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A fusion between tubulin polymerization-promoting protein (TPPP), a regulatory cytoskeletal gene, and the chromatin remodeling factor, bromodomain-containing protein 9 (BRD9), TPPP-BRD9 fusion has been found in rare cancer cases, including lung and gallbladder cancers (GBC). In this study, we investigated the histopathological features of 16 GBCs previously shown by RNA sequencing to harbor the TPPP-BRD9 fusion. Findings in the fusion-positive GBCs were compared with 645 GBC cases from the authors' database. Among the 16 TPPP-BRD9 fusion-positive GBC cases, most were females (F:M = 7:1) of Chinese ethnicity (12/16), whereas the remaining cases were from Chile. The histopathological examination showed the following findings: 1) Intracholecystic neoplasm (ICN) in 7/15 (47% vs. 7% 645 reference GBCs, p < 0.001), all with gastro-pancreatobiliary phenotype, often with clear cell change, and in the background of pyloric gland metaplasia and extensive high-grade dysplasia. 2) Neuroendocrine carcinoma (NEC) morphology: 3 cases (27% vs. 4.6% in the reference database, p = 0.001) showed a sheet-like and nested/trabecular growth pattern of monotonous cells with salt-and-pepper chromatin characteristic of NECs. Two were large cell type, one had prominent clear cell features, a rare finding in GBNECs; the other one had relatively bland, well-differentiated morphology, and the remaining case was small cell type. 3) Adenocarcinoma identified in 8 cases had a distinctive pattern characterized by widely separated small, round tubular units with relatively uniform nuclei in a fashion seen in mesonephric adenocarcinomas, including hobnail-like arrangement and apical snouts, reminiscent of tubular carcinomas of the breast in many areas. In some foci, the epithelium was attenuated, and glands were elongated, some with comma shapes, which along with the mucinous/necrotic intraluminal debris created a "syringoid" appearance. 4) Other occasional patterns included the cribriform, glomeruloid patterns, and metaplastic tubular-spindle cell pattern accompanied by hemorrhage. In conclusion, TPPP-BRD9 fusion-positive GBCs often develop through intracholecystic neoplasms (adenoma-carcinoma sequence) of gastro-pancreatobiliary lineage, appear more prone to form NEC morphology and have a propensity to display clear cell change. Invasive adenocarcinomas arising in this setting often seem to display a distinctive appearance that we tentatively propose as the TPPP-BRD9 fusion-positive pattern of GBC.
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Adenocarcinoma , Carcinoma Neuroendocrino , Neoplasias de la Vesícula Biliar , Humanos , Neoplasias de la Vesícula Biliar/patología , Neoplasias de la Vesícula Biliar/genética , Femenino , Masculino , Persona de Mediana Edad , Carcinoma Neuroendocrino/patología , Carcinoma Neuroendocrino/genética , Anciano , Adenocarcinoma/patología , Adenocarcinoma/genética , Adulto , Factores de Transcripción/genética , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Fusión Génica , Proteínas del Tejido Nervioso/genética , Proteínas de Fusión Oncogénica/genéticaRESUMEN
[This corrects the article DOI: 10.1371/journal.pone.0237979.].
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The epidermal growth factor receptor (EGFR) expression is considered to play an essential role in the pathogenesis of colorectal adenocarcinoma. This study assessed the expression and predictive/prognostic value of EGFR expression in pre-op biopsy and post-op resection specimens in patients receiving neoadjuvant radiotherapy/neoadjuvant chemoradiotherapy (NRT/NCRT). Thirty-four consecutive patients were included in this study. The association between the prognostic features and EGFR immunohistochemical expression was analyzed in pre- (n=34) and post-treatment (n=22) tissue samples in cases with available tissue blocks. Of 34, 23 (67.6%) were men. The median age was 60.50 ± 10.69 (range, 31-84) years. EGFR expression was detected in 88.2% of biopsy specimens and in 91.2% of surgical specimens. There was only slight agreement between pre-op and post-op EGFR expression scores (kappa value 0.11). There was no significant correlation between pre-op and post-op EGFR expression scores (p>0.05). Although pre-op EGFR positivity and higher pre-op EGFR scores seemed to indicate a worse prognosis, this association between pre-op EGFR expression and overall survival (OS) or disease-specific survival (DSS) did not reach statistical significance (p>0.05). The only case with a post-op EGFR score of three who died of the disease experienced local recurrence and had distant metastasis. In conclusion, EGFR positivity in pre-op biopsy samples seems to be associated with shorter survival, and increased EGFR expression in post-treatment resection specimens predicts aggressive behavior in patients with rectal adenocarcinoma who received NRT/NCRT. However, due to the molecular heterogeneity, EGFR expression status should be evaluated in resection specimens rather than in pre-op biopsy samples for optimal prognosis prediction.
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OBJECTIVE: Alterations in the expression of several long non-coding RNAs (lncRNAs) have been shown in chronic hepatitis B-associated hepatocellular carcinoma (CHB-HCC). Here, we aimed to investigate the association between the expression of inflammation-associated lncRNA X-inactive specific transcript (XIST) and the type of inflammatory cells within the tumor microenvironment. MATERIAL AND METHODS: Twenty-one consecutive cirrhotic patients with CHB-HCC were included. XIST expression levels were investigated on formalin-fixed paraffin-embedded (FFPE) tumoral and peritumoral tissue samples by real-time polymerase chain reaction (RT-PCR). Immunohistochemical staining for CD3, CD4, CD8, CD25, CD163, CTLA4, and PD-1 were performed. The findings were statistically analyzed. RESULTS: Of the 21 cases, 11 (52.4%) had tumoral and 10 (47.6%) had peritumoral XIST expression. No significant association was found between the degree of inflammation and XIST expression. The number of intratumoral CD3, CD4, CD8 and CD20 positive cells was higher in XIST-expressing tumors, albeit without statistical significance. Tumoral and peritumoral XIST expression tended to be more common in patients with tumoral and peritumoral CD4high inflammation. The number of intratumoral CD25 positive cells was significantly higher in XIST-expressing tumors (p=0.01). Tumoral XIST expression was significantly more common in intratumoral CD25high cases (p=0.04). Peritumoral XIST expression was also more common among patients with CD25high peritumoral inflammation, albeit without statistical significance (p=0.19). CONCLUSION: lncRNA XIST is expressed in CHB-HCC and its expression is significantly associated with the inflammatory tumor microenvironment, particularly with the presence and number of CD25 (+) regulatory T cells. In vitro studies are needed to explore the detailed mechanism.
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Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , ARN Largo no Codificante , Linfocitos T Reguladores , Microambiente Tumoral , Humanos , ARN Largo no Codificante/genética , Microambiente Tumoral/inmunología , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virología , Carcinoma Hepatocelular/inmunología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virología , Neoplasias Hepáticas/inmunología , Masculino , Persona de Mediana Edad , Femenino , Hepatitis B Crónica/patología , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/genética , Linfocitos T Reguladores/inmunología , Adulto , AncianoRESUMEN
PURPOSE: To assess dry eye disease characteristics of pediatric patients with diabetes. METHODS: Twenty-one patients with type-1 diabetes mellitus (DM), 20 with type-2 DM, 19 with maturity-onset diabetes of the young (MODY), and 20 control participants were included in the study. Ocular Surface Disease Index (OSDI) questionnaire, tear film break-up time (TBUT) analysis, Schirmer test with anesthesia, and conjunctival impression cytologic analysis were performed. RESULTS: In Group 1, the Schirmer test and TBUT values were lower than the control group. In groups 1 to 3, OSDI scores were higher than the control group. In Groups 1 and 2, the goblet cell density was lower than the control group. CONCLUSIONS: Dry eye parameters of all three diabetic groups were adversely affected in favor of dry eye disease. Children with MODY have increased OSDI scores. Alterations in the conjunctival impression cytology were observed more prominently in patients with type-1 DM.
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Diabetes Mellitus Tipo 2 , Síndromes de Ojo Seco , Humanos , Niño , Diabetes Mellitus Tipo 2/complicaciones , Lágrimas , Células Caliciformes , Síndromes de Ojo Seco/diagnóstico , Síndromes de Ojo Seco/etiologíaRESUMEN
CONTEXT.: The nature and associations of gallbladder (GB) "adenomyoma" (AM) remain controversial. Some studies have attributed up to 26% of GB carcinoma to AMs. OBJECTIVE.: To examine the true frequency, clinicopathologic characteristics, and neoplastic changes in GB AM. DESIGN.: Cholecystectomy cohorts analyzed were 1953 consecutive cases, prospectively with specific attention to AM; 2347 consecutive archival cases; 203 totally embedded GBs; 207 GBs with carcinoma; and archival search of institutions for all cases diagnosed as AM. RESULTS.: Frequency of AM was 9.3% (19 of 203) in totally submitted cases but 3.3% (77 of 2347) in routinely sampled archival tissue. A total of 283 AMs were identified, with a female to male ratio = 1.9 (177:94) and mean size = 1.3 cm (range, 0.3-5.9). Most (96%, 203 of 210) were fundic, with formed nodular trabeculated submucosal thickening, and were difficult to appreciate from the mucosal surface. Four of 257 were multifocal (1.6%), and 3 of 257 (1.2%) were extensive ("adenomyomatosis"). Dilated glands (up to 14 mm), often radially converging to a point in the mucosa, were typical. Muscle was often minimal, confined to the upper segment. Nine of 225 (4%) revealed features of a duplication. No specific associations with inflammation, cholesterolosis, intestinal metaplasia, or thickening of the uninvolved GB wall were identified. Neoplastic change arising in AM was seen in 9.9% (28 of 283). Sixteen of 283 (5.6%) had mural intracholecystic neoplasm; 7 of 283 (2.5%) had flat-type high-grade dysplasia/carcinoma in situ. Thirteen of 283 cases had both AM and invasive carcinoma (4.6%), but in only 5 of 283 (1.8%), carcinoma arose from AM (invasion was confined to AM, and dysplasia was predominantly in AM). CONCLUSIONS.: AMs have all the features of a malformative developmental lesion, and may not show a significant muscle component (ie, the name "adeno-myoma" is partly a misnomer). While most are innocuous, some pathologies may arise in AMs, including intracholecystic neoplasms, flat-type high-grade dysplasia or carcinoma in situ, and invasive carcinoma (1.8%, 5 of 283). It is recommended that gross examination of GBs include serial slicing of the fundus for AM detection and total submission if one is found.
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Adenomioma , Carcinoma in Situ , Carcinoma , Neoplasias de la Vesícula Biliar , Humanos , Masculino , Femenino , Vesícula Biliar/patología , Adenomioma/diagnóstico , Adenomioma/patología , Carcinoma/patología , Neoplasias de la Vesícula Biliar/patología , Carcinoma in Situ/patología , Hiperplasia/patologíaRESUMEN
OBJECTIVE: Pediatric skin diseases may show various manifestations, occasionally affecting the patients' quality of life. Histopathological examination may be required for the diagnosis. The aim of this study was to evaluate the spectrum of clinicopathological features in pediatric skin lesions. MATERIAL AND METHOD: A total of 368 biopsies of 359 consecutive patients were included. The clinicopathological findings were retrospectively evaluated. Non-neoplastic (inflammatory) lesions (ILs) (n=186) were grouped per their origin, while neoplastic/proliferative lesions (NPLs) (n=182) were grouped based on their pattern. The clinical and histopathological characteristics were statistically analyzed. RESULTS: 51% were male and the median age was 10.4±4.9 years (range 0-17). ILs mainly involved the head and neck, and NPLs were mostly located in the lower extremity (p < 0.001). The most common NPLs were benign nevus (18%, n=33) and pilomatrixoma (15%, n=27), while the most frequent IL was spongiotic/psoriasiform dermatitis (38%). Skin appendage/connective tissue tumors were the largest among NPLs (p=0.02). NPLs were more frequently seen in children > 12 years old compared to ILs (p=0.03). The discordance rate between clinical and histopathological diagnoses was higher for NPLs (27% vs. 15%). CONCLUSION: Although the spectrum of skin lesions is broad in pediatric patients, most are benign in nature. The higher frequency of melanocytic and/or cystic lesions among children > 12 years old may be attributed to increased self-care during puberty. Neoplastic/proliferative lesions of childhood seem to be less commonly recognized by clinicians, and a multidisciplinary approach remains the optimal method, considering the relatively high rate of discordance between the clinical and histopathological diagnoses.
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Calidad de Vida , Neoplasias Cutáneas , Humanos , Niño , Masculino , Recién Nacido , Lactante , Preescolar , Adolescente , Femenino , Estudios Retrospectivos , Neoplasias Cutáneas/patología , Piel/patología , BiopsiaRESUMEN
Medullary carcinomas have not yet been fully characterized in the ampulla. Here, 359 ampullary carcinomas (ACs) were reviewed and 11 medullary-type carcinomas (3%) were found and analyzed. In addition to the diagnostic medullary pattern, 6 showed focal mucinous and 8 had focal abortive gland-like formations. They occurred in younger patients (57 versus 65 y; P = .02), had larger invasion size (mean, 3.2 versus 1.9 cm; P = .01), formed nodular polypoid or plaque-like tumors, and often lacked preinvasive component. In addition to the lymphoplasmacytic infiltrates, they also had prominent eosinophils in 5 of 11 cases. Eight were papilla Vateri-NOS (not otherwise specified) tumors, 2 were ampullary-duodenal origin, 1 had a minor intra-ampullary papillary tubular neoplasm component, and none were ampullary-ductal. Although they had pushing-border infiltration, perineural and vascular invasion was common. They were strongly associated with DNA mismatch repair (MMR) protein deficient (7/11, 64%). The 5-yr survival rate (53%) appeared to be comparable with, and perhaps even better than that of nonmedullary ACs (47%), although this did not reach statistical significance (P = .47). Programmed cell death ligand-1 (PD-L1) expression levels were assessed in 8, and all 4 that were MMR deficient were positive both by combined positive score (CPS) ≥1 and tumor proportion score (TPS) ≥1, and of the 4 MMR proficient cases, 3 were positive by CPS; 2 by TPS. Overall, only 1 of the 8 available for analysis failed to show PD-L1 positivity by CPS. In contrast, nonmedullary MMR-deficient carcinomas expressed PD-L1 in only 33% of tumors by CPS, and none by TPS. One medullary carcinoma was also EBV associated. Unlike 'medullary carcinomas' of the kidney, INI1 was retained in all 8 cases tested. In conclusion, medullary carcinomas are 3% of ACs, have a strong association with MMR-D, and may be less aggressive despite their larger size. PD-L1 expression appears to be closely associated with medullary ACs regardless of MMR status, and thus targeted therapies can be considered for all medullary carcinomas of this site.
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Carcinoma Medular , Carcinoma Neuroendocrino , Neoplasias del Conducto Colédoco , Neoplasias Duodenales , Neoplasias Pancreáticas , Humanos , Antígeno B7-H1/análisis , Biomarcadores de Tumor/análisis , Carcinoma Medular/genética , Neoplasias del Conducto Colédoco/genética , Neoplasias del Conducto Colédoco/patología , Reparación de la Incompatibilidad de ADN , Inestabilidad de MicrosatélitesRESUMEN
Among the mass-forming preinvasive (tumoral intraepithelial) neoplasms of the biliary tract, intraductal tubulopapillary neoplasms (ITPN-Bs) are increasingly being recognized as a separate category. By being intramucosal polypoid proliferations of dysplastic/neoplastic cells, they are highly similar to other members of the "intraductal neoplasms (IDNs)" category (namely, intraductal papillary neoplasms [IPNBs], and intraductal oncocytic papillary neoplasms [IOPNs]); however, they are distinguished by MUC6-expressing nonmucinous cells that lack intestinal differentiation and form striking tubular configuration. Their molecular/genetic profile is also proving to be different with frequent alterations in cell cycle and chromatin remodeling genes, which are quite uncommon in other IDNs and cholangiocarcinomas. Despite the conceptual overlaps, they are also very different from intracholecystic nonmucinous tubular neoplasms (ICTN) of the gallbladder with the latter being associated with Wnt/beta-catenin pathway alterations, and almost never invasive. In contrast, ITPN-Bs are invasive in an estimated 80% of the cases, although even invasive examples often exhibit a protracted course. Invasive carcinomas arising from ITPN-Bs are overall similar to cholangiocarcinomas (including small duct and large duct patterns) but also often have peculiar characteristics such as more nodular-compact (blunt invasion) pattern. Like other IDNs, the ITPN-Bs have also been classified in the past as intraductal-spreading type of cholangiocarcinomas (and they are still regarded as such in some publications). In small biopsies, they are prone to be mistaken as ordinary adenocarcinomas because of their tubular pattern and pancreatobiliary cytology although their relatively monotonous cytology and zones of back-to-back tubule formation can help in their correct identification. Clinical presentation of ITPN-Bs is generally similar to other intraductal neoplasms; however, in the intrahepatic component, they tend to be more nodular than cystic, and their snake-like intraductal growth pattern is often more striking. In the management (diagnosis and treatment) of these tumors that are in essence adenoma-carcinoma sequence, the invasive and noninvasive components ought to be evaluated separately. Minimally invasive examples are commonly curable, and even those more extensively invasive may have a surprisingly good prognosis. In summary, biliary ITPNs form a distinct category not only clinicopathologically, immunophenotypically, and molecular-wise but regarding their biological behavior as well.
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Adenocarcinoma , Neoplasias de los Conductos Biliares , Carcinoma Ductal Pancreático , Colangiocarcinoma , Neoplasias Pancreáticas , Humanos , Diagnóstico Diferencial , Conductos Biliares/patología , Adenocarcinoma/patología , Vesícula Biliar/patología , Colangiocarcinoma/diagnóstico , Neoplasias de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/patología , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/patologíaRESUMEN
There are highly conflicting data on relative frequency (2-32%), prognosis, and management of pT1b-gallbladder carcinoma (GBC), with 5-year survival ranging from > 90% in East/Chile where cholecystectomy is regarded as curative, versus < 50% in the West, with radical operations post-cholecystectomy being recommended by guidelines. A total of 473 in situ and invasive extensively sampled GBCs from the USA (n = 225) and Chile (n = 248) were re-evaluated histopathologically per Western invasiveness criteria. 349 had invasive carcinoma, and only 24 were pT1. Seven cases previously staged as pT1b were re-classified as pT2. There were 19 cases (5% of all invasive GBCs) qualified as pT1b and most pT1b carcinomas were minute (< 1mm). One patient with extensive pTis at margins (but pT1b focus away from the margins) died of GBC at 27 months, two died of other causes, and the remainder were alive without disease (median follow-up 69.9 months; 5-year disease-specific survival, 92%). In conclusion, careful pathologic analysis of well-sampled cases reveals that only 5% of invasive GBCs are pT1b, with a 5-year disease-specific survival of > 90%, similar to findings in the East. This supports the inclusion of pT1b in the "early GBC" category, as is typically done in high-incidence regions. Pathologic mis-staging of pT2 as pT1 is not uncommon. Cases should not be classified as pT1b unless extensive, preferably total, sampling of the gallbladder to rule out a subtle pT2 is performed. Critical appraisal of the literature reveals that the Western guidelines are based on either SEER or mis-interpretation of stage IB cases as "pT1b." Although the prognosis of pT1b-GBC is very good, additional surgery (radical cholecystectomy) may be indicated, and long-term surveillance of the biliary tract is warranted.
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Carcinoma in Situ , Carcinoma , Neoplasias de la Vesícula Biliar , Humanos , Neoplasias de la Vesícula Biliar/patología , Colecistectomía , Carcinoma in Situ/patología , Carcinoma/patología , Estadificación de Neoplasias , Estudios RetrospectivosRESUMEN
ABSTRACT Purpose: To investigate subjective ocular symptoms and objectively measure tear secretion in patients with a confirmed diagnosis of coronavirus disease-2019 (COVID-19). Methods: In this prospective cross-sectional study, 24 patients who had survived COVID-19 infection and 27 healthy controls were enrolled. Conjunctival impression cytology, the Schirmer test, tear-film break-up time, corneal staining scores were applied to all the participants. Results: No significant difference was noted with regard to the gender and mean age between the two groups (p=0.484 and p=0.599, respectively). The conjunctival impression cytology analysis revealed that the density of the goblet cells was decreased, while the counts of lymphocytes and neutrophils were increased in the COVID-19 group patients when compared with ethe control group patients. When the Nelson classification was applied to the conjunctival impression cytology samples, 25% of the COVID-19 group patients and 14.8% of the control group patients exhibited changes consistent with ≥grade 2. The mean tear-film break-up time, Schirmer test, and corneal staining score results were determined to differ between the COVID-19 and control groups (p=0.02, p<0.001, and p=0.003, respectively). Conclusions: The present study revealed the pathological conjunctival alterations of patients with a confirmed diagnosis of COVID-19, indicating the possibility of the occurrence of pathological ocular surface alterations to even at the end of COVID-19 infection, without the occurrence of any significant clinical ocular manifestations.
RESUMO Objetivo: Investigar sintomas oculares subjetivos e medir a secreção lacrimal objetivamente em pacientes com diagnóstico confirmado da doença coronavírus 2019 (COVID-19). Métodos: Vinte e quatro pacientes que sobreviveram à infecção pela COVID-19 e 27 controles saudáveis foram incluídos neste estudo transversal prospectivo. Citologia de impressão da conjuntiva, teste de Schirmer, tempo de separação do filme lacrimal, pontuações de coloração da córnea foram aplicados a todos os participantes. Resultados: Concluiu-se que não houve diferença significativa em relação ao gênero e idade média entre os dois grupos (p=0,484 e p=0,599, respectivamente). A análise dos resultados da citologia de impressão da conjuntiva revelou que a densidade das células do cálice diminuiu, enquanto os linfócitos e neutrófilos aumentaram nos pacientes do grupo COVID-19 quando comparados com os do grupo controle. Quando a classificação de Nelson foi aplicada às amostras de citologia de impressão da conjuntiva, determinou-se que 25% dos pacientes do grupo COVID-19 e 14,8% dos pacientes do grupo controle apresentaram alterações consistentes com grau 2 ou superior. O tempo médio de separação do filme lacrimal, teste de Schirmer e os resultados das pontuações de coloração da córnea foram determinados, diferindo entre o grupo COVID-19 e o grupo controle (p=0,02, p<0,001, and p=0,003, respectivamente). Conclusões: As análises realizadas neste estudo revelaram as alterações conjuntivais patológicas de pacientes com diagnóstico confirmado de COVID-19 e mostraram que é possível que alterações patológicas da superfície ocular ocorram mesmo no final da infecção pela COVID-19, sem a ocorrência de manifestações oculares clínicas significativas.
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The literature on liver cysts is highly conflicting, mostly owing to definitional variations. Two hundred and fifty-eight ≥1 cm cysts evaluated pathologically using updated criteria were classifiable as: I. Ductal plate malformation related (63%); that is, cystic bile duct hamartoma or not otherwise specified-type benign biliary cyst (35 with polycystic liver disease). These were female predominant (F/M=2.4), large (10 cm), often multifocal with degenerative/inflammatory changes and frequently misclassified as "hepatobiliary cystadenoma." II. Neoplastic (13%); 27 (10.5%) had ovarian-type stroma (OTS) and qualified as mucinous cystic neoplasm (MCN) per World Health Organization (WHO). These were female, solitary, mean age 52, mean size 11 cm, and 2 were associated with carcinoma (1 in situ and 1 microinvasive). There were 3 intraductal papillary neoplasms, 1 intraductal oncocytic papillary neoplasm, 1 cystic cholangiocarcinoma, and 2 cystic metastasis. III. Infectious/inflammatory (12%). These included 23 hydatid cysts (including 2 Echinococcus alveolaris both misdiagnosed preoperatively as cancer), nonspecific inflammatory cysts (abscesses, inflammatory cysts: 3.4%). IV. Congenital (7%). Mostly small (<3 cm); choledochal cyst (5%), foregut cyst (2%). V. Miscellaneous (4%). In conclusion, hepatic cysts occur predominantly in women (3/1), are mostly (90%) non-neoplastic, and seldom (<2%) malignant. Cystic bile duct hamartomas and their relative not otherwise specified-type benign biliary cysts are frequently multifocal and often misdiagnosed as "cystadenoma/carcinoma." Defined by OTS, MCNs (the true "hepatobiliary cystadenoma/carcinoma") are solitary, constitute only 10.5% of hepatic cysts, and have a significantly different profile than the impression in the literature in that essentially all are perimenopausal females, and rarely associated with carcinoma (7%). Since MCNs can only be diagnosed by demonstration of OTS through complete microscopic examination, it is advisable to avoid the term "cystadenoma/cystadenocarcinoma" solely based on radiologic examination, and the following simplified terminology would be preferable in preoperative evaluation to avoid conflicts with the final pathologic diagnosis: (1) noncomplex (favor benign), (2) complex (in 3 subsets, as favor benign, cannot rule out malignancy, or favor malignancy), (3) malignant features.
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Neoplasias de los Conductos Biliares , Quiste del Colédoco , Cistadenocarcinoma , Cistoadenoma , Neoplasias Pancreáticas , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/patología , Quiste del Colédoco/patología , Cistadenocarcinoma/patología , Cistoadenoma/patología , Quistes , Diagnóstico Diferencial , Femenino , Humanos , Hepatopatías , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/patologíaRESUMEN
PURPOSE: To investigate subjective ocular symptoms and objectively measure tear secretion in patients with a confirmed diagnosis of coronavirus disease-2019 (COVID-19). METHODS: In this prospective cross-sectional study, 24 patients who had survived COVID-19 infection and 27 healthy controls were enrolled. Conjunctival impression cytology, the Schirmer test, tear-film break-up time, corneal staining scores were applied to all the participants. RESULTS: No significant difference was noted with regard to the gender and mean age between the two groups (p=0.484 and p=0.599, respectively). The conjunctival impression cytology analysis revealed that the density of the goblet cells was decreased, while the counts of lymphocytes and neutrophils were increased in the COVID-19 group patients when compared with ethe control group patients. When the Nelson classification was applied to the conjunctival impression cytology samples, 25% of the COVID-19 group patients and 14.8% of the control group patients exhibited changes consistent with ≥grade 2. The mean tear-film break-up time, Schirmer test, and corneal staining score results were determined to differ between the COVID-19 and control groups (p=0.02, p<0.001, and p=0.003, respectively). CONCLUSIONS: The present study revealed the pathological conjunctival alterations of patients with a confirmed diagnosis of COVID-19, indicating the possibility of the occurrence of pathological ocular surface alterations to even at the end of COVID-19 infection, without the occurrence of any significant clinical ocular manifestations.
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PURPOSE: The aim of this study was to investigate tear function-associated clinical findings and conjunctival histopathological changes in children with vitamin D (Vit-D) deficiency. METHODS: This study used a prospective case-control design. Group 1 (n=38) comprised pediatric patients with Vit-D deficiency, and group 2 (n=45) was the control group. Tear break-up times (TBUTs), Schirmer-1 test measurements, ocular surface disease index (OSDI) scores, and conjunctival impression cytology (CIC) results of the groups were compared. RESULTS: The participant demographic characteristics, including the mean age and the male-to-female ratio, were similar (P>0.05). The median TBUT and Schirmer-1 test measurement were 10 s (5-15) and 12 mm (6-19) in group 1 and 11 s (6-16) and 15 mm (8-21) in group 2 (P=0.004 and P=0.013, respectively). The median OSDI scores were 16 (10-20) in group 1 and 17 (10-21) in group 2 (P=0.092). According to the CIC, 25 samples in group 1 and 40 samples in group 2 were categorized as grade 0, 11 samples in group 1 and 5 samples in group 2 were categorized as grade 1, and 2 samples in group 1 and no sample in group 2 were categorized as grade 2 (P=0.027). CONCLUSION: Significant conjunctival histopathological changes occur in children with Vit-D deficiency, and these changes have effects on some tear function-associated clinical findings including the Schirmer-1 test and TBUT measurements.
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Síndromes de Ojo Seco , Deficiencia de Vitamina D , Estudios de Casos y Controles , Niño , Conjuntiva/patología , Síndromes de Ojo Seco/etiología , Síndromes de Ojo Seco/patología , Femenino , Humanos , Masculino , Estudios Prospectivos , LágrimasRESUMEN
Data on peritumoral histopathologic findings in patients with hepatocellular carcinoma (HCC) is limited. In this retrospective study, we evaluated the peritumoral histopathologic changes in patients with chronic viral hepatitis (CVH)-associated HCC (CVH-HCC) and their prognostic value. 61 consecutive cirrhotic patients who underwent liver transplantation due to CVH-HCC were included. Histopathologic features within 1 cm distance of the tumor, and their association with clinicopathological characteristics and prognosis were evaluated. A random representative slide of cirrhotic parenchyma unrelated to invasive and/or dysplastic foci was also evaluated for the same histopathologic criteria. The majority (85%, n = 52) were male with a median age of 55 ± 6.38 (range, 39-67). The etiologic agent was only HBV in 90% (n = 55). The most common peritumoral findings were portal inflammation (100%; n = 61), ductular reaction (100%; n = 61) and sinusoidal dilatation (95%; n = 58). Macrovascular invasion was observed only in four cases (7%) with mild peritumoral portal inflammation. Neutrophilic infiltration of the peritumoral portal tracts (n = 18; 30%) was significantly associated with pT4 tumor stage, tumor grade, macrovascular invasion, and pretransplant therapy. Patients with moderate or severe peritumoral sinusoidal dilatation tended to have worse prognosis, albeit not significantly. Peritumoral ballooning degeneration was associated with multifocality, recurrence and recurrence-free survival in both uni- and multivariate analysis. Peritumoral histopathologic changes in CVH-HCC can be classified as: changes related to pathogenesis, changes indirectly affecting prognosis, and changes directly affecting prognosis. Peritumoral prominent ballooning degeneration may be a predictor of recurrence while portal neutrophilic infiltration and sinusoidal dilatation seem to indicate poor prognosis.
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Carcinoma Hepatocelular , Hepatitis Viral Humana , Neoplasias Hepáticas , Carcinoma Hepatocelular/patología , Femenino , Hepatitis Viral Humana/complicaciones , Humanos , Inflamación , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/patología , Masculino , Recurrencia Local de Neoplasia , Pronóstico , Estudios RetrospectivosRESUMEN
OBJECTIVE: To determine the associations of pancreatobiliary maljunction (PBM) in the West. BACKGROUND: PBM (anomalous union of common bile duct and pancreatic duct) is mostly regarded as an Asian-only disorder, with 200X risk of gallbladder cancer (GBc), attributed to reflux of pancreatic enzymes. Methods: Radiologic images of 840 patients in the US who underwent pancreatobiliary resections were reviewed for PBM and contrasted with 171 GBC cases from Japan. RESULTS: Eight % of the US GBCs (24/300) had PBM (similar to Japan; 15/ 171, 8.8%), in addition to 1/42 bile duct carcinomas and 5/33 choledochal cysts. None of the 30 PBM cases from the US had been diagnosed as PBM in the original work-up. PBM was not found in other pancreatobiliary disorders. Clinicopathologic features of the 39 PBM-associated GBCs (US:24, Japan:15) were similar; however, comparison with non-PBM GBCs revealed that they occurred predominantly in females (F/M = 3); at younger (<50-year-old) age (21% vs 6.5% in non-PBM GBCs; P = 0.01); were uncommonly associated with gallstones (14% vs 58%; P < 0.001); had higher rate of tumor-infiltrating lymphocytes (69% vs 44%; P = 0.04); arose more often through adenoma-carcinoma sequence (31% vs 12%; P = 0.02); and had a higher proportion of nonconventional carcinomas (21% vs 7%; P = 0.03). Conclusions: PBM accounts for 8% of GBCs also in the West but is typically undiagnosed. PBM-GBCs tend to manifest in younger age and often through adenoma-carcinoma sequence, leading to unusual carcinoma types. If PBM is encountered, cholecystectomy and surveillance of bile ducts is warranted. PBM-associated GBCs offer an invaluable model for variant anatomy-induced chemical (reflux-related) carcinogenesis.
Asunto(s)
Neoplasias de la Vesícula Biliar , Neoplasias Gastrointestinales , Conductos Biliares , Carcinogénesis/patología , Conducto Colédoco/anomalías , Conducto Colédoco/diagnóstico por imagen , Conducto Colédoco/patología , Femenino , Neoplasias de la Vesícula Biliar/etiología , Neoplasias de la Vesícula Biliar/patología , Neoplasias Gastrointestinales/patología , Humanos , Persona de Mediana Edad , Conductos Pancreáticos/diagnóstico por imagen , Conductos Pancreáticos/patologíaRESUMEN
The advancing edge profile is a powerful determinant of tumor behavior in many organs. In this study, a grading system assessing the tumor-host interface was developed and tested in 181 pancreatic neuroendocrine tumors (PanNETs), 63 of which were <=2 cm. Three tumor slides representative of the spectrum (least, medium, and most) of invasiveness at the advancing edge of the tumor were selected, and then each slide was scored as follows. Well-demarcated/encapsulated, 1 point; Mildly irregular borders and/or minimal infiltration into adjacent tissue, 2 points; Infiltrative edges with several clusters beyond the main tumor but still relatively close, and/or satellite demarcated nodules, 3 points; No demarcation, several cellular clusters away from the tumor, 4 points; Exuberantly infiltrative pattern, scirrhous growth, dissecting the normal parenchymal elements, 5 points. The sum of the rankings on the three slides was obtained. Cases with scores of 3-6 were defined as "non/minimally infiltrative" (NI; n = 77), 7-9 as "moderately infiltrative" (MI; n = 68), and 10-15 as "highly infiltrative" (HI; n = 36). In addition to showing a statistically significant correlation with all the established signs of aggressiveness (grade, size, T-stage), this grading system was found to be the most significant predictor of adverse outcomes (metastasis, progression, and death) on multivariate analysis, more strongly than T-stage, while Ki-67 index did not stand the multivariate test. As importantly, cases <=2 cm were also stratified by this grading system rendering it applicable also to this group that is currently placed in "watchful waiting" protocols. In conclusion, the proposed grading system has a strong, independent prognostic value and therefore should be considered for integration into routine pathology practice after being evaluated in validation studies with larger series.
Asunto(s)
Tumores Neuroendocrinos , Neoplasias Pancreáticas , Humanos , Clasificación del Tumor , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/patología , PronósticoRESUMEN
The literature is highly conflicted on what percentage of pancreatic ductal adenocarcinomas (PDACs) arise in association with intraductal papillary mucinous neoplasms (IPMNs). Some studies have claimed that even small (Sendai-negative) IPMNs frequently lead to PDAC. Recently, more refined pathologic definitions for mucin-lined cysts were provided in consensus manuscripts, but so far there is no systematic analysis regarding the frequency and clinicopathologic characteristics of IPMN-mimickers, i.e., pseudo-IPMNs. In this study, as the first step in establishing frequency, we performed a systematic review of the pathologic findings in 501 consecutive ordinary PDACs, which disclosed that 10% of PDACs had associated cysts ≥1 cm. While 31 (6.2%) of these were IPMN or mucinous cystic neoplasm (MCN), 19 (3.8%) were other cyst types that mimicked IPMN (pseudo-IPMNs) per recent WHO/consensus criteria. As the second step of the study, we performed a comparative clinicopathologic analysis by also including our entire surgical pathology/consultation databases that was comprised of 60 IPMN-associated PDACs, 30 MCN-associated PDACs and 40 pseudo-IPMN-associated PDACs. We found that 84% of true IPMNs were pre-operatively recognized, whereas IPMN was considered in differential diagnosis of 33% of pseudo-IPMNs. Of the 40 pseudo-IPMNs, there were 15 secondary duct ectasias; 6 large-duct-type PDACs; 5 pseudocysts; 5 cystic tumor necrosis; 4 simple mucinous cysts; 3 groove pancreatitis-associated paraduodenal wall cysts; and 2 congenital cysts. Microscopically, pseudo-IPMNs had at least partial mucinous-lining mimicking IPMN but had smaller cystic (mean = 1.9 cm) and larger PDAC (mean = 3.8 cm) components compared to true IPMNs (cyst = 5.7 cm; PDAC = 2.0 cm). In summary, in this pathologically verified analysis that utilized refined criteria, 10% of PDACs were discovered to have cysts ≥1 cm, about two-thirds of which were IPMN/MCN but about one-third were pseudo-IPMNs. True IPMNs underlying the PDACs are often large and are already diagnosed pre-operatively as having an IPMN component, whereas only a third of the pseudo-IPMNs receive IPMN diagnosis by imaging and their cysts are smaller. At the histopathologic level, pseudo-IPMNs are highly prone to misdiagnosis as IPMN, which presumably accounts for much higher association of IPMNs with PDAC as reported in some studies. The subtle but salient characteristics of pseudo-IPMNs elucidated in this study should be combined with careful radiological/clinical correlation in order to exclude pseudo-IPMNs.
Asunto(s)
Carcinoma Ductal Pancreático/complicaciones , Carcinoma Ductal Pancreático/diagnóstico , Neoplasias Intraductales Pancreáticas/complicaciones , Neoplasias Intraductales Pancreáticas/diagnóstico , Adenocarcinoma/complicaciones , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de los Conductos Biliares/complicaciones , Neoplasias de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/patología , Carcinoma Ductal Pancreático/patología , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Intraductales Pancreáticas/patología , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patología , Neoplasias PancreáticasRESUMEN
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, painful disease with a 5-year survival rate of only 9%. Recent evidence indicates that distinct epigenomic landscapes underlie PDAC progression, identifying the H3K9me pathway as important to its pathobiology. Here, we delineate the role of Euchromatic Histone-lysine N-Methyltransferase 2 (EHMT2), the enzyme that generates H3K9me, as a downstream effector of oncogenic KRAS during PDAC initiation and pancreatitis-associated promotion. EHMT2 inactivation in pancreatic cells reduces H3K9me2 and antagonizes Kras G12D -mediated acinar-to-ductal metaplasia (ADM) and Pancreatic Intraepithelial Neoplasia (PanIN) formation in both the Pdx1-Cre and P48 Cre/+ Kras G12D mouse models. Ex vivo acinar explants also show impaired EGFR-KRAS-MAPK pathway-mediated ADM upon EHMT2 deletion. Notably, Kras G12D increases EHMT2 protein levels and EHMT2-EHMT1-WIZ complex formation. Transcriptome analysis reveals that EHMT2 inactivation upregulates a cell cycle inhibitory gene expression network that converges on the Cdkn1a/p21-Chek2 pathway. Congruently, pancreas tissue from Kras G12D animals with EHMT2 inactivation have increased P21 protein levels and enhanced senescence. Furthermore, loss of EHMT2 reduces inflammatory cell infiltration typically induced during Kras G12D -mediated initiation. The inhibitory effect on Kras G12D -induced growth is maintained in the pancreatitis-accelerated model, while simultaneously modifying immunoregulatory gene networks that also contribute to carcinogenesis. This study outlines the existence of a novel KRAS-EHMT2 pathway that is critical for mediating the growth-promoting and immunoregulatory effects of this oncogene in vivo, extending human observations to support a pathophysiological role for the H3K9me pathway in PDAC.
RESUMEN
Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine cancer that shows aggressive biological behaviour. Although it usually occurs on sun-exposed areas, it can sometimes be seen on non-sun-exposed sites. Here, we present the case of a 66-year-old woman with MCC arising from the right gluteal region that was treated with excision and adjuvant chemoradiotherapy. On follow-up after the 24 months, the patient was disease- and recurrence-free, representing the longest survival among patients with gluteal MCC. Early diagnosis and treatment are important to improve survival rates in patients with non-sun-exposed MCC.