Cutaneous localization of angioimmunoblastic T-cell lymphoma may masquerade as B-cell lymphoma or classical Hodgkin lymphoma: A histologic diagnostic pitfall.

BACKGROUND: We report the cases of three patients presenting skin lesions whose biopsies showed nodular polymorphic infiltrates consisting of lymphocytes, plasma cells, histiocytes, eosinophils, B blasts, and Hodgkin Reed-Sternberg (HRS)-like cells. Two of them were initially diagnosed as classical Hodgkin lymphoma (cHL), on the other hand, the last one as a B-cell lymphoma. All patients have been treated for angioimmunoblastic T-cell lymphoma (AITL). METHODS: We performed a second review of the skin biopsies with further immunophenotypic molecular analyses. Scrupulous observation revealed, in the background of the three cases, atypical small to medium-sized lymphocytes carrying a CD3+, CD4+ T-cell phenotype and expressing PD1 and CXCL13 follicular helper T-cell markers. The two lesions initially diagnosed as cHL showed scattered HRS-like cells with CD30+, CD15+, PAX5+, CD20-, Epstein Barr Virus (EBV) + classical phenotype. The case initially diagnosed as B-cell lymphoma showed a diffuse B-cell proliferation associated with small B-cell and medium to large-sized B blasts that were positive for EBV. CONCLUSION: Those cases highlighted that atypical T-cells may be obscured by B-cell proliferation mimicking cHL or B-cell lymphoma in cutaneous localization of AITL and confirmed the requirement of collecting clinical information before performing a diagnosis.

Diagnostic value of STMN1, LMO2, HGAL, AID expression and 1p36 chromosomal abnormalities in primary cutaneous B cell lymphomas.

AIMS: Distinction between primary cutaneous follicular lymphoma (PCFL) and primary cutaneous marginal zone lymphoma (PCMZL) is challenging, as clear-cut immunophenotypical and cytogenetic criteria to segregate both entities are lacking. METHODS AND RESULTS: To characterize PCFL and PCMZL more clearly and to define criteria helpful for the differential diagnosis, we compared expression of immunohistochemical markers [LIM-only transcription factor 2 (LMO2), human germinal centre-associated lymphoma (HGAL), stathmin 1 (STMN1), activation-induced cytidine deaminase (AID), myeloid cell nuclear differentiation antigen (MNDA)] and the presence of cytogenetic abnormalities described previously in nodal follicular lymphoma [B cell lymphoma 2 (BCL2) and BCL6 breaks, 1p36 chromosomal region deletion (del 1p36)] in a series of 48 cutaneous follicular and marginal zone lymphomas [cutaneous follicular lymphoma (CFL) and cutaneous marginal zone lymphoma (CMZL)]. Immunostaining for STMN1, LMO2, HGAL and AID allowed the distinction between CFL and CMZL, and STMN1 was the most sensitive marker (100% CFL, 0% CMZL). LMO2, HGAL and AID were positive in 93.2%, 82.1% and 86.2% CFL (all CMZL-negative). MNDA was expressed in both entities without significant difference (10.3% CFL, 30.8% CMZL, P = 0.18). BCL2, BCL6 breaks and the del 1p36 were present in 16.7%, 10.7% and 18.5% CFL and no CMZL. Finally, three and 29 CFL were reclassified as secondary cutaneous follicular lymphomas (SCFL) and PCFL without significant differences concerning phenotypical and cytogenetic features. BCL2, BCL6 breaks and the del 1p36 were present in 11.1%, 8% and 16.7% PCFL and did not impact the prognosis. CONCLUSION: LMO2, HGAL, STMN1 and AID, but not MNDA, are discriminant for the recognition between CFL and CMZL. BCL2, BCL6 rearrangements and the del 1p36 have a role in the pathogenesis of PCFL, the latest being the most common alteration.

Impact of expert pathology review in skin adnexal carcinoma diagnosis: Analysis of 2573 patients from the French CARADERM network.

PURPOSE: To prospectively assess the impact of expert pathological review of skin adnexal carcinoma diagnosis in France. METHODS: From 2014 to 2019, 2573 samples from patients with newly diagnosed or suspected skin adnexal carcinomas were reviewed prospectively by expert pathologists through the national CARADERM (CAncers RAres DERMatologiques) network. Changes in diagnosis between referral and expert review were analysed regarding their potential impact on patient care or prognosis. RESULTS: The samples comprised 2205 newly diagnosed adnexal carcinomas, 129 benign adnexal tumours, 136 basal cell carcinomas, 74 squamous cell carcinomas, six cutaneous metastases and 13 other malignancies. There were 930 (42%) sweat gland carcinomas, of which porocarcinoma (261; 11.8%), microcystic adnexal carcinoma (125; 5.7%) and hidradenocarcinoma (109; 4.9%) were the most frequent subtypes; 778 (35%) hair follicle carcinomas, 238 (11%) sebaceous carcinomas and 212 (10%) extramammary Paget diseases/mammary-like anogenital gland adenocarcinomas. A diagnostic change between referral and expert review occurred in 503 (21.3%) patients, significantly higher for cases sent with a provisional diagnosis seeking an expert second opinion (45.7%) than for cases sent with a formal diagnosis (2.8%) (p < .0001). Sweat gland carcinomas were more prone to diagnostic discrepancies than other tumours (p < .0001), including 1.8% of patients with sweat gland carcinoma subtype misclassification with predicted clinical impact. Changes between benign and malignant conditions occurred in 117 samples (5% of patients). CONCLUSION: The study provides a unique description of the distribution of skin adnexal carcinomas and highlights the importance of expert review for these rare cancers. Optimal clinical management was impacted in a significant proportion of patients.

Primary cutaneous neuroendocrine carcinoma within a cystic trichoblastoma: a nonfortuitous association?

Merkel cell (primary cutaneous neuroendocrine) carcinoma is a rare neoplasm of the skin. Its occurrence has been reported in association with other cutaneous neoplasms (Bowen disease, squamous cell carcinoma) in cases regarded as collision tumors. It has recently been described in association with cysts of the follicle apparatus. We present a unique case of rapidly growing nodular tumor on the left forearm of an 84-year-old woman, which proved to be a Merkel cell carcinoma located within a cystic trichoblastoma. The malignant component located in the center of the lesion had typical histopathological and immunohistochemical features of Merkel cell carcinoma. It was surrounded by an epithelial proliferation, made of K17-positive basaloid cells, whose aspects where those of trichoblastoma in a retiform pattern. Both lesions were intertwined, suggesting that the Merkel cell carcinoma had developed within a previously existing trichoblastoma and that it derived from the follicular Merkel cells present in the trichoblastoma. The unique features of this case, together with the reported cases of Merkel cell carcinoma arising within follicular lesions, and the fact that numerous Merkel cells are normally localized in the adult hair follicle, further support the hypothesis of a histogenetic link between normal follicular Merkel cells and Merkel cell carcinoma.

[Constipation in the hospital. Ethical reflection on its care by the nursing staff]. / Elimination intestinale à l'hôpital. Réflexion éthique sur sa prise en charge par les soignants.

The intestinal elimination of the hospitalized patients is a function insufficiently taken into account by the nursing staff from a preventive point of view. Nevertheless, numerous patients present transit disorders which are mostly translated into a diagnosis of constipation requiring therapeutic prescriptions and sometimes even aggressive and expensive medical examinations. The objective of this work is to lead an ethical reflection on the care of intestinal elimination by the nursing staff. Through a questionnaire, we wish to answer 3 questions: how come the nursing staff have difficulties taking care of the intestinal elimination of the hospitalized patients? What are the determiners which influence the care of the intestinal elimination by the nursing staff? Does training prepare the nursing staff to take care of the intestinal elimination of the hospitalized patients? The questionnaire was distributed to doctors, male and female nurses, nursing auxiliaries and students in care of the sick working in medicine, surgery and intensive care of the same hospital. This survey allowed to question 130 persons among whom 36 doctors, 37 male and female nurses, 30 nursing auxiliaries and 27 students. We were able to confirm that the care of the intestinal elimination is insufficiently taken into account in a preventive way, because 56 % of the people interviewed explain that the problem of intestinal elimination is not approached before the complaint of the patient Several determiners make that the nursing staff are not in a preventive approach. This care does not meet much interest, is experienced as devaluing, taboo and the relation nursing staff-patient is hindered because everyone has difficulties to speak about it. Institutional difficulties are also discussed, such as the lack of coordination of the nursing staff and the lack of time. Another point of this survey shows that work experience is not an element which facilitates this care because the more the nursing staff have experience, the more they postpone this care and more the embarrassment is felt Finally, we were able to point out that the received training does not prepare the nursing staff to take care of this function. Indeed, 61% of the people interviewed explain that certain difficulties are inferred by the lack of social skills of the professionals, like the discomfort to speak about this particular need. This work thus allowed to lead this ethical reflection on the care of the intestinal elimination to understand its meaning.As Spinoza said: "One should not laugh, one should not despair, one should not curse, but one should understand".

Novel three-way complex rearrangement of TRPM1-PUM1-LCK in a case of agminated Spitz nevi arising in a giant congenital hyperpigmented macule.

The genetic anomalies associated with the agminated variant of Spitz nevus have so far been limited to HRAS G13R mutations, especially when arising within a nevus spilus. A previous report exposed the case of a man with a giant pigmented macule involving his upper right limb and trunk. Since childhood, Spitz nevi have been periodically arising, within the pigmented area. The histopathology of several lesions displayed the usual criteria of junctional, compound, or intradermal Spitz nevi with a diversity of cytomorphological and architectural features. Some lesions spontaneously regressed. Genetic studies confirmed in three lesions an identical translocation involving TRPM1, PUM1, and LCK. No mutations in HRAS, NRAS, BRAF, or other known fusion genes linked to Spitz nevus were detected. LCK break-apart fluorescence in situ hybridization confirmed the rearrangement was present not only in the melanocytic proliferation but also in the surrounding non-spitzoid melanocytes. This report expands the list of genetic alterations involved both in giant congenital macules and in agminated Spitz nevi, and also extends the concept of mosaicism in melanocytes to gene translocations.

Characterisation of tumour microenvironment and immune checkpoints in primary central nervous system diffuse large B cell lymphomas.

Primary central nervous system diffuse large B cell lymphoma (PCNS-DLBCL) is a rare and aggressive entity of diffuse large B cell lymphoma (DLBCL). Elements of the tumour microenvironment (TME) including tumour-infiltrating lymphocytes (TILs) and tumour-associated macrophages (TAMs) have been associated with survival in DLBCL but their composition and prognostic impact in PCNS-DLBCL are unknown. Programmed cell death-1 (PD1)/programmed death-ligand 1 (PD-L1) immune checkpoint may represent a therapeutic option. Here, we aimed to characterise PD1/PDL1 immune checkpoints and the composition of the TME in PCNS-DLBCL. We collected tumour tissue and clinical data from 57 PCNS-DLBCL and used immunohistochemistry to examine TAMs (CD68, CD163), TILs (CD3, CD4, CD8, PD1) and tumour B cells (PAX5/PDL1 double stains, PDL1). The PDL1 gene was evaluated by fluorescence in situ hybridization (FISH). PAX5/PDL1 identified PDL1 expression by tumour B cells in 10/57 cases (17.5%). PDL1 gene translocation was a recurrent cytogenetic alteration in PNCS-DLBCL (8/47.17%) and was correlated with PDL1 positive expression in tumour B cells. The TME consisted predominantly of CD163 (+) M2 TAMs and CD8 (+) TILs. Most TAMs expressed PDL1 and most TILs expressed PD1. The density of TAMs and TILs did not associate with outcome. We showed that expression of PD1 on TILs and PDL1 on TAMs, but not the expression of PDL1 on tumour B cells was correlated with better prognosis. These findings support a significant role of TME composition and PD1/PDL1 crosstalk in PCNS-DLBCL pathogenesis and bring new insights to the targeted therapy of this aggressive lymphoma.

Systemic, primary cutaneous, and breast implant-associated ALK-negative anaplastic large-cell lymphomas present similar biologic features despite distinct clinical behavior.

Despite distinct clinical presentation and outcome, systemic, primary cutaneous, and breast implant-associated anaplastic large cell lymphomas (S-, PC-, BI-ALCL) ALK-negative (ALK-) show similar histopathological features including the presence of the "hallmark" cells with horseshoe-shaped nuclei and CD30 protein expression. The purpose was to better characterize these three entities using immunohistochemistry and FISH (Fluorescent in situ hybridization) to identify biomarkers differently expressed and that might be involved in their pathogenesis. Twenty-two S-ALCL ALK-, 13 PC-ALCL, and 2 BI-ALCL were included. Cases were tested for P53, P63, MUM1, MYC, GATA3, p-STAT3, PD1, and PDL1 protein expression and DUP22, TP53, TP63, MYC, and PDL1 chromosomal aberrations. As expected, S-ALCL ALK- patients had adverse outcome compare to PC and BI-ALCL. No difference was observed between the three groups concerning protein expression except for MUM1 that was significantly more frequently expressed in S-ALCL ALK- compared to PC-ALCL. In particular, constitutive activation of the STAT3 pathway and PDL1/PD1 immune-checkpoint expression was present in the three entities. TP53 deletion and PDL1 gene amplification were the commonest cytogenetic alterations and were present in the three entities. None of the studied biological parameters was associated with prognosis. Despite distinct clinical behavior, S-ALCL ALK-, PC-ALCL, and BI-ALCL share similar biological features. Larger series should be investigated with the current approach to determine more precisely the activity and the prognostic value of these biomarkers and pathways in each group.

Pseudoepitheliomatous epidermal hyperplasia in tattoos: report of three cases.

Cutaneous reactions to tattoos are not uncommon and various histologic patterns have been reported, including lichenoid, granulomatous, eczematous, and pseudolymphomatous reactions. Such patterns may develop with highly variable delay after the tattooing procedure. We report three strikingly similar cases of a fast-occurring, tattoo-induced, cutaneous reaction strictly restricted to the red parts of the tattoos in two cases and displaying an unusual histologic pattern, i.e. pseudoepitheliomatous hyperplasia. Clinical differential diagnosis of this rare condition includes viral warts, keratoacanthoma, and verrucous carcinoma. It may be difficult to rule out the last two diagnoses and making the diagnosis usually requires full excision of the lesion, comprehensive histologic analysis, and careful follow-up.

Panniculitis due to non-tuberculous mycobacteria in two immunocompromised patients.

Inflammation of subcutaneous tissue (panniculitis) may occur in association with tuberculosis, but so far only three cases of non-tuberculous mycobacteria-related lobular panniculitis have been reported. We describe two new cases with marked cellular immunity failure due to hypercorticism. Clinical presentation did not differ significantly from lobular panniculitis of other aetiologies. Histological samples displayed signs of lobular panniculitis and clues for mycobacteria infection with granulomatous lesions and presence of numerous acid-fast bacilli on special staining. Both patients responded quickly to a combination of macrolides, ethambutol and fluoroquinolones. However, like in other infections with tuberculous or non-tuberculous mycobacteria, long-term treatment (at least 6 months) was necessary to prevent relapses.