made. Histopathology of the right thyroidectomy specimen showed HTT. Accurate preoperative diagnosis of HTT requires a very meticulous and cautious approach in the evaluation of cytological features. Trabecular pattern of cells, vague curved nuclear palisading, radiating arrangement of cells around hyaline material, spindled to elongated cells, filamentous cytoplasmic processes with ill-defined cell border and yellow bodies are important diagnostic features of HTT. Nuclear features alone are insufficient for the diagnosis of HTT. Any suspicious cytology of thyroid lesion should follow hemithyroidectomy and histopathological evaluation.

SummaryWe report a rare case of concurrent medullary thyroid cancer (MTC) and papillary thyroid cancer (PTC) with intermixed disease in several of the lymph node (LN) metastases in a patient who was subsequently diagnosed with clear cell renal cell carcinoma (RCC). A 56 year old female presented with dysphagia and was found to have a left thyroid nodule and left superior cervical LN with suspicious sonographic features. Fine needle aspiration biopsy (FNAB) demonstrated PTC in the left thyroid nodule and MTC in the left cervical LN. Histopathology demonstrated multifocal PTC with 3/21 LNs positive for metastatic PTC. One LN in the left lateral neck dissection exhibited features of both MTC and PTC within the same node. In the right lobe, a 0.3 cm focus of MTC with extra-thyroidal extension was noted. Given persistent calcitonin elevation, a follow-up ultrasound displayed an abnormal left level 4 LN. FNAB showed features of both PTC and MTC on the cytopathology itself. The patient underwent repeat central and left radical neck dissection with 3/6 LNs positive for PTC in the central neck and 2/6 LNs positive for intermixed PTC and MTC in the left neck. There was no evidence of distant metastases on computed tomography and whole body scintigraphy, however a 1.9 x 2.5 cm enhancing mass within the right inter-polar kidney was discovered. This lesion was highly suspicious for RCC. Surgical pathology revealed a 2.5 cm clear cell RCC, Fuhrman grade 2/4, with negative surgical margins. She continues to be observed with stable imaging of her triple malignancies.Learning points:Mixed medullary-papillary thyroid neoplasm is characterized by the presence of morphological and immunohistochemical features of both medullary and papillary thyroid cancers within the same lesion. Simultaneous occurrence of these carcinomas has been previously reported, but a mixed disease within the same lymph node is an infrequent phenomenon.Prognosis of mixed medullary-papillary thyroid carcinomas is determined by the medullary component. Therefore, when PTC and MTC occur concurrently, the priority should be given to the management of MTC, which involves total thyroidectomy and central lymph node dissection.Patients with thyroid cancer, predominantly PTC, have shown higher than expected rates of RCC. To our knowledge, this is the first report describing the combination of MTC, PTC, and RCC in a single patient.

SIN1, a critical component of the mTOR-Rictor complex, is overexpressed and associated with AKT activation in medullary and aggressive papillary thyroid carcinomas

Molecular Rearrangements and Morphology in Thyroid Cancer

Occult Medullary Carcinoma of the Thyroid Presenting as Neck and Parapharyngeal Metastases

The prognosis of the follicular variant of papillary thyroid carcinoma (FVPTC) falls between that of classical papillary thyroid carcinoma (cPTC) and follicular thyroid carcinoma (FTC) (1). FVPTC has lower mortality and less frequent distant metastases than FTC, but higher mortality and more frequent distant metastases than cPTC. FVPTC has fewer lymph node metastases and less frequent infiltrative disease and extrathyroidal extension than cPTC, but more than FTC. But is it a hybrid disease or a mixture of diseases? The pathological appearance of a follicular-patterned tumor with the nuclear features of cPTC suggests that FVPTC is a hybrid. However, the heterogeneous nature of the disease and the mutational profile of FVPTC strongly suggest that it is a mixture of diseases (2). It is the intersection of classical descriptive pathology and modern molecular biology that permits an understanding of this group of diseases.

ObjectiveThe co-existence of medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) is rare. The study analyzed the clinicopathological findings and prognosis of concomitant PTC in MTC patients.MethodsClinicopathological data and follow-up outcomes of 25 patients with concurrent medullary and papillary thyroid carcinoma (combination group) between January 2009 and May 2024 were collected and analyzed retrospectively. We compared clinicopathologic characteristics and follow-up outcomes between patients with concurrent MTC and PTC (combination group) and those with MTC alone (MTC group).ResultsThe 25 patients with concurrent MTC and PTC comprised 19 females and 6 males. There were no statistically significant differences between the combination group and the MTC group in terms of age, gender, or pathological features such as the diameter of MTC lesions, multifocality, extra-thyroidal extension (ETE), number of lymph node (LN) resected, the number of LN metastasis, the maximum diameter of LN metastasis, and TNM staging. The recurrence rate was similar between the two groups. Univariate analysis showed that the max tumor diameter, capsule invasion, extracapsular invasion and recurrent nerve invasion were associated with the risk of biochemical/structural abnormalities in MTC group. Multivariate analysis showed that only the max tumor diameter and capsule invasion were significant independent prognostic factors for biochemical/structural abnormalities.ConclusionThe result of this comparative study between patients with MTC and PTC co-existence and those with MTC alone showed similar invasiveness and prognosis.