The hobnail variant of papillary thyroid carcinoma (HVPTC) represents a distinctive and relatively rare histological subtype of thyroid malignancies. This variant is characterized by its unique cellular morphology with a hobnail appearance, that is, cells with apically positioned nuclei. There are other characteristics like micropapillary pattern and loss of cohesiveness of cells, which are indicative of HVPTC. It can be difficult to distinguish this pattern from other thyroid neoplasms; thus, a thorough microscopical examination is required. Thyroglobulin, thyroid transcription factor-1 (TTF-1), and other thyroid markers are commonly expressed by the tumor cells. Clinically, HVPTC is similar to conventional papillary thyroid cancer (PTC) in many aspects like incidence and epidemiology, but the former is associated with a worse prognosis. According to some research, the hobnail variety might behave more aggressively than conventional PTC, which highlights how crucial it is to identify and comprehend this distinct subtype. While the genetic and molecular underpinnings of HVPTC are still being elucidated, some studies have reported associations with specific genetic alterations, including BRAF, TP53, and TERT mutations. Investigating these molecular signatures may contribute to a better understanding of the variant\'s pathogenesis and potentially guide targeted therapeutic approaches in the future. In order to customize treatment plans, histopathology is essential in correctly diagnosing it. In this article, we present a case of PTC which presented as a solitary nodule on ultrasonogram in a 40-year-old female.

Although papillary thyroid carcinoma (PTC) is considered to have an excellent prognosis, some recently identified more aggressive variants show reduced overall survival rates. Hobnail PTC (HPTC) was newly recognized as one of these aggressive forms, affecting recurrence, metastasis, and overall survival rates. Herein, we performed a systematic review and meta-analysis of studies including cases or case series with patients with HPTC. Furthermore, we included our individual case series consisting of six patients. The pooled mortality rate in the cohort, consisting of 290 patients, was 3.57 (95% CI 1.67−7.65) per 100 person/years. No sex differences could be observed concerning mortality (p = 0.62), but older age and tumor size significantly affected mortality (p = 0.004 and p = 0.02, respectively). The percentage of hobnail cells did not affect mortality (p = 0.97), neither did the presence of BRAF mutations. Classical characteristics such as the presence of extrathyroidal extension (p = 0.001), distant metastases (p < 0.001), and lymph node metastases (p < 0.001) all had a significant impact on mortality. Thus, HPTC appears to correlate with worse overall survival, and all PTC cases should be carefully assessed for this variant.

Papillary thyroid carcinoma (PTC) is a miscellaneous disease with a variety of histological variants, each with its own mutational profile, and clinical and prognostic characteristics. Identification of microRNA (miRNA) expression profiles represents an important benchmark for understanding the molecular mechanisms underlying the biological behavior of these unique PTC subtypes in order that they be better characterized. We considered a series of 35 PTC samples with a histological diagnosis of either hobnail (17 cases) or classical variant (nine cases) and with a specific BRAF p.K601E mutation (nine cases). We determined the overall miRNA expression profile with NanoString technology, and both quantitative reverse transcription-PCR and in situ hybridization were used to confirm selected miRNAs. The miRNA signature was found to consistently differentiate specific histotypes and mutational profiles. In contrast to the BRAF p.K601E mutation and classic PTCs, three miRNAs (miR-21-5p, miR-146b-5p, and miR-205-5p) were substantially overexpressed in the hobnail variant. The current study found that different miRNA signature profiles were linked to unique histological variants and BRAF mutations in PTC. Further studies focusing on the downstream pathogenetic functions of mRNAs in thyroid neoplasms are warranted.

Hobnail variant of papillary thyroid carcinoma (HV-PTC) is an unusual entity recently included in WHO classification of endocrine tumors (2017) and proposed as an aggressive variant of PTC. Compared to patients of classical counterparts, HV-PTC frequently has extrathyroidal extension, exhibits nodal or distant metastasis, and responds poorly to radioiodine treatment, leading to increased mortality. We hereby describe the cytohistological and immunohistochemical features of a metastatic HV-PTC in 55-year-old male, previously diagnosed as poorly differentiated papillary thyroid carcinoma in thyroidectomy specimen. Five years after total thyroidectomy with radical neck dissection the patient presented with gross pleural effusion showing multiple lung parenchymal and pleural based lesions with complete collapse of lung on computed tomography scan. The conventional cytology of pleural fluid showed dyscohesive cells arranged in micropapillary form gave the suggestion of metastatic papillary carcinoma. But the cell block preparation highlighted >30% hobnail cells arranged in micropapillary pattern showing increased atypical mitosis and occasional pseudoinclusions. Supplemented with immunohistochemistry (CK19, TTF-1, and p53), final diagnosis HV-PTC was made.

BACKGROUND: Retiform Hemangioendothelioma (RH) is an extremely rare vascular tumor of intermediate biological behavior, which is prone to local recurrence but rarely shows metastasis to distant sites. It may harbor areas resembling Dabska tumor in some cases and angiosarcoma, which in its well differentiated form may exhibit similar pathological appearance in some areas, making it problematic to rule out a possibility of a malignant diagnosis on a core biopsy. Therefore, complete surgical resection with negative margins is essential for accurate diagnosis and local control.
RESULTS: In our series, two of the three Pakistani cases were in females, with an age range between 18 and 50 years. Our first patient presented with symptoms of cardiac compromise and pulmonary hypertension. Her computed tomography scan showed multiple tumor masses within the mediastinum. The second patient presented with an ulcerated lesion on his scalp, at right temple. The third patient presented with a hard growth on her left 4th toe which was amputated. Histologically, all cases exhibited retiform arborizing vascular spaces lined by bland endothelial cells with hobnail nuclei, characteristic of retiform hemangioendothelioma. Immunohistochemical markers CD31, CD34 and ERG confirmed the vascular nature of the tumor. The first and the second patient are alive and healthy at 4 and 7 months follow up respectively, while the third patient is lost to follow up.
CONCLUSIONS: Owing to the rate of local recurrence, RH should always be considered in the differential diagnosis of vascular tumors showing arborizing blood vessels, as it may have an atypical presentation and it should be carefully differentiated from Dabska tumor and an angiosarcoma.

Papillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid gland with most tumors behaving in an indolent fashion. However, morphologic variants have been described, such as tall cell, diffuse sclerosing, columnar cell etc. which are biologically more aggressive. One of these variants includes the more recently described hobnail variant (HVPTC) which shows micropapillae and presence of large cells with apically placed hyperchromatic nuclei, reverse polarity, and eosinophilic cytoplasm, akin to hobnail cells. The presence of >30% hobnail cells in a PTC deserves categorization as a hobnail variant. This variant is usually associated with extra thyroidal extension, lymphovascular invasion and lymph node metastasis. We describe the pathologic and molecular features of two cases of encapsulated PTC with hobnail cells in a 68 year old male and a 22 year old female (30% and 10% hobnail cells respectively). Both cases presented as low stage (pT2) tumors and showed no aggressive features like lymph node metastasis, or extrathyroidal extension (ETE) at the time of presentation. Tumors in both cases showed presence of BRAFV600E mutation, absence of RAS and/or TP53 mutations, and were negative for RET and PAX88/PPARG gene rearrangements.

Anastomosing hemangiomas are a recently recognized benign vascular neoplasm, first described by Montgomery and Epstein in 2009. A few cases have been described in the genitourinary tract, especially in the renal hilum. These are fairly well-demarcated lesions with lobules of sinusoidal-like capillaries lined by hobnail endothelial cells containing eosinophilic hyaline globules in the cytoplasm. Extramedullary hematopoiesis has been described in a few cases, along with large feeding vessels. A predominant adipocytic component has been described in only one case.[9] We describe a case of a retroperitoneal anastomosing hemangioma occurring in an extrarenal site in a 53-year-old female, followed by a review of the current literature.

Papillary thyroid carcinoma is the most common thyroid malignancy and it is usually associated with a good prognosis. However, recurrence, metastases, and cancer death may occur in 10 to 15% of patients with more aggressive types of papillary thyroid carcinoma, such as tall cell, columnar cell, solid variant, or the more recently described hobnail variant of papillary thyroid carcinoma. Papillary thyroid carcinoma with a prominent hobnail pattern is a moderately differentiated papillary thyroid carcinoma variant with aggressive clinical behavior and significant mortality. The hobnail variant of papillary thyroid carcinoma shows prominent hobnail features, which have also been referred to as micropapillary. The typical hobnail/micropapillary morphological features show loss of cellular polarity/cohesiveness and support an epithelial-mesenchymal transition as a possible mechanism of metastasis. BRAF p.V600E is the most common mutation in papillary thyroid carcinoma, including the hobnail variant; recent and continuing studies are focused on defining other molecular anomalies that may be useful for prognostic stratification and may provide therapeutic targets.

OBJECTIVE: Fine-needle aspiration (FNA) of head and neck lymph nodes (LNs) is useful in diagnosing metastatic papillary thyroid carcinoma (PTC) and most commonly shows classic cytologic features of PTC. Metastatic PTC, however, may occasionally present with a pattern unfamiliar to most pathologists: atypical histiocytoid cells (AHCs).
METHODS: All PTC thyroidectomy specimens with associated FNA of LNs were retrieved from our files for 2007 to 2013. We aimed to assess cytologic features of metastatic PTC, as well as the presence of AHCs and their morphology.
RESULTS: Fifty-six FNAs from LNs with metastatic PTC were reviewed. AHCs were identified in 38 (68%) cases, while only PTC with classic cytologic features was seen in 18 (32%) cases. AHCs did not show diagnostic nuclear features of PTC and presented as large cells with abundant cytoplasm either vacuolated or dense. Nuclei varied from vesicular with prominent nucleoli to dark and smudgy. Thirty-one cases showed mixed AHCs and classic PTC, but seven cases (13% of all metastatic PTCs in LNs) consisted only of AHCs.
CONCLUSIONS: AHCs are an often unrecognized metastatic morphologic pattern of cystic PTC, as it does not show diagnostic classic nuclear features of PTC. AHCs are the predominant cytologic finding in approximately 13% of metastatic PTCs to neck LNs.

Hobnail variant of papillary thyroid carcinoma (HPTC) represents a recently described, aggressive and rare group of thyroid tumors with poorly understood pathogenesis. Molecular data about this group of cancers are few, and a more detailed molecular characterization of these tumors is needed. The main objective of the study is to define a comprehensive molecular typing of HPTC. Eighteen patients affected by HPTC, including eighteen primary tumors and four lymph node metastases, were screened for NRAS, KRAS, HRAS, BRAF, TP53, PIK3CA, hTERT, PTEN, CDKN2A, EGFR, AKT1, CTNNB1 and NOTCH1 gene mutations. Sequencing is conducted on the MiSEQ system, and molecular data are compared with clinical-pathologic data and follow-up. The patients include 14 women and 4 men. Ages range from 23 to 87 years. All 18 primary tumors of HPTC showed ≥30% hobnail features. BRAF and TP53 mutations are by far the most common genetic alterations in primary HPTC (72.2% and 55.6%, respectively), followed by hTERT (44.4%), PIK3CA (27.8%), CTNNB1 (16.7%), EGFR (11.1%), AKT1 (5.5%) and NOTCH1 (5.5%). The mutational pattern in primary tumors and metastasis was usually maintained. Univariate Cox regression analyses with bootstrap procedure indicated a significantly increased mortality risk in patients harboring BRAF mutation and BRAF mutation associated with TP53 and/or PIK3CA mutations. The detection of these multiple mutations appears to allow the identification of a subset of more aggressive tumors within the group and to bear information that should be useful for prognostic stratification of these patients including the planning of adjuvant therapy.