Sweet syndrome following Moderna COVID-19 vaccine: A case report.

With the COVID-19 pandemic, vaccines have been administered all around the world probably more than ever. Even though they are considered safe, with such a huge quantity of doses used, many adverse effects including cutaneous ones were reported. We report here the case of a male adult with a history of monoclonal gammopathy of undetermined significance who presented with an extensive cutaneous eruption of indurated erythematous papules and plaques 2 days after receiving his first dose of Moderna COVID-19 vaccine (mRNA-1273 SARS-CoV-2 vaccine). Histopathology was compatible with a histiocytoid Sweet syndrome and history suggested that the vaccine contributed to the eruption.

Clinical and histological features of fixed drug eruption: a single-centre series of 73 cases with comparison between bullous and non-bullous forms.

The clinical and pathological aspects of fixed drug eruption (FDE) have been described based on a few case series. To compare bullous FDE (BFDE) and non-bullous FDE (NBFDE) and to determine whether BFDE can be histologically distinguished from other dermatoses presenting with an apoptotic pan-epidermolysis. In this retrospective monocentre study (2005-2016), FDE was classified as BFDE or NBFDE and localized (one anatomical site) or generalized (≥ two sites; GBFDE). Clinical data were extracted from charts, and images were reviewed. Skin biopsies were analysed and compared to the clinical presentation. Three dermatopathologists, blinded to the final clinical diagnosis, evaluated a subset of BFDE cases (n = 8) and 25 biopsies of other bullous diseases known to have an epidermal necrolysis (EN)-like pattern. In total, 73 patients were included in the study. Patients with BFDE (n = 58; GBFDE n = 48) were significantly older (p < 0.001). All patients with GBFDE were hospitalized; 25 had a complication (infectious; n = 19), and eight died (median age: 80). Histology revealed spongiotic (6.7%), interface dermatitis (48.3%) and EN-like (66.3%) patterns. The EN-like pattern was more frequent in BFDE than NBFDE (74% vs 27%; p = 0.008). Melanophages (100% vs 66%; p = 0.02) and massive dermal melanosis (40% vs 4%; p = 0.0005) were more prominent in NBFDE than BFDE. BFDE could not be reliably distinguished from other bullous diseases with EN-like patterns. BFDE belongs to the spectrum of skin conditions with an EN pattern, for which the concept of acute syndrome of apoptotic pan-epidermolysis (ASAP) was previously introduced. Clinical-pathological correlation is mandatory for a diagnosis of BFDE.

Sentinel Lymph Node Biopsy in High-Risk Cutaneous Squamous Cell Carcinoma: Analysis of a Large Size Retrospective Series.

BACKGROUND: One of the most important prognostic factors for mortality in cutaneous squamous cell carcinoma (cSCC) is the development of nodal metastasis. There is no consensus regarding which patient with cSCC should be offered sentinel lymph node biopsy (SLNB). OBJECTIVE: This study aimed to establish the rate of positive SLNBs among patients with high-risk cSCCs and to identify which high-risk features are associated with a positive SLNB. METHODS: Five-year retrospective case series in an academic tertiary care center reviewing 93 SLNBs. RESULTS: Of the 93 SLNBs performed, 5 (5.4%) were positive. Three patients (3/5) had neck dissection and one (1/5) had radiation therapy, with no recurrence at the time of last follow-up. A tumor diameter ≥2 cm, a tumor depth >6 mm or below subcutaneous fat, perineural invasion of nerves with a diameter ≥0.1 mm, moderate or poor histological differentiation, lymphovascular invasion, and immunosuppression were associated with a positive SLNB. All tumors with a positive SLNB were classified as T2b according to the Brigham and Women's Hospital (BWH) tumor staging. LIMITATIONS: Retrospective study and absence of a control group. CONCLUSION: Sentinel lymph node biopsy can be considered for BWH T2b and T3 tumors. However, more randomized controlled studies are needed.

Compound blue nevus: a reappraisal of the concept in the genomic era.

We report a series of 21 compound blue nevi, a rare variant in the vast clinical and morphological spectrum of blue melanocytic proliferations. Clinically, they presented in young adults, with a slight female predominance. One-third were located on the dorsum of the foot. Morphologically, all cases displayed large dendritic melanocytes restricted to the deep layers of the epidermis. The compound component was central and evenly distributed. Melanocytic density ranged from scarce isolated cells to a confluent lentiginous architecture. In 12 of the 21 cases, junctional nests of small, bland, weakly pigmented melanocytes were associated. These nests became confluent in the most cellular cases. In all cases, a dermal component was immediately present underneath, mainly of cellular blue nevus-type. All cases were genetically confirmed to harbor either a GNAQ or GNA11 hotspot mutation. This study expands the morphological spectrum of blue nevi that should not be restricted to a strictly intradermal melanocytic proliferation.

Cutaneous sarcoidosis in a melanoma scar: A case report.

Sarcoidosis is an inflammatory multisystemic disease of unknown etiology with multiple presentations of cutaneous lesions. It characteristically infiltrates scars due to several kind of trauma such as surgery, tattoo and even herpes zoster. We present a case of a 65-year-old woman with progressive distal paresthesia and motor weakness. She was referred to our dermatology clinic for a new violaceous nodular plaque within an old melanoma scar on the posterior neck. On positron emission tomography-computed tomography, there were multiple enlarged thoracic lymphadenopathy and a fluorodeoxyglucose-avid cutaneous lesion on the posterior neck, right in the melanoma scar. Cutaneous and nerve biopsies showed non-necrotising granulomas, supporting the diagnosis of systemic sarcoidosis and excluding melanoma recurrence with metastasis. It is the first case of cutaneous sarcoidosis arising within a melanoma scar. Interestingly, patients with melanoma have a higher risk of sarcoidosis.

[Large scale teaching in pathology]. / Pédagogie à grande échelle en ACP.

Medical education is currently facing great changes that affect all medical specialties, including anatomical pathology. Due to rapidly increasing medical knowledge and diagnostic complexity, we are living an era of teaching resources mutualization. We present different tools that allow large numbers of students to access courses, self-evaluations, and competencies assessments. MOOC platforms and e-learning platforms are central to these new online tools, which include the French National Platform of Medical Specialties, dedicated to the teaching of 50,000 medical residents in France. We also discuss "serious games" and the use of images and virtual slides in anatomical pathology teaching. These new modalities can deliver essential knowledge to large student populations, but they must be used in conjunction with adapted teacher-led courses focusing on competencies and professional skills in order to be fully effective.

Melanocytic Myxoid Spindle Cell Tumor With ALK Rearrangement (MMySTAR): Report of 4 Cases of a Nevus Variant With Potential Diagnostic Challenge.

Melanocytic tumors rarely display extensive dermal myxoid deposits except in the myxoid variant of melanoma. We describe in 4 patients the unusual association of morphologic and genetic features. All cases occurred in males and were located on the limbs or proximal girdle area. Age at diagnosis ranged from 8 to 47 years. Size ranged from 6 to 11 mm. Microscopic analysis showed compound, but mainly dermal melanocytic nevi, all presenting a deep dermal expansion with fascicules of amelanotic spindled cells floating in a myxoid background. Cytologic atypia and mitotic activity were low. The superficial portion was either of spitzoid or nevoid cytology with a limited junctional component. In the initial case, the dermal myxoid component was predominant with rare, barely visible, superficial melanocytic nests. This peculiar morphology was responsible for a delayed diagnostic, which required an extensive panel of antibodies ruling out most, potentially myxoid, soft tissue tumors. We later observed the presence of similar, but more limited, dermal morphologic features in 3 other cases. Immunohistochemistry in the deep myxoid areas was melanA, ALK, SOX10, and MiTF. Molecular studies confirmed the ALK rearrangement by an ALK break-apart fluorescence in situ hybridization technique and by RNA sequencing. The latter identified 4 different 5'-fusion partners. Two gene fusions were undescribed: FBXO28(e2)-ALK(e19) and NPAS2(e2)-ALK(e19), and 2 previously described: TPM3(e7)-ALK(e20) and PPFIBP1(e9)-ALK(e19). No relapse or metastatic evolution was seen during follow-up (3 to 24 mo). We denominated this potentially challenging new variant of compound nevus linked to a kinase fusion: Melanocytic Myxoid Spindle Cell Tumor with ALK Rearrangement.

Unclassified sclerosing malignant melanomas with AKAP9-BRAF gene fusion: a report of two cases and review of BRAF fusions in melanocytic tumors.

The current classification of melanocytic tumors includes clinical, pathological, and molecular data. A subset of lesions remains difficult to classify according to these complex multilayer schemes. We report two cases of deeply infiltrating melanomas with a sclerosing background. The first case occurred on the back of a middle-aged man appearing clinically as a dermatofibroma. The architectural and cytological aspects resembled those of a desmoplastic melanoma but the strong expression of both melanA and HMB45, two stainings usually reported as negative in this entity, raised the question of an alternate diagnosis. The second case was a large, slowly growing, perivulvar tumor in a middle-aged woman. The morphology was complex with a central junctional spitzoid pattern associating an epidermal hyperplasia with large nests of large spindled melanocytes. The dermal component was made of deeply invasive strands and nests of nevoid unpigmented melanocytes surrounded by fibrosis; a perineural invasion was present at the periphery of the lesion. In both cases, aCGH found, among many other anomalies, a chromosomal breakpoint at the BRAF locus. RNA sequencing identified in both an AKAP9-BRAF gene fusion. A complementary resection was performed and no relapses have been observed in the respectively 15 and 6 months of follow-up. Both of these melanomas remained unclassified. We further review the variety of melanocytic tumors associated with such BRAF fusions.

Cutaneous Melanocytoma With CRTC1-TRIM11 Fusion: Report of 5 Cases Resembling Clear Cell Sarcoma.

We report 5 cases of primary intradermal nodular unpigmented tumors with a melanocytic immunophenotype associated with a novel CRTC1-TRIM11 fusion. Clinically, the cutaneous nodules were slowly growing in 3 women and 2 men (25 to 82 y old, median, 28 y) with no specific topography. Lesion size ranged from 4 to 12 mm (median, 5 mm). The tumors were strictly located in the dermis with a nodular pattern. The cells were arranged in confluent nests and fascicules. Central fibronecrotic areas were present in 2 cases. Cells were medium to large, sometimes multinucleated, and presented a spindled and epithelioid cytology with prominent nucleoli. Cytonuclear atypia was constant, and mitotic activity in hotspot areas ranged from 1 to 5/mm². Immunohistochemistry found a constant positivity with S100, MiTF, and Sox10, and a heterogenous staining by MelanA or HMB45. NTRK1 was strongly positive in 3 cases. In all cases, RNA sequencing found an invariable CRTC1(e1)-TRIM11(e2) fusion, confirmed by fluorescent in situ hybridization techniques with a TRIM11 break-apart probe. In 4/4 cases, nuclear TRIM11 expression was positive by immunohistochemistry. Fluorescent in situ hybridization techniques showed no rearrangement of NTRK1 or EWSR1, and array-comparative genomic hybridization displayed no alteration (1 case) or only a whole chromosome 7 gain (2 cases) when performed. No relapse or metastatic event was observed during follow-up [3 to 72 months (median, 14 mo)]. Cutaneous clear cell sarcoma was the main differential diagnosis. Overlapping morphologic features previously described in primary dermal melanomas and paraganglioma-like melanocytic tumors were present. The CRTC1-TRIM11 fusion appears to be specific of an unpigmented nodular tumor combining a melanocytic phenotype and low-grade tumor behavior.

Occurrence of BAP1 germline mutations in cutaneous melanocytic tumors with loss of BAP1-expression: A pilot study.

Melanocytic BAP1-associated intradermal tumors (MBAITs) can either be sporadic or associated with a cancer-predisposition syndrome. In this study we explored the clinical status of 136 patients in which at least one MBAIT was found. 49/136 (36%) of them gave their signed consent for an oncogenetic BAP1 blood test. 28/136 patients (20%) diagnosed with an MBAIT had other MBAITs and/or a personal or familial history of BAP1-related cancers that could clinically designate them as potential carriers of a BAP1 germline mutation. 17 of these 28 patients underwent oncogenetic testing. A deleterious mutation of BAP1 was confirmed in 12/17 cases. 4/17 cases were wild-type; all had a single MBAIT and a history of skin melanoma. A variant of unknown significance was found in one case with multiple MBAITs. Among the 12 mutated cases, multiple MBAITs were present in 10/12 cases and were the only clinical sign in 4/12 cases. The remaining 32/49 blood-tested cases with an isolated MBAIT were wild type for BAP1 in 25/32 cases or showed a variant of unknown significance in 7/32 cases. We recommend, following the diagnosis of a MBAIT, performing a BAP1 immunohistochemistry in all other cutaneous melanocytic tumors removed previously or simultaneously and all skin melanomas. This screening could help clinicians prioritize which patients would most benefit from oncogenetic testing.

Telepathology for intraoperative consultations and expert opinions: the experience of the Eastern Québec Telepathology Network.

CONTEXT: The Eastern Québec Telepathology Network was created to provide uniform diagnostic telepathology services in a huge territory with a low population density. OBJECTIVES: To evaluate the diagnostic concordance and turnaround times of intraoperative consultations (IOCs) and the turnaround time of expert opinions by telepathology. DESIGN: For the IOC part of the study, the first 104 IOC diagnoses from a single hospital were compared with those in the final pathology report. The turnaround time of the IOC was calculated from the arrival of the specimen at the pathology laboratory until the time of the call to the surgeon. For the expert opinion part of this study, the first 94 expert opinions from 5 hospitals were reviewed by comparing the time of the initial request until the time of the final report. RESULTS: Of the 104 cases in the IOC study, 8 diagnoses (7.7%) were slightly discrepant because of differences in terminology but remained in the same category of interpretation. Two cases (1.9%) were significantly discordant. Therefore, 102 cases (98.1%) were either concordant or had no clinically significant discrepancies. The average turnaround time for IOCs was 20 minutes (range, 8-43). For the expert opinion part of the study, reports were signed out within 24 hours in 64 cases (68%) and within 72 hours in 80 cases (85.1%). CONCLUSIONS: The Eastern Québec Telepathology Network allows a rapid, high-quality IOC service to be maintained for a hospital where no pathologist was available on site. It also provides a fast, expert opinion service to pathologists working alone.

Online teaching of inflammatory skin pathology by a French-speaking International University Network.

INTRODUCTION: Developments in technology, web-based teaching and whole slide imaging have broadened the teaching horizon in anatomic pathology. Creating online learning material including many types of media such as radiologic images, whole slides, videos, clinical and macroscopic photographs, is now accessible to most universities. Unfortunately, a major limiting factor to maintain and update the learning material is the amount of resources needed. In this perspective, a French-national university network was initiated in 2011 to build joint online teaching modules consisting of clinical cases and tests. The network has since expanded internationally to Québec, Switzerland and Ivory Coast. METHOD: One of the first steps of the project was to build a learning module on inflammatory skin pathology for interns and residents in pathology and dermatology. A pathology resident from Québec spent 6 weeks in France and Switzerland to develop the contents and build the module on an e-learning Moodle platform under the supervision of two dermatopathologists. The learning module contains text, interactive clinical cases, tests with feedback, virtual slides, images and clinical photographs. For that module, the virtual slides are decentralized in 2 universities (Bordeaux and Paris 7). Each university is responsible of its own slide scanning, image storage and online display with virtual slide viewers. RESULTS: The module on inflammatory skin pathology includes more than 50 web pages with French original content, tests and clinical cases, links to over 45 virtual images and more than 50 microscopic and clinical photographs. The whole learning module is being revised by four dermatopathologists and two senior pathologists. It will be accessible to interns and residents in the spring of 2014. The experience and knowledge gained from that work will be transferred to the next international resident whose work will be aimed at creating lung and breast pathology learning modules. CONCLUSION: The challenges of sustaining a project of this scope are numerous. The technical aspect of whole-slide imaging and storage needs to be developed by each university or group. The content needs to be regularly updated and its accuracy reviewed by experts in each individual domain. The learning modules also need to be promoted within the academic community to ensure maximal benefit for trainees. A collateral benefit of the project was the establishment of international partnerships between French-speaking universities and pathologists with the common goal of promoting pathology education through the use of multi-media technology including whole slide imaging.

The Eastern Québec Telepathology Network: a three-year experience of clinical diagnostic services.

BACKGROUND: The Eastern Quebec Telepathology Network (called Réseau de Télépathologie de l'Est du Québec in French) was created to provide uniform diagnostic telepathology services in a huge territory with low population density. We report our first 3-year experience. METHODS: The network was funded equally by the Québec ministry of Health and Canada Health Infoway, a federal telehealth funding agency. The coverage includes intraoperative consultations (IOC), expert opinions, urgent analyses and supervision of macroscopic description. The deployment of the equipment and software started in 2010 and clinical activities began in January 2011. This network comprises 24 hospitals providing oncologic surgery, of which 7 have no pathology laboratory and 4 have a pathology laboratory but no pathologist. The real-time gross evaluation during IOC was performed using a macroscopy station and the sample selection was performed distantly by a technician, a pathology assistant or the surgeon under on-site pathologist supervision. Slides were scanned into whole-slide images (WSI). RESULTS: As per March 2014, 7,440 slides had been scanned for primary/urgent diagnosis; 1,329 for IOC cases and 2,308 for expert opinions. A 98% concordance rate was found for IOC compared to paraffin material and the average turnaround time was 20 minutes. Expert opinion reports were signed out within 24 hours in 68% of cases and within 72 hours in 85%. A recent multi-method evaluation study of the Network demonstrated that, thanks to telepathology: 1. interruption of IOC service was prevented in hospitals with no pathologist on site; 2. two-stage surgeries and patients transfers were prevented according to surgeons and pathologists; 3. retention and recruitment of surgeons in remote hospitals were facilitated; and 4. professional isolation among pathologists working alone was reduced. This study also demonstrated that wider adoption of telepathology would require technological improvement and that the sustainability of the network requires better coordination and the development of a supra-regional pathology organisation. CONCLUSION: The Eastern Quebec Telepathology Network allowed the maintenance of rapid and high quality pathology services in more than 20 sites disseminated on a huge territory. A second phase is underway to expand telepathology to other regions across the province.

In vitro reconstruction of an autologous, watertight, and resistant vesical equivalent.

PURPOSE: Currently, bladder repair is performed using gastrointestinal segments; however, this technique has a high morbidity rate, and new alternatives are thus needed. The lack of native or synthetic tissue with similar properties of the bladder led us to develop autologous vesical substitutes entirely made by tissue engineering and without exogenous matrices. Watertight function and mechanical resistance are fundamental for the model. The aim of this study was to determine the structural and functional characteristics of our vesical equivalent (VE). MATERIALS AND METHODS: Porcine VEs are produced in 55 days. The cellular types that make up the vesical wall are extracted and purified simultaneously from a small porcine bladder biopsy. Dermal fibroblasts are extracted and cultured in vitro to form cellular sheets. Endothelial cells were seeded on the fibroblast sheets before their superimposition. Urothelial cells are then seeded onto this cellular construction. VEs are characterized by histology, immunostaining, electron microscopy, and cell viability. Mechanical properties of the reconstructed substitutes are evaluated by uniaxial tensile tests, and tissue absorption is verified with (14)C-urea, which quantifies the degree of impermeability. RESULTS: This process allowed us to obtain a highly structured tissue with a total fusion of the fibroblast layers. As expected, histological observations showed a pseudostratification of the urothelium developing on an organized self-secreted extracellular matrix. Positive markers for cytokeratin 8/18 in immunostaining confirmed the presence of a urinary epithelium. Electron microscopy confirmed the normal aspect of urothelial cells. Our VE's permeability to (14)C-urea was significantly similar to porcine bladder, and characterization of the mechanical properties indicated that our tissue could be suitable for grafting since its ultimate tensile strength compares favorably with a native porcine bladder. CONCLUSION: The construction of a VE using this method seems very promising in meeting the needs in the urological field. Our substitute has proven its efficiency as a barrier to urea and has a sufficient mechanical resistance to support suturing. Additionally, this model is completely autologous, and its possible endothelialization could promote the early vascularization process after grafting and thus significantly reducing inflammation and possible rejection.