Malignant Infiltration Research Articles

Gastrointestinal bleeding in critically ill immunocompromised patients

BackgroundAcute gastrointestinal bleeding (GIB) may be a severe condition in immunocompromised patients and may require intensive care unit (ICU) admission. We aimed to describe the clinical spectrum of critically ill immunocompromised patients with GIB and identify risk factors associated with mortality and severe GIB defined by hemorrhagic shock, hyperlactatemia and/or the transfusion of more than 5 red blood cells units. Finally, we compared this cohort with a control population of non-immunocompromised admitted in ICU for GIB.ResultsRetrospective study in 3 centers including immunocompromised patients with GIB admitted in ICU from January, 1st 2010 to December, 31rd 2019. Risk factors for mortality and severe GIB were assessed by logistic regression. Immunocompromised patients were matched with a control group of patients admitted in ICU with GIB. A total of 292 patients were analyzed in the study, including 141 immunocompromised patients (compared to a control group of 151 patients). Among immunocompromised patients, upper GIB was more frequent (73%) than lower GIB (27%). By multivariate analysis, severe GIB was associated with male gender (OR 4.48, CI95% 1.75–11.42, p = 0.00), upper GIB (OR 2.88, CI95% 1.11–7.46, p = 0.03) and digestive malignant infiltration (OR 5.85, CI95% 1.45–23.56, p = 0.01). Conversely, proton pump inhibitor treatment before hospitalization was significantly associated with decreased risk of severe GIB (OR 0.25, IC95% 0.10–0.65, p < 0.01). Fifty-four patients (38%) died within 90 days. By multivariate analysis, mortality was associated with hemorrhagic shock (OR 2.91, IC95% 1.33–6.38, p = 0 .01), upper GIB (OR 4.33, CI95% 1.50–12.47, p = 0.01), and long-term corticosteroid therapy before admission (OR 2.98, CI95% 1.32–6.71, p = 0.01). Albuminemia (per 5 g/l increase) was associated with lower mortality (OR 0.54, IC95% 0.35–0.84, p = 0.01). After matching with a control group of non-immunocompromised patients, severity of bleeding was increased in immunocompromised patients, but mortality was not different between the 2 groups.ConclusionMortality is high in immunocompromised patients with GIB in ICU, especially in patients receiving long term corticosteroids. Mortality of GIB is not different from mortality of non-immunocompromised patients in ICU. The prophylactic administration of proton pump inhibitors should be considered in this population.

Ultrasound Elastography for the Evaluation of Lymph Nodes.

The differential diagnosis of lymphadenopathy is important for predicting prognosis, staging, and monitoring the treatment, especially for cancer patients. Conventional computed tomography and magnetic resonance imaging characterize lymph node (LN) with disappointing sensitivity and specificity. Conventional ultrasound with the advantage of high resolution has been widely used for the LN evaluation. Ultrasound elastography (UE) using color map or shear wave velocity can non-invasively demonstrate the stiffness and homogeneity of both the cortex and medulla of LNs and can detect early circumscribed malignant infiltration. There is a need of a review to comprehensively discuss the current knowledge of the applications of various UE techniques in the evaluation of LNs. In this review, we discussed the principles of strain elastography and shear wave-based elastography, and their advantages and limitations in the evaluation of LNs. In addition, we comprehensively introduced the applications of various UE techniques in the differential diagnosis of reactive LNs, lymphoma, metastatic LNs, and other lymphadenopathy. Moreover, the applications of endoscopic UE and endobronchial UE are also discussed, including their use for improving the positive rate of diagnosis of fine-needle aspiration biopsy.

Duodenal monomorphic epitheliotropic intestinal T cell lymphoma along with unpredictable intestinal Epstein-Barr virus infection; a rare newly redefined entity in a rare site and review of literature

Introduction: Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), previously known as type II enteropathy associated T-cell lymphoma (EATL), was redefined by the WHO (2016) as separate entity from the celiac disease-associated lymphoma. It is an extremely rare and highly aggressive peripheral T-cell lymphoma. It mainly involves jejunum and ileum and rarely duodenum. Case Presentation: This was a 38-year-old male patient presented by daily vomiting related to meals for 8 months along with generalized colicky abdominal pain associated with constipation and marked weight loss. Upper endoscopy showed large ulcerated mass at the third part of the duodenum. Histopathological examination showed the diffuse malignant lymphoid infiltrate with morphology and immunophenotyping consistent with MEITL associated with unpredictable Epstein-Barr virus (EBV) in intestinal epithelial cells. The patient underwent five cycles of chemotherapy (cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone) followed by duodenectomy. Conclusion: This case represents a rare newly redefined lymphoma entity in a rare site associated with unpredictable non-neoplastic epithelial EBV infection, which proved to be oncogenic agent involved in various hematopoietic and other neoplasms with unclear relationship to the development of this MEITL.

Intratumoral T cells have a differential impact on FDG-PET parameters in follicular lymphoma

Data on the prognostic impact of pretherapy 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in follicular lymphoma (FL) is conflicting. The predictive utility of pretherapy total metabolic tumor volume (TMTV) and maximum standardized uptake value (SUVmax) on outcome appears to vary between regimens. Chemoimmunotherapies vary in the extent of T-cell depletion they induce. The role of intratumoral T cells on pretherapy FDG-PET parameters is undefined. We assessed pretherapy FDG-PET parameters and quantified intratumoral T cells by multiple methodologies. Low intratumoral T cells associated with approximately sixfold higher TMTV, and FL nodes from patients with high TMTV showed increased malignant B-cell infiltration and fewer clonally expanded intratumoral CD8+ and CD4+ T-follicular helper cells than those with low TMTV. However, fluorescently labeled glucose uptake was higher in CD4+ and CD8+ T cells than intratumoral B cells. In patients with FDG-PET performed prior to excisional biopsy, SUVmax within the subsequently excised node associated with T cells but not B cells. In summary, TMTV best reflects the malignant B-cell burden in FL, whereas intratumoral T cells influence SUVmax. This may contribute to the contradictory results between the prognostic role of different FDG-PET parameters, particularly between short- and long-term T-cell-depleting chemoimmunotherapeutic regimens. The impact of glucose uptake in intratumoral T cells should be considered when interpreting pretherapy FDG-PET in FL.

NONSEMINOMATOUS GERM CELL TUMOR METASTATIC TO THE MAXILLA

<h3>Background</h3> Extragonodal germ cell tumors (GCTs) primarily affect the sacrococcygeal region. Head and neck GCT is rare and accounts for 3% of pediatric neoplasms. Only isolated cases of metastatic GCT have been reported. <h3>Objective</h3> To report a unique case of a metastatic nonseminomatous GCT of mixed phenotype with yolk sac tumor, embryonal carcinoma, and immature teratoma components. <h3>Clinical Findings</h3> A 13-year-old male patient presented with a rapidly enlarging, painless right maxillary tuberosity mass, present for 4 months. The tumor was on the buccal gingiva extending to the hard and soft palate posteriorly. Ipsilateral submandibular lymphadenopathy was evident. No pathology was noted on the panelipse and periapical radiographs. The clinical impression was that of a lymphoma or Kaposi sarcoma. <h3>Pathologic Findings</h3> The histology showed an extensively infiltrative high-grade malignancy composed of small, round, blue discohesive tumor cells demonstrating a solid growth pattern, with areas of adenocarcinoma and squamous differentiation with keratinization. Surface dysplasia was not present. Brisk mitotic activity was noted. Immunohistochemistry revealed positivity with for AE1/AE3, SALL4, Glyplican 3, and OCT3/4, confirming the diagnosis of a metastatic nonseminomatous GCT of mixed phenotype. <h3>Summary</h3> Benign teratomas are the most common childhood extragonodal tumors, followed by yolk sac tumors, which frequently arise in the ovaries and testis. Yolk sac tumors that frequently arise in the ovaries and testis have been reported but continue to be a rare extragonodal tumor and are difficult to diagnose. This report reviews germ cell tumors in the spectrum of metastatic disease to the oral cavity.

Local recurrence of iodine refractory thyroid cancers. Surgicaltherapy options for larynx and trachea infiltration

Local recurrence of thyroid carcinomas can result in tumor infiltration in the lower region of the larynx. Since these tumors typically no longer store iodine, treatment options are greatly limited. The present study describes our experience with laryngo-tracheal resection of such cases of local recurrence. From July 2019 to November 2020, we treated five patients with malignant infiltration of the trachea and larynx due to local recurrence of a thyroid carcinoma. We performed laryngo-tracheal resection with end-to-end anastomosis in four patients and frontolateral partial laryngectomy in one patient. The median length of hospital stay was 6 days (5-14). An R0 resection was performed in two patients. Problems with the anastomosis or bilateral recurrent laryngeal nerve paralysis was not seen in any of the patients. One patient had to be reintubated on the second postoperative day due to lung failure. He was able to be extubated after five days. High tracheal resection with partial resection of the larynx was able to be performed with minimal risk. Although radical resections are rare, they expand oncological treatment options in the case of local recurrence of thyroid carcinomas that are iodine-refractory. High tracheal resection could be part of the oncological treatment spectrum in the case of local recurrence of thyroid carcinomas that no longer store iodine.

Gastric Mixed Neuroendocrine-Nonneuroendocrine Neoplasm: A rare case report

Objective: The incidence of gastric neuroendocrine neoplasms is less than 1%. They are seen as combined tumors with non-neuroendocrine neoplasms at a rate of approximately 7%. This study aims to share the case of mixed neuroendocrine and non-neuroendocrine cancer with the literature.&#x0D; Case: Endoscopic biopsies were taken from the tumoral mass detected in the gastric cardia region at endoscopy in a 60-year-old male patient that has complaints of weight loss and epigastric pain. Histopathological examination revealed malignant tumor infiltration that consisting of neuroendocrine cells with large nuclei and narrow cytoplasm in some areas and adenoid structures composed of atypical cells with pleomorphic large nuclei in some areas. Strong staining was observed in neuroendocrine areas with neuroendocrine markers such as synaptophysin and Chromogranin. Ki-67 proliferative index and mitotic activity were high in neuroendocrine neoplasm areas. The case was reported as a high-grade neuroendocrine-non neuroendocrine mixed neoplasm.&#x0D; Conclusion: Gastric Mixed Neuroendocrine-Nonneuroendocrine neoplasms are rare cases and correct diagnosis and grading are important in the treatment and patient follow-up protocol.

Corpus Callosum Remodeling in Glioma: Constancy of Fiber Density and Anisotropy in MRI.

Corpus callosum (CC) is the primary fiber system bridging the cerebral hemispheres and is of critical importance for glioma migration which downgrades the prognosis. Here we present the specific pattern of CC restructuring in glioma patients. We probe that the magnetic resonance imaging-based fiber count decrease can be a ready noninvasive indicator of glioma aggressivity and prognosis. We find that to maintain the callosal neural transmission efficiency, the optimum architectural density of white matter fibers remains unchanged, even though there is gross fiber loss. This adaptation occurs by CC's isotonic restructuration, a protective compensatory behavior for maintaining CC's optimal functional efficiency despite malignant infiltration.

Activated Regulatory T-Cells, Dysfunctional and Senescent T-Cells Hinder the Immunity in Pancreatic Cancer.

Simple SummaryPancreatic cancer has the worst survival of any human cancer. Checkpoint blockade has not yielded much benefit in pancreatic cancer. We explored immune cell phenotypes with this disease to identify new targets for checkpoint blockade therapy. We created a checkpoint-focused panel to analyse immune cells from eight pancreatic cancer patients. This showed us the majority of T-cells are senescent. Further T-cell investigation demonstrated the majority of cytotoxic T-cells have intermediate to low PD1 expression suggesting why PD1 may not work as a pancreatic cancer therapy strategy. Our data has also highlighted a regulatory T-cell population which is highly activated and can mediate immunosuppression. The checkpoints that are highly expressed on these cells are TIGIT, ICOS and CD39, suggesting inhibition of these may be a viable therapeutic strategy. Furthermore, we showed that Tregs were retained amongst the fibroblast stroma of the tumour. Our work suggests there are key checkpoints on Tregs that may help guide therapeutic strategies in pancreatic cancer.Pancreatic cancer has one of the worst prognoses of any human malignancy and leukocyte infiltration is a major prognostic marker of the disease. As current immunotherapies confer negligible survival benefits, there is a need to better characterise leukocytes in pancreatic cancer to identify better therapeutic strategies. In this study, we analysed 32 human pancreatic cancer patients from two independent cohorts. A multi-parameter mass-cytometry analysis was performed on 32,000 T-cells from eight patients. Single-cell RNA sequencing dataset analysis was performed on a cohort of 24 patients. Multiplex immunohistochemistry imaging and spatial analysis were performed to map immune infiltration into the tumour microenvironment. Regulatory T-cell populations demonstrated highly immunosuppressive states with high TIGIT, ICOS and CD39 expression. CD8+ T-cells were found to be either in senescence or an exhausted state. The exhausted CD8 T-cells had low PD-1 expression but high TIGIT and CD39 expression. These findings were corroborated in an independent pancreatic cancer single-cell RNA dataset. These data suggest that T-cells are major players in the suppressive microenvironment of pancreatic cancer. Our work identifies multiple novel therapeutic targets that should form the basis for rational design of a new generation of clinical trials in pancreatic ductal adenocarcinoma.

Mesopancreatic excision for pancreatic ductal adenocarcinoma improves local disease control and survival

BackgroundSurvival in ductal adenocarcinoma of the pancreatic head (hPDAC) is poor. After implementation of the circumferential resection margin (CRM) into standard histopathological evaluation, the margin negative resection rate has drastically dropped. However, the impact of surgical radicality on survival and the influence of malignant infiltration of the mesopancreatic fat remains unclear. At our institution, a standardized dissection of the mesopancreatic lamina and peri-pancreatic vessels are obligatory components of radical pancreatoduodenectomy. The aim of our study was to histopathologically analyze mesopancreatic tumor infiltration and the influence of CRM-evaluated resection margin on relapse-free and overall survival. MethodClinicopathological and survival parameters of 264 consecutive patients who underwent surgery for hPDAC were evaluated. ResultsThe rate of R0 resection R0(CRM-) was 48.5%, after the implementation of CRM. Mesopancreatic fat infiltration was evident in 78.4% of all consecutively treated patients. Patients with mesopancreatic fat infiltration were prone to lymphatic metastases (N1 and N2) and had a higher rate of positive resection margin (R1/R0(CRM+)). In multivariate analysis, only R0 resection was shown to be an independent prognostic parameter. Local recurrence was diagnosed in only 21.1% and was significantly lower in patients with R0(CRM-) resected hPDACs (10.9%, p < 0.001). ConclusionMesopancreatic excision is justified, since mesopancreatic fat invasion was evident in the majority of our patients. It is associated with a significantly improved local tumor control as well as longer relapse-free and overall survival.

Invited Commentary: Infiltrative Growth Pattern in Renal Malignancy-A Clue to Diagnosis and Prognosis.

Invited Commentary: Infiltrative Growth Pattern in Renal Malignancy-A Clue to Diagnosis and Prognosis.

Tertiary lymphoid tissue in early\u2010stage IgG4-related tubulointerstitial nephritis incidentally detected with a tumor lesion of the ureteropelvic junction: a case report

BackgroundIgG4-related kidney disease causes renal impairment of unknown pathogenesis that may progress to kidney failure. Although ectopic germinal centers contribute to the pathogenesis of the head and neck lesions of IgG4-related disease, the presence of tertiary lymphoid tissue (TLT) containing germinal centers in IgG4-RKD has rarely been reported. Case presentationWe report a 72-year-old Japanese man who had IgG4-related tubulointerstitial nephritis (TIN) with TLT formation incidentally detected in a resected kidney with mass lesion of IgG4-related ureteritis in the ureteropelvic junction. During follow-up for past surgical resection of a bladder tumor, renal dysfunction developed and a ureter mass was found in the right ureteropelvic junction, which was treated by nephroureterectomy after chemotherapy. Pathology revealed no malignancy but abundant IgG4-positive cell infiltration, obliterative phlebitis and storiform fibrosis, confirming the diagnosis of IgG4-related ureteritis. In the resected right kidney, lymphoplasmacytes infiltrated the interstitium with focal distribution in the renal subcapsule and around medium vessels without storiform fibrosis, suggesting the very early stage of IgG4-TIN. Lymphocyte aggregates were also detected at these sites and consisted of B, T, and follicular dendritic cells, indicating TLT formation. IgG4-positive cells infiltrated around TLTs.ConclusionsOur case suggests that TLT formation is related with the development of IgG4-TIN and our analysis of distribution of TLT have possibility to elucidate IgG4-TIN pathophysiology.

Infiltrative Renal Malignancies: Imaging Features, Prognostic Implications, and Mimics.

Infiltrative renal malignancies are a subset of renal masses that are morphologically characterized by a poorly defined interface with the renal parenchyma. Infiltrative renal malignancies are less common but more aggressive than more typical renal malignancies and carry an overall worse prognosis. Although an infiltrative renal process often represents a malignant neoplasm, infiltrative masses include a wide spectrum of diseases including primary renal cortical, medullary, and pelvic tumors; lymphoproliferative processes; metastases; and various infectious, inflammatory, immune-mediated, and vascular mimics. The imaging features of these masses are often nonspecific, but with the appropriate history, laboratory results, and clinical context, the radiologist can help narrow the diagnosis and guide further treatment. An invited commentary by Lee is available online.Online supplemental material is available for this article. ©RSNA, 2021.

Pediatric bone marrow alterations

The age-dependent development of the bone marrow follows aconstant pattern and has an impact on the localization and morphology of various bone marrow processes. Physiological, reactive and benign bone marrow alterations must be differentiated from inflammatory or malignant infiltrations. In many cases, aspecific age distribution pattern and typical morphological characteristics in magnetic resonance imaging (MRI) enable adiagnostic classification. The only adequate imaging modality that can provide information about the bone marrow composition is MRI.

Abdominal ultrasound and its significant role in colon cancer. The advantage of its dynamic nature: using respiratory movements to assess neoplasia relations to adjacent organs.

A 58-year-old, otherwise healthy male presented to the Emergency Room due to a 24-hour-long bloody diarrhea and constitutional syndrome. Colonoscopy confirmed the presence of a colonic neoplasia. A CT scan revealed an irregular surface and poorly delimited hypodensity of liver segment 5, next to the neoplasia, with malignant infiltration being impossible to rule out.

Malignant Psoas Syndrome Demonstrated by PET/CT in the Context of Metastatic Non Small Cell Lung Cancer

The significant cancer pain syndrome of malignant psoas syndrome (MPS), was first reported as a neurooncologic occurrence in 1990. The Syndrome is characterised by malignant infiltration of a psoas muscle, either directly or by involvement with haematogenously disseminated metastatic cancer. Direct involvement has been from primary tumours of the psoas muscle, or by extension from malignant paraaortic lymphadenopathy. Treatment is difficult, complex analgesia is essential, and benefits have been achieved from chemotherapy, radiotherapy and in select cases, surgery. Here, the case of a 60 year old female who presented with three months of moderate dyspnoea, low back and left inguinal region pain/numbness and lassitude, is reported. Chest radiograph and CT showed a large anterior mediastinal mass. FDG PET/CT revealed the mass to be intensely avid, with heterogeneous central areas of photopaenia. Avid lymphadenopathy was also present in two mediastinal nodal stations. Subdiaphragmatically, there was a metabolically FDG avid soft tissue mass in the superior part of the left psoas muscle, presumably accounting for her pain. There was no FDG avidity elsewhere. Core biopsy of the psoas mass revealed adenocarcinoma of probable lung origin. The patient responded symptomatically to intermediate dose radiation therapy. The pathophysiology of MPS is discussed and the range of cancer types associated with the Syndrome is updated.

Endoscopic ultrasound-guided gallbladder drainage as a rescue therapy for unresectable malignant biliary obstruction: a multicenter experience.

Endoscopic retrograde cholangiopancreatography (ERCP) is often unsuccessful in patients with duodenal stenosis or malignant ampullary infiltration. While endoscopic ultrasound-guided biliary drainage (EUS-BD) has been proposed as an alternative, EUS-guided gallbladder drainage (EUS-GBD) is an attractive option when both approaches fail. We aimed to assess the effectiveness and safety of EUS-GBD as rescue therapy for malignant distal bile duct obstruction. A multicenter retrospective study was performed on patients with unresectable malignant distal bile duct obstruction who underwent EUS-GBD between 2014 and 2019 after unsuccessful ERCP and EUS-BD. Clinical success was defined as a decrease in serum bilirubin of > 50 % within 2 weeks. 28 patients were included, with a lumen-apposing metal stent used in 26 (93 %) and a self-expandable metal stent in two (7 %). The technical success rate was 100 %. The clinical success rate was 93 %, with an improvement in bilirubin (7.3 [SD 5.4] pre-procedure vs. 2.8 [SD 1.1] post-procedure; P = 0.001). Delayed adverse events included food impaction of the stent (n = 3), with a further two patients developing cholecystitis and bleeding. This study demonstrates the feasibility of gallbladder drainage to relieve malignant distal bile duct obstruction in patients with failed ERCP and EUS-BD.

The value of virtual bronchoscopic navigation and radial endobronchial ultrasound-guided transbronchial lung cryobiopsies for pulmonary lymphangitic carcinomatosis.

BackgroundPulmonary lymphangitic carcinomatosis (PLC) is characterized by malignant infiltration into lung lymphatic channels from a primary site and is often observed in advanced malignant tumors. This study aimed to evaluate the diagnostic yield of transbronchial lung cryobiopsy in PLC guided by radial endobronchial ultrasound and virtual bronchoscopic navigation (VBN).MethodsThis prospective study enrolled 40 patients with clinical and radiologic features indicating PLC. The radial endobronchial ultrasound probe was initially advanced to the region of interest of the desired lobe near the pleura with guidance by VBN. Transbronchial lung biopsy and transbronchial lung cryobiopsy were both performed in the same ROI of all patients with the obtained samples being sent to the pathology laboratory for diagnostic analysis. Procedural complications were recorded.ResultsThe average number of transbronchial lung biopsy and transbronchial lung cryobiopsy specimens were 4 (3 to 6) and 2 (1 to 3), respectively (t=10.43, P<0.01), with the corresponding mean diameters per biopsy being 3.7 and 8.7 mm (t=12.37, P<0.01). The diagnostic yields of transbronchial lung biopsy and transbronchial lung cryobiopsy were 70% (28/40) and 92.5% (37/40), respectively. The final positive predictive values of transbronchial lung cryobiopsy and transbronchial lung biopsy for PLC were 94.4% (34/36) and 77.8% (28/36), respectively (χ2=23.94, P<0.01). Further, 52.2% (12/23) and 81.5% (22/27) of the patients in the transbronchial lung biopsy and transbronchial lung cryobiopsy groups, respectively, were diagnosed with non-small lung cancer after further molecular analysis (χ2=19.56, P<0.01). Only 2 (5%) cases presented postoperative pneumothorax. Moreover, 0 (0%), 3 (7.5%), and 17 (42.5%) patients presented severe, moderate, and mild bleeding, respectively. There were no other adverse events or deaths.ConclusionsTransbronchial lung cryobiopsy with the guidance of radial endobronchial ultrasound and VBN without fluoroscopy has a good diagnostic yield for PLC; moreover, it allows one to obtain adequate and intact tissue samples for further molecular analysis.

T-cell receptor antibodies expression in benign and malignant cutaneous lymphoid infiltrates in comparison with T-cell receptor gene rearrangement and its diagnostic utility in borderline cases

IntroductionCutaneous T-cell lymphoid infiltrate can represent reactive lesion or a malignant T-cell lymphoma. However, clinical and histopathological appearance can overlap in both groups with a risk of misdiagnosis. Aberrant expression of T-cell markers is not always applicable and T-cell receptor (TCR) gene rearrangement is not always accessible and diagnosis in borderline cases can be challenging. AimsSeveral types of TCR antibodies are currently available with limited knowledge of their expression in different cutaneous lymphoid infiltrates. Aim of the study is a comparison of expression of TCR antibodies in benign and malignant lymphoid infiltrates and their utility in borderline cases. MethodsRepresentative cases of reactive and malignant lymphoproliferations were collected. Separate group of lesions with borderline morphology was selected for comparison. Immunohistochemical expression of TCR-V-betaF1 (TCRBF1), TCR-C-beta1 (TCRJOVI.1), TCR gamma/delta (TCRGD) and TCR delta (TCRD) was performed in all cases. TCR gene rearrangement evaluation was performed in all cases using PCR BIOMED-2 assay. ResultsBenign lymphoid infiltrates were all negative in TCRD and TCRGD. Expression of TCRJOVI.1 was seen in 3/10 cases and TCRBF1 in one. T-cell lymphomas were positive for TCRBF1 and TCRGD in 60% and 30% of cases respectively. TCR gene rearrangement was confirmed in 90% of lymphoma cases. All benign lesions were polyclonal. Morphologically borderline lesions showed expression of TCRBF1 in 6/10 cases and TCR gene rearrangement in 4/10 cases. Re-evaluation of the cases and clinical correlation led to the change of the diagnosis and confirmation of T-cell lymphoma in 4/10 cases. ConclusionsExpression of TCRBF1 and TCR-gene rearrangement was significantly associated with malignant infiltrates. TCRBF1 positivity in borderline cutaneous lymphoproliferations can raise the suspicion of malignancy but confirmation by TCR gene rearrangement and careful clinical correlation is still advisable.

Identification of PKP 2/3 as potential biomarkers of ovarian cancer based on bioinformatics and experiments

BackgroundPlakophilins (PKPs) are widely involved in gene transcription, translation, and signal transduction, playing a crucial role in tumorigenesis and progression. However, the function and potential mechanism of PKP1/2/3 in ovarian cancer (OC) remains unclear. It’s of great value to explore the expression and prognostic values of PKP1/2/3 and their potential mechanisms, immune infiltration in OC.MethodsThe expression levels, prognostic values and genetic variations of PKP1/2/3 in OC were explored by various bioinformatics tools and databases, and PKP2/3 were selected for further analyzing their regulation network and immune infiltration. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathways (KEGG) enrichment were also conducted. Finally, the expression and prognosis of PKP2 were validated by immunohistochemistry.ResultsThe expression level and prognosis of PKP1 showed little significance in ovarian cancer, and the expression of PKP2/3 mRNA and protein were upregulated in OC, showing significant correlations with poor prognosis of OC. Functional enrichment analysis showed that PKP2/3 and their correlated genes were significantly enriched in adaptive immune response, cytokine receptor activity, organization of cell–cell junction and extracellular matrix; KEGG analysis showed that PKP2/3 and their significantly correlated genes were involved in signaling pathways including cytokine-mediated signaling pathway, receptor signaling pathway and pathways in cancer. Moreover, PKP2/3 were correlated with lymphocytes and immunomodulators. We confirmed that high expression of PKP2 was significantly associated with advanced stage, poor differentiation and poor prognosis of OC patients.ConclusionMembers of plakophilins family showed various degrees of abnormal expressions and prognostic values in ovarian cancer. PKP2/3 played crucial roles in tumorigenesis, aggressiveness, malignant biological behavior and immune infiltration of OC, and can be regarded as potential biomarker for early diagnosis and prognosis evaluation in OC.