Tall Columnar Cells Research Articles

Abstract PO5-27-12: TALL CELL CARCINOMA WITH REVERSED POLARITY: A RARE SUBTYPE OF INVASIVE BREAST CARCINOMA WITH UNUSUAL ONCOGENIC DRIVER MUTATION R132C IN IDH1 GENE

Abstract Introduction: Tall cell carcinoma with reversed polarity (TCCRP) is a rare subtype of invasive breast carcinoma with a distinguishing morphogical feature, which is the predilection of nuclei to polarize to the apical pole of tall columnar epithelial cells. These tumours are most commonly associated with IDH2 p.Arg172 hotspot mutations. All reported cases of TCCRP affected women ranging from 39 to 89 years (mean age of 64 years). The tumours presented as a mammographic or palpable mass, only rarely associated with axillary lymph node metastases. TCCRP are usually associated with an indolent clinical course and a favourable prognosis. Morphologically, TCCRP is composed of circumscribed nests of epithelial cells often exhibiting delicate fibrovascular cores, conveying a solid papillary pattern. True papillae and cystic structures containing colloid-like material may be observed in some cases. The tumour cells are tall and columnar, with abundant eosinophilic cytoplasm, containing bland, round to ovoid nuclei disposed at the apical pole of the columnar epithelial cells. Mitotic figures are rare. Most TCCRPs exhibit a triple-negative phenotype and a low (< 20%) Ki-67 proliferation index. Molecular features of TCCRP comprise IDH2 p.Arg172 hotspot mutations, reported in about 84% of the cases studied, as well as PIK3CA missense mutations, identified in about 68% of these tumours. Only one case of TCCRP was associated with IDH1 gene mutations according to the literature. Case report: A 62 year old woman presented with a palpable mass and no axillary adenopathy was identified. Hematoxylin-eosin (HE) stain showed an invasive breast carcinoma, with epithelial tumour cells arranged in a solid and papillary pattern with thin fibrovascular cores. Neoplastic cells are tall and columnar, with abundant eosinophilic cytoplasm and round to ovoid nuclei, exhibiting no pleomorphism and disposed in the apical pole of the cells. Mitotic figures were not detected. Considering the highly suggestive morphology on HE stain, biopsy sample was sent for molecular analysis by next generation sequencing (NGS). Results and discussion: Molecular analysis by NGS using the TruSight Oncology 500 panel (Illumina) revealed the presence of the oncogenic mutations R132C and H1047R in IDH1 and PIK3CA genes, respectively. Contrary to what occurs in almost all cases of Tall cell carcinoma with reversed polarity (TCCRP), in which an oncogenic mutation is described in codon R172 of the IDH2 gene, in this case a mutation was observed in the IDH1 gene. Such a mutation has been described in only one case diagnosed with TCCRP according to the literature, this being the second reported case. Conclusion: This case report aims to warn of the possibility that other driver mutations may be associated with the diagnosis of TCCRP, such as IDH1 R132 and not just IDH2 R172, and that a comprehensive testing approach of the IDH1/2 genes might be more accurate in these cases. Citation Format: Karla Prigenzi, Luiz Gustavo Ferreira Cortes, Paulo Vidal Campregher, João Bosco de Oliveira Filho, Nestor Andrade Piva. TALL CELL CARCINOMA WITH REVERSED POLARITY: A RARE SUBTYPE OF INVASIVE BREAST CARCINOMA WITH UNUSUAL ONCOGENIC DRIVER MUTATION R132C IN IDH1 GENE [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-27-12.

Cumin Extract Alters The Histology of Kidney and Duodenum in Adult Rabbit

Background: The current study determined the histological alterations of the kidney and duodenum due to the administration of the cumin plant. The objective of the study was how consuming cumin affects the histological structure of the kidney and duodenum. Methods: Ten healthy male rabbits were divided into two groups of five each. They were housed in the animal facility at the College of Veterinary Medicine, Kerbala University. The treatment group received an oral dose of cumin extract at 250 mg/kg body weight once daily for six weeks, while the control group was given a standard diet and water. Hematoxylin and eosin staining was used to examine tissue samples from the kidneys and duodenum. Results: The histological analysis revealed significant changes in the kidney and duodenum tissues of the rabbits treated with cumin extract. In the kidneys, there was an increase in the diameter of glomeruli and a narrower lumen of the proximal tubules, indicating increased activity. Similarly, the duodenum of the treated group exhibited taller villi and deeper crypts, suggesting enhanced absorption activity. Moreover, the arrangement of tall columnar epithelial cells in the duodenal villi was altered. Conclusion: In conclusion, high intake of cumin extract showed various histological alterations in the urinary and digestive systems, particularly in the kidney and duodenum. These findings provided insights into the potential effects of cumin consumption on organ structure and function, highlighting the need for further research to understand its implications for human health better.

AMELOBLASTOMA OF MANDIBLE: A SERIES OF SIX CASES AND REVIEW

Ameloblastoma is a benign but locally invasive odontogenic tumor with unlimited growth potential. The most common site of occurrence is mandible. Histological presentation comprises of tall columnar ameloblast like cells with central stellate reticulum showing either cystic degeneration or squamous metaplasia or cells containing granules etc. radiologically they appear as unilocular or multilocular radiolucency sometimes associated with an unerupted tooth. Here we present six cases of ameloblastoma of different histopathological variant with a short review of literature

KRAS codon 12 mutations characterize a subset of de novo proliferating “metaplastic” Warthin tumors

Warthin tumor (WT; synonym: cystadenolymphoma) represents one of the most frequent salivary gland tumors with a frequency equaling or even outnumbering that of pleomorphic adenomas in some series. Histologically, the tumor displays tall columnar oncocytic cells, arranged into two cell-thick layers lining variably cystic glands within an organoid lymphoid stroma. Tumors with exuberant squamous metaplasia in response to FNA-induced or other types of tissue injury/infarction have been referred to as “metaplastic WTs.” However, the same terminology was used for tumors with variable mucinous cell and solid or stratified epidermoid proliferations (occasionally mimicking mucoepidermoid carcinoma), although the “metaplasia concept” has never been proven for the latter. We herein investigated 22 WTs showing prominent mucoepidermoid-like or solid oncocytoma-like proliferations without prior FNA or histological evidence of infarction/ trauma using the TruSight Tumor 15 gene panel and KRAS pyrosequencing. As a control, we tested 11 conventional WTs. No statistically significant differences were observed between the two subcohorts regarding patient’s age and tumor size. Six of 22 (27%) proliferating/ metaplastic WTs revealed oncogenic KRAS mutations clustering at codon 12 (exon 2), while all conventional tumors lacked these mutations. Our findings are in line with a neoplastic nature of the epidermoid/ mucoepidermoid proliferations in non-injured “metaplastic” Warthin tumors. We propose the descriptive term “de novo proliferating Warthin tumor” for this variant to distinguish it from infarcted/inflamed genuine metaplastic Warthin tumor.

Mammary mucinous cystadenocarcinoma with long-term follow-up: molecular information and literature review

BackgroundMucinous cystadenocarcinoma (MCA) is a very rare form of breast cancer that was first described in 1998. Only 33 cases of primary MCA, including our present case, have been reported thus far. As a consequence, its molecular features, prognosis and treatment regimen are poorly known. Here, we describe a less common presentation of MCA, detail its molecular features, discuss the major differential diagnosis, and provide a brief review of the literature.Case presentationA 59-year-old woman presented with a breast lump in which mammography showed a well-defined nodule. Core needle biopsy (CNB) revealed several lesions lined by tall columnar cells with stratification and abundant mucinous secretion; excision was recommended for final diagnosis. The resected specimens showed cavities of different sizes without surrounding myoepithelial cells. The cavities were rich in mucus, and the nuclei were located at the base of the cells, containing intracellular mucus. Immunohistochemical analysis revealed that it was triple-negative breast cancer (TNBC). Next-generation sequencing (NGS) revealed pathogenic mutations in the PIK3CA, KRAS, MAP2K4, RB1, KDR, PKHD1, TERT, and TP53 genes. A diagnosis of MCA was rendered. The patient has been followed up for 108 months to date and showed no signs of recurrence or metastasis.ConclusionOur study presents the gene profile of an MCA case with no recurrence or metastatic tendency after 108 months of follow-up, and a review of the literature helps us better understand the clinical, pathologic, and molecular features of this tumor.

Granular cell ameloblastoma: A rare and unique variant

Ameloblastoma is a slow-growing and locally invasive epithelial odontogenic tumor of the jaw that runs a benign course in most cases. Granular cell ameloblastoma is a rare subtype of ameloblastoma, showing the granular transformation of its cytoplasm. It is considered as an aggressive variant of ameloblastoma. Herein, we report the case of a 34-year-old male patient who presented with a swelling in the left cheek for a 1-year duration with a recent rapid increase in size. Examination showed a 4 × 3 cm growth involving the left buccal mucosa and retromolar area. Imaging studies showed expansile lytic lesion mandible. Biopsy revealed neoplasm with odontogenic epithelial islands showing peripheral palisading of tall columnar cells with reversal of polarity and the center of the islands showing stellate reticulum-like cells which were markedly replaced by granular cells. Granular cells can appear in various odontogenic and non- odontogenic tumors. When there is extensive granular cell change in ameloblastoma, it should be differentiated from other oral lesions with granular cells including granular cell odontogenic tumor, granular cell tumor, and congenital epulis.Herein we report the case of a 34-year-old male patient presented with swelling left cheek of one-year duration with recent rapid increase in size. Examination showed a 4x3 cm growth involving left buccal mucosa and retromolar area. Imaging studies showed expansile lytic lesion mandible. Biopsy revealed neoplasm with odontogenic epithelial islands showing peripheral palisading of tall columnar cells with reversal of polarity and the center of the islands showing stellate reticulum like cells which were markedly replaced by granular cells. Granular cells can appear in various odontogenic and nonodontogenic tumors. When there is extensive granular cell change in ameloblastoma it should be differentiated from other oral lesions with granular cells including granular cell odontogenic tumour, granular cell tumour and congenital epulis.

Recurrent IDH2 Mutations in Salivary Gland Striated Duct Adenoma Define an Expanded Histologic Spectrum Distinct From Canalicular Adenoma.

Striated duct adenoma (SDA) is a rare salivary gland neoplasm defined by histologic similarity to normal striated ducts. However, doubt persists about whether SDA represents a genuine entity distinct from canalicular adenoma and if a malignant counterpart exists. This study aims to evaluate the molecular underpinnings of SDA to clarify its pathogenesis and classification. We identified 10 SDA and 2 tumors called low-grade adenocarcinoma not otherwise specified that were retrospectively recognized to resemble SDA. All cases showed recurrent histologic features including (1) discrete monophasic tubules, (2) tall columnar eosinophilic cells, (3) monotonous oval nuclei, and (4) scant fibrous stroma, and most were positive for S100 protein (91%), SOX10 (80%), and CK7 (80%). Although 1 case was previously called adenocarcinoma based on interdigitation with normal acini, this pattern was also seen in some SDA, and likely does not indicate malignancy; the significance of growth surrounding nerve in 1 other case is less clear. Targeted sequencing identified IDH2 R172X mutations in all 8 cases with sufficient tissue, with positivity for IDH1/2 mutation-specific immunohistochemistry in 9 cases stained. In contrast, 5 canalicular adenomas lacked IDH2 mutations or other oncogenic alterations. Overall, IDH2 R172X mutations are a defining feature of SDA that, in combination with its recognizable pathologic profile, confirm it is a unique entity separate from canalicular adenoma. IDH1/2 mutation-specific immunohistochemistry may provide a convenient tool to facilitate diagnosis. Both morphology and IDH2 mutations raise parallels between SDA and breast tall cell carcinoma with reverse polarity.

Rare distant metastases to pancreas, liver, and lung as initial presentation of mixed tall cell and columnar cell variants of papillary thyroid cancer.

The most common sites of distant metastases of papillary thyroid carcinoma (PTC) are lung and bone. Widespread distant metastases of PTC are rare and associated with poor overall prognosis. Metastases to sites such as liver and pancreas are extremely rare, and literature is sparse on overall survival. In this report, we present a 57-year-old man whose initial presentation of PTC was with pancreatic, liver, and lung metastases, and subsequently developed metastases to bone and brain. He underwent a total thyroidectomy, neck dissection, and tracheal resection. Pathology revealed a predominant columnar cell variant PTC with focal areas of tall cell variant, and genomic sequencing showed both PIK3CA and BRAF gene mutations. Radioactive iodine ablation with I-131 did not show any uptake in metastatic sites and he had progression of the metastases within 6 months. Therefore, therapy with lenvatinib was initiated for radioactive iodine refractory disease. Our patient has tolerated the lenvatinib well, and all his sites of metastases decreased in size. His liver and pancreatic lesions took longer to respond but showed response 6 months after initiation of lenvatinib, and he remains on full dose lenvatinib 18 months into treatment. Papillary thyroid carcinoma (PTC) usually metastasizes to lung and bone but can rarely occur in many other sites. Patients with distant metastases have significantly worse long-term prognosis. Lenvatinib can be an effective treatment of radioactive iodine refractory PTC with rare sites of distant metastases. Lenvatinib can be an effective treatment of PTC with BRAF V600E and PIK3CA mutation.

What could this dark lesion on a woman’s eyelid be?

What could this dark lesion on a woman’s eyelid be?

Morphological examination of the accessory sex glands of the Barki bucks (Capra hircus).

The present investigation was prepared to describe the accessory sex glands of the Barki bucks grossly and by light microscopy. There are four sex glands: ampullary, vesicular, prostate, and bulbourethral. The ampullary gland is an enlargement of the terminal part of the ductus deferens, its glandular part has branched tubuloalveolar glands, and its secretory alveoli lined with a pseudo-stratified epithelium composed of cuboidal to columnar cells. The vesicular gland takes the appearance of a cluster of grapes and the left vesicular gland is enlarged and higher than the right one. The vesicular gland is a lobulated tubuloalveolar gland with wide intralobular space and the gland contain a secretory unit which lined by pseudo-stratified columnar epithelium, and the interlobular ductules lined by the stratified epithelium, while the interlobular duct lined by simple cuboidal epithelium; moreover, the lining epithelium of secretory part consists of tall columnar cells. The prostate gland consists only of the disseminated part and is enclosed by a connective tissue capsule that was thin dorsally, thick laterally, and reduced in thickness ventrally. The prostatic acini are lined by simple cuboidal epithelium. The bulbourethral gland was similar in size to the walnut and surrounded by a capsule and there are interlobular connective tissue septa that divided the gland into lobes and lobules of different sizes. The bulbourethral gland contained secretory units lined by the tall simple columnar epithelium of mucous type with basely located nuclei and eosinophilic cytoplasm contains granular secretion. The gross and microscopic examination of the four accessory sex glands gave valuable information in the future pathology diagnosis of the accessory sex glands of the Barki bucks.

PRIMARY INTESTINAL-TYPE ADENOCARCINOMA OF THE TONGUE: REPORT OF A RARE CASE

Intestinal-type adenocarcinoma of the salivary glands is an exceedingly rare tumor. A 55-year-old male patient presented with an ulcerated mass in the tongue, measuring approximately 5 cm in diameter, with 2 years of evolution. The patient complained of pain. Histopathologically, the tumor presented proliferation of tall columnar cells, presenting basophilic nuclei and eosinophilic cytoplasm. Neoplastic cells were organized in anastomosing cords, showing patterns of papillary and solid growths, with duct-like structures. Cytologic and architectural features resembled those seen in well-differentiated colonic adenocarcinoma. Areas of comedonecrosis and perineural invasion were also identified. A preliminary diagnosis of adenocarcinoma was made, with 2 possibilities: intestinal-type adenocarcinoma of the salivary gland or metastatic adenocarcinoma of gastrointestinal origin. Both morphologic and immunohistochemical profiles are indistinguishable for these entities. Whole-body examination failed to identify any gastrointestinal primary tumor or that of other origins. Therefore, a gastrointestinal origin was clinically excluded. The patient was referred for cancer treatment. Intestinal-type adenocarcinoma of the salivary glands is an exceedingly rare tumor. A 55-year-old male patient presented with an ulcerated mass in the tongue, measuring approximately 5 cm in diameter, with 2 years of evolution. The patient complained of pain. Histopathologically, the tumor presented proliferation of tall columnar cells, presenting basophilic nuclei and eosinophilic cytoplasm. Neoplastic cells were organized in anastomosing cords, showing patterns of papillary and solid growths, with duct-like structures. Cytologic and architectural features resembled those seen in well-differentiated colonic adenocarcinoma. Areas of comedonecrosis and perineural invasion were also identified. A preliminary diagnosis of adenocarcinoma was made, with 2 possibilities: intestinal-type adenocarcinoma of the salivary gland or metastatic adenocarcinoma of gastrointestinal origin. Both morphologic and immunohistochemical profiles are indistinguishable for these entities. Whole-body examination failed to identify any gastrointestinal primary tumor or that of other origins. Therefore, a gastrointestinal origin was clinically excluded. The patient was referred for cancer treatment.

Limitations of fine-needle aspiration and core needle biopsies in the diagnosis of tall cell variant of papillary thyroid carcinoma.

The tall cell variant papillary thyroid carcinoma (TCV-PTC) shows aggressive behaviour. Thus far, the diagnosis of TCV-PTC can only be confirmed using the postoperative specimen. This study aims to evaluate whether fine-needle aspiration (FNA) or core needle biopsy (CNB) could diagnose TCV-PTC preoperatively. This is a retrospective cohort study. We included adult patients diagnosed with TCV-PTC or PTC with tall cell features (TCF) at final surgical pathology between January 2015 and December 2018. Preoperative histology was reviewed for six cytomorphologic features suggesting TCV-PTC in FNA or the percentage of tall cells in the CNB specimen. The postoperative pathology was also reviewed to confirm the percentage of tall cells. A total of 119 patients were included in this study; 35 (29%) patients with PTC with TCF served as controls. The most frequent cytomorphological feature in FNA samples of TCV-PTC was tall columnar cells, including single tombstone-like cells (70%). Among 43 TCV-PTC evaluated by FNA, 3 FNA (7%) revealed the absence of any of the six cytomorphologic features suggesting TCV-PTC. When we defined 30% of tall cells in CNB specimens as a cutoff suggesting TCV-PTC, only 16 (41%) TCV-PTCs could be preoperatively detected, and 3 (7%) TCV-PTCs did not have any tall cells. The proportion of tall cells was not associated with the postoperative percentage of tall cells. Both cytomorphologic features in FNA and the percentage of tall cells in CNB present limitations for use as accurate preoperative diagnostic tools of TCV-PTC.

Histological Investigation of Cyclic Variation in Secretory Activity of Seminal Vesicles in Emballonurid Bat, Taphozous kacchensis (Dobson)

The present study describes the cyclical changes in the secretory activity of the seminal vesicle in the emballonurid bat, Taphozous kacchensis. The secretory activity in the seminal vesicles during the quiescence cycle was not well marked in T. kacchensis. During the sexually quiescent period (May to August), seminal vesicles were regressed, the tubules were lined by cuboidal to low columnar epithelial cells with round to elongated darkly stained basally to centrally placed nuclei. Cytoplasm was basophilic containing fine or coarse secretory granules in the cytoplasm. The lumina of the tubules were devoid of secretion. During the pre-breeding (September to January) period, the tubules were enlarged and were lined by tall columnar epithelial cells with large spherical basally situated nucleus. The secretory blebs were seen arising from the apical surface of the cells and were seen releasing into the lumen. Lumina of the tubules were filled with homogenous eosinophilic secretion. During the breeding period (February to March), the seminal vesicle showed hypertrophy resulting in the increase in the tubular diameter as compared to that of quiescent period. The epithelial lining of the tubules was cuboidal with centrally placed nuclei. The tubular lumina were full of homogenous secretion during active pre-breeding and breeding period as the secretory material released into the lumen by both apocrine and merocrine modes. Regressive changes in the seminal vesicle were evident from April. The tubules showed gradual hypotrophy as the quiescent period approaches in May.

Morphology and seasonality of the sexual segment of the kidney in genus Bothrops snakes.

In Squamata, the sexual segment of the male kidney (SSK) produces secretory granules that are transmitted to the female tract during copulation. Here, we investigate the morphology of SSK in various species of the pitviper-genus Bothrops, a medically relevant clade of Neotropical snakes, using histology, histochemistry, as well as scanning and transmission electron microscopy. We also evaluated the relationship of SSK hypertrophy with spermatogenesis and storage of sperm. The SSK in Bothrops consists of tall columnar epithelial cells filled with electron-dense secretory granules. These granules are apparently released into the lumen by an apocrine secretory process. In general, the ultrastructural morphology of SSK in Bothrops is similar to those described for other pitvipers in the genus Agkistrodon. In most Bothrops males, the SSK produces carbohydrates and proteins, and occurs in all lobes of the kidney, occupying most of the kidney mass. In contrast, intersexual females (with male copulatory organs) of Bothrops insularis had a smaller SSK diameter than males and did not show hypertrophy. The seasonal development of SSK in Bothrops species seems to be driven by environmental factors rather than phylogeny, since sister species exhibited periods of hypertrophy at different months. In most Bothrops males, hypertrophy occurs at various seasons of the year (spring, summer, autumn), even in winter, and seasonal changes in SSK do not necessarily accompany spermatogenesis.

Recurrent Apocrine Hidrocystoma of Scalp

Sir, Hidrocystomas are rare benign cystic tumors of epidermal appendages (estimated incidence of one per thousand of submitted cutaneous biopsies) and traditionally classified into apocrine and eccrine types based on their classical histopathology and histogenesis.[12] In 1964, Mehregan first described apocrine hidrocystoma (apocrine cystadenoma) as a benign cystic adenomatous proliferation of the secretory coil of apocrine glands.[134] Postulated pathogenesis of apocrine hidrocystoma implies retention of sweat and subsequent dilation of sweat duct apparatus due to occlusion or blockage. Clinically, they appear as a solitary, cystic, well-circumscribed, dome-shaped reddish or blackish brown, nontender, skin-colored lesion measuring 3–15 mm usually between 30 and 70 years of age. Their most common site of predilection is head-and-neck region and their occurrence in the scalp is rarely reported.[15] Although usually appearing as solitary lesions, multiple apocrine hidrocystomas have rarely been described in association with Gorlin-Goltz and Schopf–Schulz–Passarge syndromes.[12] Excision biopsy and histopathology are essential for confirmation of the diagnosis. Herein, we report a rare case of recurrent apocrine hidrocystoma occurring on the scalp, an unusual site.[356] A 42-year-old female presented with a reddish-brown, nontender, well-circumscribed, gradually progressive mobile cystic swelling on the scalp measuring 3.0 cm × 2.5 cm for 6 months' duration. She gave a history of a similar lesion on the scalp about 5 years back which after surgical resection and histopathological examination was diagnosed to be apocrine hidrocystoma. No history of trauma or any other significant medical history was observed. Based on history and symptoms, a clinical diagnosis of the recurrent apocrine hidrocystoma was made and the lesion was surgically excised with clear margins which sent for histopathological examination. Macroscopic examination of skin ellipse measured 2.5 cm × 2.2 cm × 1.8 cm and contained a cyst measuring 1.6 cm in maximum dimension with a thin wall. The cyst contained minimal clear fluid and its wall was devoid of any firm nodules or papillary excrescences. Microscopic examination of hematoxylin and eosin-stained slides revealed a multilocular bilayered dermal cyst lined by an inner layer of cuboidal and tall columnar secretory cells of variable heights showing eosinophilic cytoplasm with luminal decapitation secretion, suggesting apocrine differentiation and surrounded by a peripheral layer of elongated myoepithelial cells [Figures 1 and 2]. There was no evidence of squamous or mucous metaplasia seen. There was no inflammation or cytological atypia seen. Based on characteristic histolopathogical features, a diagnosis of recurrent apocrine hidrocystoma of the scalp was made. The patient was kept on follow-up and has not reported any recurrence so far for the past 1 year.Figure 1: Multilocualted cystic lesion in the scalp showing various sized cysts (H and E stain, ×100)Figure 2: Cyst wall lined by double-layered epithelium showing the inner layer of apocrine-like secretory epithelium showing eosinophilic cytoplasm with apocrine snouts and fringes and outer layer of elongated myoepithelial cells (H and E stain, ×200)Due to their typical clinical appearance and anatomical site location, apocrine hidrocystoma must be differentiated from other similar benign lesions, such as eccrine hidrocystoma, sebaceous cyst, epidermal inclusion cyst, hemangioma, lymphangioma, and cystic basal cell epithelioma, as well as malignant lesions such as basal cell carcinoma and malignant melanoma (due to its typical blueblack color).[13456] Eccrine hidrocystoma, in particular, shares the same clinical presentation, anatomical locations, and age predilection. However, they are usually multiple lesions lined by 1–2 layered epithelial lining without any decapitation secretions and myoepithelial cells. Immunohistochemical (IHC) analysis of apocrine hidrocystoma shows positivity for human milk fat globules, gross cystic disease fluid protein 15 (GCDFP-15), cytokeratin (CK) 7, CK 8, CK 18, and CK 19 proteins in the inner layer of epithelium and alpha-smooth muscle actin (a-SMA) and p63 in the outer myoepithelial cells, while negativity for S-100 protein. Contrary to it, eccrine hidrocystoma shows positivity for CK 1, CK 5, CK 10, and CK 14 while negativity for human milk fat globules and GCDFP-15.[124567] Particularly, in long-standing apocrine hidrocystoma, IHC analysis in arriving at a correct diagnosis as increased intraluminal pressure in the cyst wall flattens them and abolishes their characteristic decapitation secretion.[7] Treatment depends on the solitary or multiple nature of the lesion and includes various medical treatment options such as anticholinergic creams, trichloroacetic acid, botulinum toxin, cryotherapy, and, carbon dioxide vaporization laser treatment, especially for multiple lesions and surgical approaches such as simple needle puncture (high chance of local recurrence), surgical excision with clear margins and electrodesiccation.[1267] Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Clinicopathological Characteristics and Recurrence-Free Survival of Rare Variants of Papillary Thyroid Carcinomas in Korea: A Retrospective Study.

BackgroundWe aimed to evaluate the clinicopathological features and biological behaviors of Korean thyroid cancer patients with rare variants of papillary thyroid carcinoma (PTC) to address the ambiguity regarding the prognostic consequences of these variants.MethodsWe retrospectively reviewed the medical records of 5,496 patients who underwent thyroid surgery for PTC, between January and December 2012, in nine tertiary hospitals. Rare PTC variants included tall cell (TCV), columnar cell (CCV), diffuse sclerosing (DSV), cribriform-morular (CMV), solid (SV), hobnail, and Warthin-like variants. Recurrence-free survival (RFS) was defined as the time from the date of thyroidectomy until recurrence.ResultsRare variants accounted for 1.1% (n=63) of the PTC patients; with 0.9% TCV, 0.02% CCV, 0.1% DSV, 0.1% CMV, and 0.1% SV. The mean age of patients and primary tumor size were 42.1±13.1 years and 1.3±0.9 cm, respectively. Extrathyroidal extension and cervical lymph node metastasis were observed in 38 (60.3%) and 37 (58.7%) patients, respectively. Ultrasonographic findings revealed typical malignant features in most cases. During a median follow-up of 7 years, 6.3% of patients experienced a locoregional recurrence. The 5-year RFS rates were 71.4% in patients with DSV or SV, 95.9% for TCV, or CCV, and 100% for other variants. DSV emerged an independent risk factor associated with shorter RFS.ConclusionIn this multicenter Korean cohort, rare variants accounted for 1.1% of all PTC cases, with TCV being the most frequent subtype. DSV emerged as a significant prognostic factor for RFS.

Sudden outbreak of metastatic intestinal adenocarcinoma in rainbow trout Oncorhynchus mykiss.

Intestinal adenocarcinomas are uncommon in fishes. To date, they have been reported in zebrafish Danio rerio, blue gularis Fundulopanchax sjostedti, koi carp Cyprinus carpio koi, Atlantic salmon Salmo salar and rainbow trout Oncorhynchus mykiss. Metastases are even rarer and have been observed so far at very low prevalence, only in feed-induced adenocarcinoma in Atlantic salmon and rainbow trout. Intestinal adenocarcinoma with liver and heart metastases and mesenteric invasion was found in approximately 33% of 4 yr old rainbow trout from a Slovene hatchery with 2000 breeding trout. During stripping, lumps in the abdominal cavity were palpated in one-third of the breeding fish; some of the fish were anorectic and lethargic, and mortality was slightly increased. Affected trout were euthanized and 4 were submitted for necropsy and histopathology. Necropsy revealed firm, whitish, irregularly lobular masses originating from the intestine. Histologically, the intestinal masses showed a prominent proliferation of tall columnar neoplastic epithelial cells arranged in dense irregular islands or solid areas and papillotubular protuberances. Solid areas of neoplastic cells were also observed in the mesentery of all trout and in the liver of one trout, whereas minute groups of neoplastic cells were seen in the vessels of the intestinal mucosa in all trout and in the myocardium and the liver of one trout. Epithelial origin of neoplastic cells was confirmed by expression of the cytokeratin marker AE1/AE3. The intestinal masses were diagnosed as intestinal adenocarcinoma with mesenteric invasion and metastases to the liver and heart. The cause of intestinal adenocarcinoma was not determined.

Responses to the First Radioactive Iodine Treatment After Targeted Therapy for Aggressive Papillary Thyroid Cancers

Introduction: Tall cell variant (TCV) and columnar cell variant (CCV) are aggressive variants of papillary thyroid cancer (PTC) and they are overrepresented in radioactive iodine (RAI) refractory cases. Studies have reported using BRAF and/or MEK inhibitors to restore iodine avidity in patients with iodine refractory disease. There is much less experience of using targeted therapy pre-emptively to enhance iodine uptake for aggressive variants and advanced disease prior to the first RAI treatment (RAI-T). We present three patients with these variants and describe their responses to the first RAI-T after targeted therapy. Case 1: 64-year-old male with CCV-PTC and areas of poor differentiation (pT3aN1bM1) has somatic BRAF V600E, TERT and AJUBA mutations. Thyroglobulin (TG) 6 weeks post surgery was 21 ug/L, with negative TG antibodies (TGAb). PET-CT revealed FDG avid superior mediastinal lymphadenopathy and lung metastases. He received dabrafenib for 6 weeks followed by his first RAI -T(153 mCi) after thyroid hormone withdrawal (THW). Pre- and post-therapy scans showed uptake in the neck, right superior mediastinum and lung metastases. Three months post RAI, TG decreased to 5.1 ug/L. Chest CT revealed stable mediastinal lymphadenopathy and decreased size of lung metastases. Case 2: 41-year-old male with TCV-PTC containing areas of focal squamous differentiation and poor differentiation (pT4aN1bM1) has somatic BRAF V600E and TP53 mutations. PET-CT showed FDG avid neck lymph nodes and lung metastases. TG 8 weeks after surgery was 1.5 ug/L, TGAb 31.19 IU/L. He was treated with dabrafenib and trametinib for 4 weeks followed by his first RAI-T (150mCi) after THW. Pretreatment scan showed uptake in the thyroid bed and cervical lymph nodes. Post-therapy scan revealed additional uptake in the lung metastases. Chest CT 3 and 9 months after RAI-T revealed stable paratracheal lymph node and lung metastases. TGAb decreased to 7.04 IU/L; TG was 2.2 ug/L. Case 3: 33-year-old female with invasive TCV-PTC (pT3bN1aM1) has a somatic BRAF V600E mutation. CT chest showed multiple scattered lung nodules up to 4mm. Ten weeks post surgery, TG was 0.1 ug/L, TGAb 5.21 IU/ml. Patient received 1 month of dabrafenib and trametinib followed by his first RAI-T(125 mCi) after THW. Pre- and post-therapy scans revealed uptake in the neck and left supraclavicular areas, without uptake in lung nodules. Three months post RAI, chest CT revealed stable lung nodules. TG was 0.1 ug/L, and TGAb was 5.16 IU/L. Neck ultrasound showed no disease. Conclusion: These three patients with aggressive variants of PTC have advanced disease, and all were found to have a BRAFV600E mutation on genomic analysis. They tolerated BRAF targeted inhibition as an attempt to enhance iodine uptake preemptively with various responses to their first RAI-T. More studies will be needed to determine if this strategy will improve outcomes for these patients.

BRAFV600E mutation is associated with aggressive features in papillary thyroid carcinomas\u2009\u2264\u20091.5\xa0cm

BackgroundWhile some studies suggest that the BRAF V600E mutation correlates with a high-risk phenotype in papillary thyroid microcarcinoma (PTMC), more evidence is necessary before this mutation can be used to help guide decision making in the management of small thyroid nodules. This study investigated whether BRAF V600E mutation is associated with aggressive features in PTMC (≤ 1 cm) and small PTC (1–1.5 cm).MethodsRetrospective chart review was performed on 121 patient cases. Patients who underwent thyroid surgery for PTMC (≤ 1 cm) or small PTC (1–1.5 cm) were included if molecular testing was done for BRAF V600E mutation. Two study groups were created based on tumour size: PTMC (n = 55) and small PTC (n = 66). The groups were analysed for the presence of a BRAF V600E mutation and aggressive features, including macroscopic extrathyroidal extension (ETE), lymph node metastasis (LNM), and high-risk histological features (tall cell, columnar cell, hobnail, solid/trabecular, and diffuse sclerosing). The Fischer exact test was used to calculate statistical significance.ResultsBRAF V600E mutations were detected in 43.6% of PTMC and 42.4% of small PTC. Of the mutated PTMC nodules, 54.1% demonstrated aggressive characteristics as compared to 19.4% of the non-mutated PTMCs (p = 0.010). Of the mutated small PTC tumours, 82.1% had aggressive features. In contrast, 28.9% of the non-mutated small PTCs showed aggressive features (p < 0.001).ConclusionsOur findings demonstrate an association between a BRAF V600E mutation and aggressive features in PTMC (≤ 1 cm) and small PTC (1–1.5 cm). Therefore, determining the molecular status of these thyroid nodules for the presence of BRAF V600E can help guide patient management.Graphical

Invasive Stratified Mucin-producing Carcinoma (ISMC) of the Cervix: A Study on Morphologic Diversity.

Invasive stratified mucin-producing carcinoma (ISMC) is a recently described tumor with similar morphology to the stratified mucin-producing intraepithelial lesion. Stratified mucin-producing intraepithelial lesion and ISMC likely arise from human papillomavirus (HPV)-infected reserve cells in the cervical transformation zone that retain their pluripotential ability to differentiate into various architectural and cytologic patterns. This is important, as small studies have suggested that ISMC may be a morphologic pattern associated with more aggressive behavior than usual HPV-associated adenocarcinoma. We sought to study the morphologic spectrum of this entity and its associations with other, more conventional patterns of HPV-associated carcinomas. Full slide sets from 52 cases of ISMC were reviewed by an international panel of gynecologic pathologists and classified according to the new International Endocervical Criteria and Classification system. Tumors were categorized as ISMC if they demonstrated stromal invasion by solid nests of neoplastic cells with at least focal areas of mucin stratified throughout the entire thickness, as opposed to conventional tall columnar cells with luminal gland formation. Tumors comprising pure ISMC, and those mixed with other morphologic patterns, were included in the analysis. Twenty-nine pure ISMCs (56%) and 23 ISMCs mixed with other components (44%) were identified. Other components included 13 cases of usual-type adenocarcinoma, 6 adenosquamous carcinoma, 3 mucinous-type adenocarcinoma, 1 high-grade neuroendocrine carcinoma. ISMC displayed architectural diversity (insular, lumen-forming, solid, papillary, trabecular, micropapillary, single cells) and variable cytologic appearance (eosinophilic cytoplasm, cytoplasmic clearing, histiocytoid features, glassy cell-like features, signet ring-like features, bizarre nuclei, squamoid differentiation). Awareness of the spectrum of morphologies in ISMC is important for accurate and reproducible diagnosis so that future studies to determine the clinical significance of ISMC can be conducted.