Despite the relatively high prevalence of thyroid cancer, the occurrence of multiple synchronous, distinct subtypes of primary thyroid carcinoma is uncommon. The incidental finding of papillary thyroid microcarcinoma in a gland with a biologically relevant follicular or medullary carcinoma is more frequent than the synchronous occurrence of multiple clinically significant carcinomas. We report a case of synchronous papillary and follicular thyroid carcinomas metastatic to lymph node and bone, respectively. Next generation sequencing showed BRAF V600E mutation in the primary papillary carcinoma and NRAS Q61R mutation in the primary follicular carcinoma and bony metastasis. To our knowledge, this is the first reported case of synchronous and metastatic primary papillary and follicular carcinomas, and the first report of synchronous BRAF V600E mutated papillary and NRAS mutated follicular carcinoma.
This study highlights the importance of routine histopathologic evaluation of embolectomy specimens in patients with and without documented neoplasia.
Creating visual art to teach and learn histologic concepts is uncommon. A pilot visual art program was developed for use in first-year medical student courses that include histology with the hypothesis that creating visual art would subjectively improve the learning process and lead to learner-based personal incorporation of art into in future learning. Prior to the term, volunteers (n=25) were recruited from 89 first-year medical students. The volunteer group was given art supplies and encouraged to draw histologic images in a free-form setting without restrictions. The control group (n=64) consisted of non-volunteers. Pre- and post-term surveys were distributed to all students, of which 72% and 45% completed the surveys, respectively. Regardless of participation, a majority of students viewed art as a valuable tool to learn medicine prior to and following the term (73% and 82.5%, respectively), however less than half admitted to using art to learn medical concepts (42% and 40%, respectively). In the post-term survey, a higher percentage of students in the experimental group stated they will use art to learn medical concepts in the future (75% vs 40.6%). Most students considered art to be a valuable resource to learn concepts in medicine, including all the students who participated in the art program. Based on the number of students who reported intent to change behavior, the initial hypothesis is supported. Many students favor incorporation of visual art into medical education, we believe that creating visual art may be a worthwhile adjunct tool for histology education.
Papillary thyroid carcinoma (PTC) is defined by an invasive growth pattern and classic nuclear features: enlarged, grooved, overlapping nuclei with chromatin clearing and intranuclear cytoplasmic pseudoinclusions (INCP). True INCPs are characteristic of PTC, but may infrequently be seen in noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP). Nuclear abnormalities that mimic INCP ("pseudo-pseudoinclusions") are common in a variety of thyroid lesions. H&E and ubiquitin-stained whole tissue sections of classic PTC (n = 25) and NIFTP (n = 35) were evaluated. On H&E, true INCPs were present in all (100%) PTCs and absent in all NIFTPs (0%). Pseudo-pseudoinclusions were present in 13 (37%) NIFTPs. In 24 (96%) PTCs, ubiquitin was strongly expressed within INCPs. In NIFTPs, optically clear nuclei or pseudo-pseudoinclusions did not express ubiquitin (0/35). Occasionally, nuclear vacuoles in NIFTP demonstrated a marginated staining pattern, in which strong ubiquitin expression was seen at the periphery of the nucleus, but the central pale area was negative. In addition, 2 NIFTPs demonstrated intrafollicular psammomatoid calcifications which were strongly ubiquitin-positive. Psammoma bodies in PTC were ubiquitin-negative in the majority of cases. We report a previously undescribed finding: strong ubiquitin expression in true INCPs in PTC, absence of true INCPs in NIFTP, and absence of ubiquitin expression in pseudo-pseudoinclusions in NIFTP. This finding supports the difference between true INCPs (found only in PTC) and pseudo-pseudoinclusions (found in NIFTP). Using strict histologic criteria and ubiquitin immunostaining, the presence of true pseudoinclusions may exclude a diagnosis of NIFTP. Caution should be exercised when interpreting nuclear vacuoles or pseudo-pseudoinclusions.
Metastatic follicular thyroid carcinoma (FTC) is rare. The aim of this study was to determine the clinical, histologic, and molecular differences between patients with metastatic FTC who present with distant metastatic (DM) disease versus those who present with a primary thyroid nodule (PT). Clinical and pathologic information was extracted from the medical record and surgical pathology report. When available, slides were reviewed. Molecular testing was performed on available primary and/or metastatic lesions. Thirty-six patients with metastatic FTC were identified: 15 DM and 21 PT. DM patients were significantly older than those with PT (P=0.0001). In DM patients, bone was the most common site of initial metastasis (P=0.03), compared with lung in PT patients (P=0.03). Unique to primary carcinomas in DM patients was extensive intratumoral fibrosis (50%), occasionally reaching such a degree as to obscure histologic features of malignancy (2 cases). Oncocytic features were more common in those who presented with PT (P=0.03). Pathogenic mutations were identified in 85% of cases, most commonly in RAS (55%) and TERT promoter (45%); of these, combined RAS and TERT was present in 30%. Pathogenic PTEN, NF1, RET, and BRCA2 mutations were also identified. The prevalence and type of pathogenic mutations did not differ between DM and PT patients. The acquisition of a pathogenic mutation in the metastatic focus that was not present in the primary carcinoma was rare (1 case). In summary, FTC presenting with DM compared with PT was more likely to be present in an older age group, to metastasize to bone, and to demonstrate extensive fibrosis possibly representing histologic regression.
In follicular thyroid neoplasms without invasion, a diagnosis of atypical adenoma (AA) (follicular tumor of uncertain malignant potential) may be rendered if atypical features (indefinite capsular/vascular invasion, necrosis, solid growth, increased mitoses) are present. This study compares clinical, histologic, and molecular features of patients with AAs (n=31), nonmetastatic follicular thyroid carcinoma (nmFTC) (n=18), and metastatic follicular thyroid carcinoma (mFTC) (n=38). Patients with mFTC were older. Mitotic activity in areas of solid growth was greatest in mFTC (P=0.05). Oncocytic tumors tended to show solid growth (P=0.04). The presence or frequency of capsular and/or vascular invasion was not different between nmFTC and mFTC. TERT promoter mutations were higher in patients with mFTC (50%) than nmFTC (25%) and AA (10%) (P=0.02). TERT promoter mutation was associated with necrosis (P=0.01) and solid growth plus increased mitoses (P=0.03). Necrosis and TERT promoter mutations were identified in all groups, most frequently in mFTC. The combination of solid growth with increased mitoses, necrosis, and TERT promoter mutation was only seen in follicular carcinomas. Poorly differentiated features, vascular invasion, and TERT promoter mutation correlated with metastasis in FTC. Given the low frequency of necrosis and TERT promoter mutation in AAs, close clinical follow-up is recommended in patients with these findings, especially if additional atypical features (such as solid growth plus mitoses) are present.
Sinus histiocytosis with massive lymphadenopathy, or Rosai-Dorfman disease, is a rare, benign type of non-Langerhans cell histiocytosis. The radiological findings are often nonspecific, potentially mimicking malignancies. The diagnosis is ultimately made based on pathology, in which the lymph nodes are characterized by a dilated subcapsular sinus filled with histiocytes that can exhibit emperipolesis. Immunohistochemically, the histiocytes are variably CD68 positive and reliably negative for CD1a. The features of head and neck sinus histiocytosis with massive lymphadenopathy are exemplified in this radiology-pathology correlation sine qua non article.
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