A combined deep-penetrating tumour redefined as WNT-activated deep-penetrating/plexiform melanocytoma (DPM), may pose challenging clinical and histological diagnoses.
To review the ...clinicopathological characteristics of combined DPMs and characterize the molecular profile of atypical and malignant forms.
The study included 51 patients with combined DPMs diagnosed at the Hospital Clinic of Barcelona and the University of Florence between 2012 and 2020. Clinical data, dermoscopy images (when available) and histological characteristics were reviewed. Immunohistochemistry for β-catenin, LEF1, HMB45, Ki67, p16 and PRAME (preferentially expressed antigen in melanoma) was performed. Atypical forms underwent next-generation sequencing (NGS) panel analysis, including driver genes implicated in DPMs, TERT-promoter (p) mutations and the investigation of the 9p21 locus via fluorescence in situ hybridization.
Among the 51 patients (32 females and 19 males, age range 4-74 years), 68% with available clinical data (15/22) were initially suspected of having melanoma. Except for one patient, complete excision resulted in no recurrences or metastases. One patient who had an incompletely excised combined DPM developed a lymph node melanoma metastasis 10 years later. In the 51 patients, 10 samples (20%) showed atypical histological features; 7 (14%) exhibited a significant loss of p16 expression; and 2 (4%) showed a high-proliferative index (Ki67 over 5%). NGS analysis in 11 patients revealed a double mutation BRAFV600E and exon 3 CTNNB1; no TERTp mutations were detected.
Clinical suspicion of melanoma is common in combined DPMs, but malignant progression is infrequent in tumours lacking high-grade atypia or proliferation. These findings are congruent with the consideration of these lesions as intermediate-grade tumours or melanocytomas.
Extranodal NK/T-cell lymphoma (ENKTL), nasal type, may be of NK or T-cell origin; however, the proportion of T-ENKTLs and whether they are of αβ or γδ type remains uncertain. To elucidate the cell of ...origin and detailed phenotype of ENKTL and assess any clinicopathologic associations, 67 cases of ENKTL from Thailand were investigated, together with 5 γδ enteropathy-associated T-cell lymphomas (EATLs) for comparison. In all, 70% of the ENKTL were T-cell receptor (TCR) β,γ and, in cases tested, δ negative (presumptive NK origin); 5% were TCR γδ, 3% were TCR αβ, 1% were TCR αβ/γδ, and 21% were indeterminate. Out of 17 presumptive NK-ENKTLs tested, 3 had clonal TCR rearrangements. All cases were EBV and TIA-1; >85% were positive for CD3, CD2, granzyme B, pSTAT3, and Lsk/MATK; and all were CD16. Presumptive NK-ENKTLs had significantly more frequent CD56 (83% vs. 33%) and CXCL13 (59% vs. 0%) but less frequent PD-1 (0% vs. 40%) compared with T-ENKTLs. Of the NK-ENKTLs, 38% were Oct-2 compared with 0% of T-ENKTLs, and 54% were IRF4/MUM1 compared with 20% of T-ENKTLs. Only αβ T-ENKTLs were CD5. Intestinal ENKTLs were EBV and had significantly more frequent CD30, pSTAT3, and IRF4/MUM1 expression but less frequent CD16 compared with γδ EATL. Significant adverse prognostic indicators included a primary non-upper aerodigestive tract site, high stage, bone marrow involvement, International Prognostic Index ≥2, lack of radiotherapy, Ki67 >40%, and CD25 expression. The upper aerodigestive tract ENKTLs of T-cell origin compared with those of presumptive NK origin showed a trend for better survival. Thus, at least 11% of evaluable ENKTLs are of T-cell origin. Although T-ENKTLs have phenotypic and some possible clinical differences, they share many similarities with ENKTLs that lack TCR expression and are distinct from intestinal γδ EATL.
Background. Calciphylaxis is not uniquely observed in uraemic patients, as some cases have also been reported in patients with normal renal function or moderate chronic kidney disease (CKD), in ...association with severe vasculopathy or systemic inflammation. A particular subset worthy of studying is represented by those patients who develop calciphylaxis after kidney transplantation (KT). Methods. Analysis of the local series of calciphylaxis after KT (n = 14) along with all the other cases reported in the literature from 1969 to 2019 (n = 31), for a total population of 45 patients, is presented. Demographic data, CKD history, risk factors, immunosuppression, clinical presentation and management have been analysed both as a whole and according to the time period (before or after the year 2000). Results. Calciphylaxis developed during the first year after KT in 43.2% of patients and median (interquartile range) creatinine at diagnosis was 2.4 (1.25-4.64) mg/dL. The most frequent presentation included distal purpura or ulcers in one-third of cases and 39.1% of patients were receiving vitamin K antagonists. PTH values were above 500 pg/mL and below 100 pg/mL in 50.0% and 25.0% of cases, respectively. Whole population mortality was 55.6%. As expected, clinical presentation, immunosuppression and management varied depending on the time period. Patients diagnosed after 2000 were older, with longer dialysis vintage, and treatment was usually multimodal; on the contrary, in patients diagnosed before 2000, parathyroidectomy was the treatment of choice in 61.9% of cases. Conclusions. Calciphylaxis can still occur after KT, in many cases during the first year and in patients with a good renal function. Risk factors and management varied according to the time period studied. Keywords: bisphosphonates, calcific uraemic arteriolopathy, calcification, calcineurin inhibitors, calciphylaxis, cinacalcet, immunosuppression, kidney transplantation, parathyroidectomy, sodium thiosulphate
The aims of the study were to investigate and compare the immunophenotype of tumor-infiltrating lymphocytes (TILs) and PD-L1 expression in a series of benign, intermediate and malignant Spitzoid ...lesions showing marked inflammatory lymphoid component, to find out its possible relation with the prognosis of these lesions.
Six out of 97 Spitz nevus (SN) (6 %), five out of 26 atypical Spitz tumors (AST) (16 %) and seven out of 37 Spitzoid melanomas (SM) (19 %) showed diffuse, intense inflammatory component and were included in the study. The biological risk of the tumors was assessed in all AST through the melanoma 4 probe-FISH assay and the 9p21 locus exploration. TILs were quantitatively immunophenotyped using CD3, CD4, CD8, CD20, TIA1, FOXP3 and PD1 antibodies. PD-L1 was assessed in tumoral cells and inflammatory cells adjacent to the tumor.
No significant differences of TILs immunophenotype were found between SN, AST and SM. However, the classification of tumors according to the biological risk showed that grouped SN plus low-risk AST had a significantly higher number of T-cells CD8+ and TIA-1+, as well as a lower CD4/CD8 relation and B- lymphocyte number than high-risk of progression tumors (grouped high-risk AST plus SM). Immunoregulatory T-cell markers PD1 and FOXP3 only correlated with each other and with PD-L1 expression.
In conclusion, The TILs immunoprofile differences between low-risk and high-risk of progression Spitzoid tumors, especially regarding CD8 and the cytotoxic immune response, can add prognostic information about these challenging tumors and impact the clinical management of patients.
•High-grade tumor-infiltrating lymphocytes (TILs) are uncommon in atypical Spitz tumors.•TILs immunophenotype correlates with risk of tumor progression.•A cytotoxic profile and a lower number of B cells characterize benign and low-risk tumors.•PD-L1 expression only correlates with immunoregulatory markers FOXP3 and PD1.•This study expands knowledge of biological behavior of atypical Spitz tumors.
Calciphylaxis is not uniquely observed in uraemic patients, as some cases have also been reported in patients with normal renal function or moderate chronic kidney disease (CKD), in association with ...severe vasculopathy or systemic inflammation. A particular subset worthy of studying is represented by those patients who develop calciphylaxis after kidney transplantation (KT).
Analysis of the local series of calciphylaxis after KT (
= 14) along with all the other cases reported in the literature from 1969 to 2019 (
= 31), for a total population of 45 patients, is presented. Demographic data, CKD history, risk factors, immunosuppression, clinical presentation and management have been analysed both as a whole and according to the time period (before or after the year 2000).
Calciphylaxis developed during the first year after KT in 43.2% of patients and median (interquartile range) creatinine at diagnosis was 2.4 (1.25-4.64) mg/dL. The most frequent presentation included distal purpura or ulcers in one-third of cases and 39.1% of patients were receiving vitamin K antagonists. PTH values were above 500 pg/mL and below 100 pg/mL in 50.0% and 25.0% of cases, respectively. Whole population mortality was 55.6%. As expected, clinical presentation, immunosuppression and management varied depending on the time period. Patients diagnosed after 2000 were older, with longer dialysis vintage, and treatment was usually multimodal; on the contrary, in patients diagnosed before 2000, parathyroidectomy was the treatment of choice in 61.9% of cases.
Calciphylaxis can still occur after KT, in many cases during the first year and in patients with a good renal function. Risk factors and management varied according to the time period studied.
To study the main clinico-biological characteristics and the outcome of patients with diffuse large B-cell lymphoma (DLBCL) according to the primary site (nodal vs. extranodal), we included 262 ...patients consecutively diagnosed with DLBCL in a single institution, 5 years before and after immunochemotherapy was considered as the standard treatment. Altogether 116 patients received CHOP (cyclophosphamide, adriamycin, vincristine, and prednisone) and 146 rituximab plus CHOP (R-CHOP). The primary site was the lymph node in 140 patients (53%), Waldeyer's ring (WR) in 22, gastrointestinal (GI) in 33, and other extranodal in 67. The addition of rituximab significantly improved the CR rate in nodal, but not in extranodal, lymphomas. Patients receiving R-CHOP showed higher OS than those treated with CHOP alone (5-year OS: 71% vs. 48%). This difference was maintained in primary nodal (5-year OS: 69% vs. 37%, p < 0.0001), but was not observed in primary extranodal (75% vs. 65%, p = 0.45) lymphomas. The IPI, treatment, and primary site were the main variables for OS in multivariate analysis. In nodal cases, IPI and treatment maintained value, whereas only IPI predicted OS in extranodal cases. In conclusion, immunochemotherapy treatment dramatically improved the outcome of patients with nodal DLBCL; however, its effect was less in primary extranodal cases, so the prognosis of patients with nodal and extranodal lymphomas has been equalized in the rituximab era.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
γδ T cells represent a minor T-cell subset that is mainly distributed in mucosal surfaces. Two distinct lymphomas derived from these cells have been recognized: hepatosplenic γδ T-cell lymphoma ...(HSTL) and primary cutaneous γδ T-cell lymphoma (PCGD-TCL). However, whether other anatomic sites may also be involved and whether they represent a spectrum of the same disease are not well studied. The lack of T-cell receptor (TCR)β expression has been used to infer a γδ origin when other methods are not available. We studied 35 T-cell tumors suspected to be γδ TCL using monoclonal antibodies reactive with TCR δ or γ in paraffin sections. We were able to confirm γδ chain expression in 22 of 35 cases. We identified 8 PCGD-TCLs, 6 HSTLs, and 8 γδ TCLs without hepatosplenic or cutaneous involvement involving mainly extranodal sites. Two such cases were classified as enteropathy-associated T-cell lymphoma, type II. The other γδ TCL presented in the intestine, lung, tongue, orbit, and lymph node. In addition, we observed 13 cases with mainly extranodal involvement that lacked any TCR expression ("TCR silent"). In all cases, a natural killer cell origin was excluded. In conclusion, the lack of TCRβ expression does not always predict γδ-T-cell derivation, as TCR silent cases may be found. The recognition of γδ TCL presenting in extranodal sites other than skin and liver/spleen expands the clinical spectrum of these tumors. However, non-HSTL γδ TCL do not seem to represent a single entity. The relationship of these tumors with either HSTL or PCGD-TCL requires further study.
Squamoid eccrine ductal carcinoma is a poorly documented skin adnexal carcinoma showing squamous and duct differentiation. It is regarded to be of low-grade malignant potential, but limited follow-up ...information is available. To study their clinical behavior and histologic features, 30 squamoid eccrine ductal carcinomas were identified from departmental and referral files. Hematoxylin and eosin–stained sections were reviewed, and immunohistochemistry for carcinoembryonic antigen and epithelial membrane antigen was examined to confirm duct differentiation. Clinical follow-up was obtained from patient records and referring pathologists. The tumors presented as nodules or plaques (median size, 1.0 cm; range, 0.5 to 2.5 cm) with a predilection for the head and neck (77%). The patients were elderly (median age, 79.5 y; range, 10 to 96 y) with a male predominance. Histologically, these poorly demarcated tumors were characterized by an infiltrative growth pattern within the dermis and additional invasion of subcutis in 70%. Median tumor thickness was 4.3 mm (range, 1.5 to 18 mm). Superficially, the tumors resembled well-differentiated squamous cell carcinoma. In the deeper reaches, they were organized in cords and strands showing duct differentiation in a desmoplastic stroma. Cytologic atypia was moderate to severe. Ulceration (47%), necrosis (23%), and perineural and lymphovascular infiltration (27% and 6%, respectively) were additional features. Follow-up data (median, 29 mo; range, 7 to 99), available for 24 patients (80%), revealed a local recurrence rate of 25%. Three patients had lymph node metastasis, and 1 patient died of metastatic disease. Our study outlines the histologic characteristics of squamoid eccrine carcinoma and emphasizes its clinical behavior with risk for local recurrence and potential for more aggressive behavior with metastasis and rare disease-related mortality.
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