OBJECTIVES

To report a case of triple primary malignant neoplasms in a 70-year-old woman diagnosed with follicular and papillary thyroid carcinoma and diffuse B-cell lymphoma of the right submandibular gland and cervical lymph nodes.

METHODS

Design:Case Report

Setting:Tertiary Government Training Hospital

Patient: One

RESULTS

A 70- year-old woman presented with a four-year history of gradually enlarging anterior neck mass, associated with a right submandibular mass and neck nodes for one year. The gradual progression of her symptoms made the patient think that it was a benign condition. This led to a delay in medical consultation. The patient underwent total thyroidectomy with functional neck dissection of the ipsilateral right neck. Histopathology revealed simultaneous follicular and papillary thyroid carcinoma, and diffuse B-cell lymphoma of the cervical lymph nodes. The patient was referred to medical oncology and nuclear medicine for further management.

CONCLUSION

Our patient was incidentally diagnosed with follicular and papillary thyroid carcinoma and diffuse B cell lymphoma of the cervical lymph nodes after surgery. Such triple primary malignant neoplasms in a single individual are rare, and as in our case, may only be diagnosed in hindsight.

Human ; Female ; Aged: 65-79 Yrs Old ; Carcinoma ; B-lymphocytes ; Adenocarcinoma, Follicular ; Neoplasms ; Submandibular Gland ; Lymph Nodes ; Lymphoma, B-cell ; Thyroid Gland ; Thyroid Cancer, Papillary ; Thyroidectomy

We report a case of an uncommonly aggressive presentation of the rare entity of synchronous papillary (PTC) and follicular thyroid carcinomas (FTC) in a 67-year-old woman initially presenting with thyrotoxicosis from Graves’ disease. She was found to have two thyroid nodules with extensive intra-cardiac tumour thrombus, symptomatic left pelvis bony metastasis with pathological fracture, pulmonary metastases and mediastinal lymph node metastases. Further investigations suggested a diagnosis of synchronous papillary and metastatic follicular thyroid cancer. Treatment with radical surgery followed by adjuvant therapeutic radioiodine ablation was proposed, but the patient declined all forms of cancer-specific therapy and was elected solely for a palliative approach to treatment. We discuss the diagnostic considerations in arriving at the diagnosis of synchronous thyroid malignancy – in this case the clear features of PTC and the strong probability of FTC due to invasiveness and metastatic follicular lesions. This case underscores potential limitations of the ACR TI-RADS system, notably with certain ultrasonographic features suggesting malignancy that might not be adequately captured. Notably, the aggressive presentation of DTC in this case may be contributed by the concurrent presence of Graves’ Disease, suggesting heightened vigilance when assessing potential thyroid malignancies in such patients.
Papillary Thyroid Carcinoma ; Thyroid Cancer, Papillary ; Follicular Thyroid Carcinoma ; Adenocarcinoma, Follicular ; Graves Disease

Humans ; Thyroid Neoplasms/pathology* ; Carcinoma, Papillary/pathology* ; World Health Organization ; Adenocarcinoma, Follicular/pathology*

A 23-year-old woman underwent left thyroid lobectomy and isthmusectomy for a 2 cm diameter firm mass on the left side of the neck that was also visualized on ultrasonography. The specimen consisted of a 22-gram thyroid gland composed of the left lobe, isthmus and a pyramidal lobe. Cut section of the left lobe showed a 3.5 cm diameter solitary, discrete and encapsulated mass with a tan lobulated and solid cut surface. The rest of the thyroid tissues had red-brown meaty cut surfaces. Microscopic section shows a follicular-patterned proliferation enclosed by a thin fibrous capsule with frequent Sanderson polster-like papillary excrescences. (Figures 1 and 2) Both the follicular and the papillary structures are lined by cuboidal to columnar follicular epithelial cells that had ample eosinophilic to pale cytoplasm and uniformly sized, minimally enlarged, generally round, and monolayered nuclei without nuclear grooving, folds, pseudoinclusions, and chromatin clearing. There are no mitotic figures seen. Some of the papillary structures have delicate vascular cores. (Figure 3) There are no psammoma bodies noted. The follicles contain variable amounts of pale eosinophilic colloid ranging from colloid-poor crowded follicles to those with ample colloid that have frequent peripheral scalloping. (Figure 4) Exhaustive sections failed to disclose capsular or vascular invasion. Based on the microscopic features, a diagnosis of follicular adenoma with papillary architecture was rendered.
Follicular thyroid carcinoma ; papillary thyroid carcinoma

Background: The majority of thyroid malignancies are differentiated thyroid carcinomas (DTCs). We examined the incidence, disease extent, recurrence and disease-specific mortality (DSM) of DTC among Filipinos residing in the Philippines and Filipino immigrants. Methodology: In accordance with the 2020 PRISMA statement, we performed a systematic literature search in MEDLINE, Google Scholar, EBSCO, Cochrane and Clinicaltrials.gov for the period January 1, 1980 until January 27, 2022. Pooled incidence rate ratio and pooled proportions of disease extent, recurrence and DSM were determined. Results: Literature search yielded 1,852 studies. Out of 26 articles retrieved, nine retrospective case controls and cohorts were included. Incidence of DTC was significantly higher in female Filipino immigrants compared with non-Hispanic whites (NHW). Distant metastases and recurrence were more common among Filipinos and Filipino immigrants compared with NHW. Limited data showed higher DSM in Filipino immigrants and NHW than Filipinos, which may be influenced by reporting bias. Conclusion This review supports the trend of increased incidence and recurrence of DTC among Filipinos, although case registries are essential to confirm these findings. In the setting of the newly released Philippine guidelines for DTC, prospective studies with active long-term follow-up will help detect any changes in the outcomes of DTC among Filipinos.
Filipino ; papillary thyroid carcinoma ; follicular thyroid carcinoma

Adenocarcinoma, Follicular/surgery* ; Carcinoma, Squamous Cell ; Humans ; Thyroid Neoplasms/surgery*

We describe herein histologic, immunohistochemical, and molecular findings and clinical manifestations of a rare case of an extremely well differentiated papillary thyroid carcinoma (EWD-PTC). Similarly, it is also difficult to diagnose follicular variant papillary thyroid carcinoma (FVPTC), whose diagnosis is still met with controversy. A recently reported entity of well-differentiated tumor of uncertain malignant potential (WDT-UMP) is added to the diagnostic spectrum harboring EWD-PTC and FVPTC. We report this case, because EWD-PTC is different from FVPTC in its papillary architecture, and also from WDT-UMP in its recurrence and metastatic pattern. These morphologically deceptive entities harbored diagnostic difficulties in the past because the diagnosis depended solely on histology. However, they are now diagnosed with more certainty by virtue of immunohistochemical and molecular studies. We experienced a case of EWD-PTC, which had been diagnosed as adenomatous hyperplasia 20 years ago and manifested recurrence with lymph node (LN) metastasis 7 years later. After another 7 years of follow-up, a new thyroid lesion had developed, diagnosed as FVPTC, with LN metastasis of EWD-PTC. One year later, the patient developed metastatic FVPTC in the skull. Immunohistochemically, the EWD-PTC was focally positive for CK19, negative for galectin-3, and focally negative for CD56. Molecular studies revealed BRAF-positivity and K-RAS negativity. The FVPTC in the left thyroid showed both BRAF and K-RAS negativity. In conclusion, EWD-PTC and FVPTC share similar histologic features, but they are different tumors with different molecular biologic and clinical manifestations. A large cohort of EWD-PTC should be included in further study.
Adenocarcinoma, Follicular/pathology/secondary ; Adult ; Carcinoma, Papillary, Follicular/pathology/*secondary ; Female ; Galectin 3/analysis ; Humans ; Hyperplasia/pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Recurrence, Local/pathology ; Skull Neoplasms/*secondary ; Thyroid Neoplasms/*pathology

Follicular variant papillary thyroid cancer (FVPTC) is the second most common subtype after conventional PTC. We compared ultrasonographic (US) features of FVPTC to those of conventional PTC according to tumor size. We reviewed US findings, pathologic reports, and medical charts of 249 PTC patients with surgically proven disease (83 FVPTCs, 166 conventional PTCs) at our institution from January 2007 to December 2012. FVPTCs were divided into PTC-like and follicular neoplasm (FN)-like based on sonographic characteristics. PTC-like features were defined as having at least one malignant feature (taller-than-wide shape, infiltrative margin, marked hypoechogenicity, and micro-calcifications), whereas FN-like cancers showed oval solid features without malignant features. FVPTCs showed a higher rate of FN-like features than conventional PTCs. Of 166 conventional PTCs, 13 (7.8%) had FN-like features and 153 (92.2%) had PTC-like features, whereas of the 83 FVPTCs, 31 (37.3%) had FN-like features and 52 (62.7%) had PTC-like features. Macro-FVPTCs showed a higher rate of FN-like features than micro-FVPTCs (P < 0.001). Of 21 macro-FVPTCs, 18 (85.7%) had FN-like features and 3 (14.3%) had PTC-like features, whereas of the 62 micro-FVPTCs, 13 (21%) had FN-like features and 49 (79%) had PTC-like features. There were no differences in multifocality, extrathyroidal invasion, and lymph node metastasis between PTC-like FVPTCs and FN-like FVPTCs. FVPTCs showed fewer sonographic malignant features than conventional PTCs. In particular, FVPTCs larger than 1 cm had a more frequent benign sonographic appearance. Therefore, if fine-needle aspiration result is suspicious for PTC in a nodule larger than 1 cm with no suspicious US features, the possibility of FVPTC might be considered.
Adult ; Carcinoma, Papillary, Follicular/*diagnostic imaging/pathology ; Demography ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Thyroid Neoplasms/*diagnostic imaging/pathology ; *Ultrasonography

PURPOSE: The goal of this study was to validate the ultrasonography (US) and cytopathological features that are used in the diagnosis of the follicular variant of papillary thyroid carcinoma (FVPTC) and to characterize the role of BRAF(V600E) mutation analysis in the diagnosis of FVPTC. METHODS: From May 2012 to February 2014, 40 thyroid nodules from 40 patients (mean age, 56.2 years; range, 26 to 81 years) diagnosed with FVPTC were included in this study. The US features of the nodules were analyzed and the nodules were classified as probably benign or suspicious for malignancy. Twenty-three thyroid nodules (57.5%) underwent BRAF(V600E) mutation analysis. Clinical information and histopathologic results were obtained by reviewing the medical records of the patients. RESULTS: Thirty nodules (75.0%) were classified as suspicious for malignancy, while 10 (25.0%) were classified as probably benign. Seven of the eight nodules (87.5%) with atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) cytology showed suspicious US features, while one of the two nodules (50.0%) with follicular neoplasm cytology presented suspicious US features. Five of the 23 nodules (21.7%) that underwent BRAF(V600E) mutation analysis had positive results, all of which were diagnosed as suspicious for malignancy or malignant based on cytology. None of the nodules with benign, AUS/FLUS, or follicular neoplasm cytology were positive for the BRAF(V600E) mutation. CONCLUSION: US features allow nodules to be classified as suspicious for malignancy, and the presence of suspicious US features in nodules with ambiguous cytology may aid in the diagnosis of FVPTC. BRAF(V600E) mutation analysis is of limited value in the diagnosis of FVPTC.
Biopsy, Fine-Needle ; Carcinoma, Papillary ; Carcinoma, Papillary, Follicular ; Diagnosis ; Humans ; Medical Records ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroid Nodule ; Ultrasonography*

We report a rare case of co-occurrence of papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC) and primary thyroid lymphoma. A 55-year-old woman presented with a large mass in left lobe of thyroid, biopsy confirmed diffuse large B-cell lymphoma. After 4 cycles of rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisolone chemotherapy, positron emission tomography scan revealed markedly decreased in size, but still present. Repeated ultrasonography-guided gun biopsies of 2 lesions indicated Hurthle cell neoplasm. After total thyroidectomy and bilateral central lymph node dissection, residual hypermetabolic lesion of left lobe was determined to be FTC and right lower lesion to be nodular hyperplasia. Besides, a PTC was incidentally detected in left lobe. If there are multiple nodular lesions at diagnosis or there is insufficient response after 1st line chemotherapy for primary thyroid lymphoma, each lesion should be biopsied to confirm its pathological type.
Adenocarcinoma, Follicular ; Biopsy ; Carcinoma, Papillary* ; Cyclophosphamide ; Diagnosis ; Doxorubicin ; Drug Therapy ; Female ; Humans ; Hyperplasia ; Lymph Node Excision ; Lymphoma* ; Lymphoma, B-Cell ; Middle Aged ; Positron-Emission Tomography ; Prednisolone ; Rituximab ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy ; Vincristine