Diffuse sclerosing variant of papillary thyroid carcinoma: outcomes of 33 cases

Introduction: Diffuse sclerosing variant of PTC (DSV-PTC) is an uncommon subtype of thyroid cancer. Although an aggressive behavior is often recognized, prognostic significance is still under debate. Objectives: To describe the clinicopathological features and outcomes of a series of DSV-PTC patients. Methods: Retrospective data collection regarding 33 patients diagnosed with DSV-PTC followed at the Endocrine Department of the Portuguese Institute of Oncology in Lisbon between 1981 and 2020. Results: 26 patients (78.8%) were females with a mean age at presentation of 29.4±11.7 years-old. Mean time of follow-up was 19.5±10.6 years (range 0.5 to 39). Histologically, bilateral tumors were present in 72.7% patients (n=24), thyroid capsular invasion was documented in 57.6% (n=19), 45.4% (n=15) had extrathyroidal extension (ETE), and 42.4% (n=14) had lymphovascular invasion. Most patients were staged pT3 (42.4%, n=14) and pN1 (81.8%, n=27). Median lymph nodes resected were 16. None of the patients showed distant metastases at presentation. All patients were treated at least once with 131I. During follow-up, 4 patients (14.8%), with persistent neck disease, were diagnosed with distant metastases, all of them in the lung. Two patients (1.8%) presented recurrent disease in the neck after being considered with no evidence of disease. At the last appointment, 18 patients (54.5%) were in remission, 4 (12.1%) had biochemical evidence of disease, 6 had structural disease, and for 5 patients disease status was considered as undetermined. There was no disease related mortality. Discussion/Conclusion: Our study confirms that DSV-PTC is diagnosed more often in young patients and exhibits a local extensive disease at presentation. On the other hand, even in the presence of distant metastases, no patient died during follow-up.

Comparison of the clinical characteristics of primary thyroid lymphoma and diffuse sclerosing variant of papillary thyroid carcinoma

Objective: Both primary thyroid lymphoma (PTL) and diffuse sclerosing variant of papillary thyroid carcinoma (DSVPTC) are two rare malignant tumours with different therapies and prognoses. This study compared their clinical features. Methods: From a retrospective review of the pathologic database at our institute between January 2015 and August 2020, 52 PTL patients and 40 DSVPTC patients were included. Demographic, clinical, laboratory and ultrasound data were extracted from electronic medical records. Statistical analyses were performed using GraphPad Prism 5.0. Results: Both PTL and DSVPTC were more likely to occur in women (83.7% and 67.5%), but DSVPTC patients were younger (median age: 36 vs 64.5), had fewer compressive symptoms, and more frequently had neck lymph node metastasis than PTL patients. The prevalence of Hashimoto’s thyroiditis (HT) and hypothyroidism was significantly higher in PTL patients than in DSVPTC patients (31% vs 17.5%). Hyperthyroidism could only be found in DSVPTC patients, which accounted for 7.5%. Heterogeneous echogenicity and irregular edges were frequently observed in both PTL and DSVPTC. However, compared with PTL, DSVPTC exhibited smaller lesion sizes, higher frequencies of diffuse sonographic patterns and calcification, and lower frequencies of hypoechoic features and internal blood flow signal. The overall survival rate with PTL was 77.23%, which was lower than that with DSVPTC (90.91%), but this difference was not significant (p=0.096). Conclusion: Clinical characteristics such as age, compression symptoms, and sonographic features such as a large mass with heterogeneous echogenicity, hypoechoic, irregular edges, and calcification are helpful for impression diagnosis of PTL and DSVPTC before surgery.

Incidental Diffuse Sclerosing Variant Papillary Thyroid Cancer in Grave’s Disease

The diffuse sclerosing variant papillary thyroid carcinoma (DSPTC) is an uncommon form of this neoplasm. Some studies describe its high propensity for tumor invasion, metastasis, and mortality compared with classic papillary thyroid carcinoma. Histologic features of DSPTC may resemble diffuse inflammation as seen with Grave’s or Hashimoto’s thyroiditis, which makes initial diagnosis challenging. A 27-year-old female with Noonan’s Syndrome was evaluated on an outpatient basis after developing atrial fibrillation de novo. Thyroid function tests were consistent with hyperthyroidism with TSH: <0.005 (n: 0.300-3.000 uIU/mL), FT4: 3.59 (0.71-1.85 ng/mL) and FT3: 16.77 (n: 2.0-7.0 pmol/L). Diffuse goiter was noted on physical exam, but no ophthalmopathy or dermopathy was present. TRAB and TSI were elevated at 38.4 (n: <16%) and 423% (n: <140%) respectively. A twenty-four-hour radioiodine uptake was 48% (n:10-35%) and described as essentially homogenous with two foci of decreased radiotracer concentration suggestive of cold nodules. Thyroid ultrasound showed diffuse nodularity bilaterally with associated clusters of calcifications and no discrete nodules. No abnormal appearing lymph nodes were identified. Fine-needle aspiration of both nodular areas was positive for DSPTC. Total thyroidectomy with central neck dissection was performed. Gross and microscopic post-surgical pathology confirmed the presence of diffuse sclerosing papillary thyroid cancer, along with local metastasis to one central lymph node. Patient was scheduled for radioactive iodine therapy. Diffuse sclerosing variant is considered an aggressive histotype of papillary thyroid cancer. Ultrasound features include diffuse scattered microcalcifications with or without discrete nodules that may be confused with chronic inflammatory changes. Despite the limited number of cases, DSPTC is recognized to have specific characteristics, a high female to male ratio, and a young patient age. DSPTC has a high potential for aggressive biologic behavior if not treated promptly at the time of diagnosis. When suspected, total thyroidectomy with lymph node excision followed by radioiodine therapy has been proposed as the correct management to decrease the risk of persistent or recurrent disease.

A Case of Diffuse Sclerosing Variant of Papillary Thyroid Cancer: An Aggressive Variant Presenting With Recurrent Locoregional Nodal Disease

Diffuse sclerosing variant (DSV), a subtype of papillary thyroid carcinoma (PTC), has been considered more aggressive than classical PTC given that it usually presents with extrathyroidal invasion and lymph node metastasis at the time of diagnosis. Data about the risk of recurrence and prognosis is still debatable. Hence, we report a 29-year old woman with recurrent DSV-PTC that presented with pulmonary metastasis after multiple surgical interventions, radioactive iodine (RAI) therapy and a negative whole-body scan (WBS) ten months prior to this finding. A 29-year old woman without history of systemic illness, family history of thyroid cancer or neck radiation exposure, developed diffuse goiter at age 23. A thyroid and neck ultrasound revealed an enlarged heterogeneous thyroid gland with innumerable small bright echogenicities scattered throughout and bilateral neck adenopathy. No thyroid nodules were seen. Anti-thyroglobulin antibodies (anti-Tg Ab) were positive. A fine needle aspiration biopsy (FNAB) was positive for PTC with cytologic features suggestive of DSV. Subsequently, total thyroidectomy was performed, and 15 lymph nodes were positive for PTC. Thyroid suppression therapy was started maintaining goal of TSH <0.1ng/dL. Patient had a second neck dissection one month later, where 7 lymph nodes were positive for PTC. Pathology revealed chronic lymphocytic thyroiditis with bilateral multifocal PTC and staging pT3N1b. Two months after thyroidectomy, RAI therapy was provided with 153.6mCi of I-131. Post RAI therapy WBS and SPECT/CT demonstrated persistent metastasis to lymph nodes. After this finding, a third left neck dissection was done with additional lymph nodes resection positive for PTC. A second RAI therapy with 138mCi of I-131 was administered the following year. Continued surveillance suggested recurrence of PTC due to new suspicious nodules on neck along with increased anti-Tg Ab level from 44.64 to 95 IU/mL. FNAB confirmed PTC of five different locations of the thyroid bed. She had two additional neck dissections. Metastasis of lymph nodes was confirmed at multiple levels in the right neck and central compartment. Ten months after being without evidence of PTC recurrence in previous WBS and FDG-PET/CT, she started to develop hemoptysis. A neck and chest CT scan demonstrated innumerable bilateral hyperdensities consistent with pulmonary metastasis. At this time, TSH continued suppressed in 0.06 mIU/mL but, anti-Tg Ab had increased to 160 IU/mL. DSV-PTC has been shown to be at an advanced stage upon diagnosis. Furthermore, it has been documented that distant metastasis could also be present at this time with pulmonary metastasis being the most common. Nonetheless, some authors suggest that the advanced presentation could be due to delayed diagnosis rather than DSV intrinsic behavior. Besides its aggressive nature, DSV-PTC risk of recurrence remains controversial.

Diffuse Sclerosing Variant of Papillary Thyroid Carcinoma Presenting as Suspected Cervical Osseous Metastasis : A Case Report and Literature Review

Background : The diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) is an uncommon variant of PTC. Although its histologic features are aggressive, its prognostic significance remains controversial. Case summary : Bone scan of 41-year-old woman with a history of breast and thyroid cancers showed suspected cervical osseous metastasis during the previous cancer follow-up. Further, magnetic resonance imaging was recommended. Preoperative fine needle aspiration cytology showed features of thyroid papillary carcinoma and postoperatively, the mass was diagnosed to DSV-PTC showing features of numerous and diffuse calcification and squamous metaplasia. Conclusion : Herein, we describe the pathologic features, including histologic and fine-needle aspiration cytologic features, and prognostic implications through a literature review.

MON-533 Diffuse Sclerosing Variant Papillary Thyroid Cancer: Clinical and Histopathological Features, Mutational Profile, Management and Outcome

Diffuse sclerosing variant (DSV) is a rare subtype of papillary thyroid cancer (PTC). Whether it represents a higher grade subtype than conventional PTC is not quite clear. Furthermore, there are limited data on its long-term outcome and its molecular genetics. In this report, we studied all cases of DSV PTC seen at our center during the last 20 years. Out of more than 6000 patients (pts) with differentiated thyroid cancer, only 37 were DSV. We reviewed the clinical and histopathological features, management and outcome of these cases. In addition, molecular genetics is partially achieved; 17 out of these 37 cases have been genotyped for BRAFV600E, TERT promotor mutations, NRAS, HRAS and KRAS mutations. The molecular profiling of the other 20 cases is being done. A total of 37 pts were studied {(12 Males:25 Females, median age 21 years (8-89)}. One pt had lobectomy and the other 36 pts (97.3%) had a total thyroidectomy. Central only (4 pts) or central/lateral lymph node dissection (29 pts) were performed. The median tumor size was 4.5 cm (1.5-8.1). The tumor was multifocal in 27 cases (73%), with extrathyroidal invasion in 27 (73%) and lymphovascular invasion in 24 pts (64.8%). A background lymphocytic thyroiditis was present in 12 pts (32.4%). Lymph node metastases were present in 34 pts (92%) and distant metastases in 13 pts (35%). The sites of metastasis are lungs in 12 pts (32.4%) and lungs and bone in 1 pt. Twenty pts (54.1%) were in TNM8 stage 1, 10 pts (27%) in stage 2, 1 (2.7%) in stage 4a, 3 (8.1%) in stage 4b and 3 unstageable. The ATA risk classification for these pts was 4 pts (10.8%) in low, 12 (32.4%) in intermediate, 19 (51.4%) in high-risk groups and 2 could not be assessed. I-131 was administered to 33 pts (89.2%). The median administered activity was 136 mCi (46-218). Fifteen pts (40.5%) received additional therapies (3 surgeries, 7 RAI, 5 surgeries, and RAI). In 17 pts (46%) which were genotyped, only 3 tumors (8.1%) had BRAFV600E mutation, 1 (2.7%) had TERT promotor C228T mutation and none had RAS mutations. At the last follow up, 15 pts (40.5%) achieved an excellent response, 9 (24%) an indeterminate response, 6 (16.2%) with a structural disease, and 7 (19%) were lost for follow up. Conclusion: DSV PTC is a rare variant, occurs mostly in adolescent and young pts, characterized by aggressive histopathological features and high rates of lymph node and distant metastases but the commonly reported mutations in PTC are rare in DSV and mortality is absent.