CAR T-cell therapy has become a highly effective treatment for hematological malignancies, and emerging evidence indicates promising benefits for non-oncohematological conditions. As its clinical use broadens, understanding long-term outcomes and late complications is crucial. One critical yet understudied area is fertility, for which current evidence remains limited and no formal guidelines provide direction for patients undergoing CAR T-cell therapy. To address this gap, we conducted a cross-sectional survey on behalf of the Cellular Therapy and Immunobiology Working Party (CTIWP) of the European Society for Blood and Marrow Transplantation (EBMT) focusing on current practices, existing challenges, and reported reproductive outcomes. Questionnaires were distributed electronically (via SurveyMonkey) between Jan 8, 2025 and April 18, 2025 to 247 EBMT-affiliated centers assessing current fertility-related practices and procedures around CAR T-cell therapy. A second, complementary questionnaire was circulated between Dec 23, 2025 and April 9, 2026 to gather detailed information on reported pregnancies following CAR T treatment. 99 of 247 (40%) centers answered and were included in the analysis. At data censoring, 24 pregnancies were reported in 19 patients, resulting in 18 live births, 2 ongoing pregnancy (one with twins), and 4 miscarriages. Eighteen pregnancies occurred in female CAR T-cell recipients, and six were reported by male recipients through their partners. In patients achieving pregnancy, B cell lymphoma was the most common indication for treatment. Pregnancies in the female cohort occurred naturally in 83% of cases (15/18). Among patients with data, the median time between CAR T-cell infusion and delivery or miscarriage was 3 years (range 4 months-6 years). Although both low- and high-grade Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) were reported among these patients, these events did not appear to influence pregnancy outcomes, acknowledging the small sample size. While most centers (52/63, 83%) reported offering fertility counselling before CAR T-cell infusion, 11 centers (17%) indicated that they do not routinely inform patients of the potential reproductive risks. Most centers (79%) offered fertility preservation procedures to male and female patients. The most common barriers to fertility preservation referral were the urgency of initiating bridging therapy to CAR T-cell infusions due to active or rapidly progressive disease in aggressive disease and extensive prior chemotherapy exposure, defined as more than three previous treatment lines. For female patients, the predominant approaches were oocyte cryopreservation (63%) and ovarian tissue cryopreservation (59%). Among male patients, semen collection and cryopreservation was the most frequently used method (93%). Endocrinologic follow-up practices after CAR T-cell therapy varied substantially across centers. We report the largest series of pregnancies and live births after CAR T in patients with hematological malignancies and autoimmune diseases, and the first within Europe. As CAR T-cell therapy is increasingly administered earlier in the treatment algorithms and to younger populations, integrating standardized fertility counselling and preservation strategies into routine care will be essential. The reproductive success highlights the urgent need for robust research and formalized guidelines in this evolving field. None.
Cardiac involvement by cutaneous T-cell lymphoma is exceedingly rare and poses considerable diagnostic and therapeutic challenges. Immune checkpoint inhibitors targeting programmed cell death-1 have reported variable activity in T-cell lymphomas and have been associated with paradoxical progression in select cases. We report a 72-year-old man with longstanding indolent CD8-positive cutaneous T-cell lymphoma and metastatic renal cell carcinoma who developed myocardial infiltration by lymphoma after prolonged nivolumab therapy. Diagnosis was established by surgical cardiac biopsy reporting CD3-positive, CD8-positive, and CD30-negative T-cell lymphoma with clonal overlap with prior cutaneous disease. Given concern for paradoxical progression, therapy was transitioned to avelumab, an antiprogrammed death ligand-1 antibody. After nivolumab discontinuation and transition to avelumab, the patient experienced complete metabolic resolution of cardiac involvement, improvement in cardiac biomarkers, and durable control of cutaneous lymphoma over more than 3 years of follow-up. This case highlights a temporal association between programmed cell death-1 blockade and atypical dissemination of cutaneous T-cell lymphoma, supported by biologic plausibility, and underscores a potential therapeutic distinction between programmed cell death-1 and programmed death ligand-1 inhibition in malignant T-cell disorders.
Defective B cell development underlies a large proportion of inborn errors of immunity. Progress in understanding disease mechanisms and therapy development remains limited because current human in vitro models incompletely recapitulate B-lymphopoiesis. We present a three-dimensional aggregate culture platform composed of human hematopoietic stem and progenitor cells (HSPCs) and mouse bone marrow (BM) stromal cells as an assay for efficient B cell output (ABO). ABOs support progression through pro-B, pre-B, immature, and transitional B cell stages, with a transcriptional profile and B cell receptor (BCR) repertoire diversity resembling human B cell ontogeny. ABO-derived B cells exhibit functional BCR signaling and differentiate into class-switched memory B cells and antibody-secreting cells following CD40-mediated stimulation. ABOs reproduce the B cell developmental arrest observed in HSPCs from patients with RAG1-deficient severe combined immunodeficiency (SCID), which is corrected by a RAG1 gene therapy lentiviral vector. Thus, ABOs provide a clinically relevant platform for modeling B cell immunodeficiencies and evaluating therapeutic strategies.
Diffuse pleural mesothelioma (DPM) is a lethal malignancy with no approved therapies directly targeting tumor cells. Based on reports that epidermal growth factor receptor (EGFR) and MET proto-oncogene (MET) are frequently expressed in DPM, we sought to systematically assess their co-expression and determine the preclinical activity of amivantamab, a bispecific antibody that targets EGFR and MET. We evaluated EGFR and MET expression in patient cohorts and cell lines using transcriptomic analysis, immunohistochemistry, and biochemical assays. The mechanistic actions of amivantamab, including receptor internalization, signaling blockade, and immune-mediated cytotoxicity, were assessed using in vitro co-culture systems with peripheral blood mononuclear cells (PBMCs) and natural killer (NK) cells. In vivo efficacy was evaluated in mesothelioma patient-derived xenograft (PDX) models using immunodeficient mice reconstituted with human NK cells. Transcriptomic and single-cell RNA sequencing analyses of DPM patient cohorts revealed frequent co-expression of EGFR and MET, predominantly in malignant cells. Immunohistochemical analyses confirmed EGFR and MET protein expression across mesothelioma histologic subtypes. In vitro, amivantamab preferentially bound to DPM cells, inhibited ligand-induced EGFR and MET signaling, and promoted receptor internalization. Co-culture experiments demonstrated that amivantamab induced dose-dependent cytotoxicity via NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC). In multiple mesothelioma PDX models, the combination of amivantamab and NK cells significantly reduced tumor growth without overt toxicity. Amivantamab demonstrates robust preclinical antitumor activity in mesothelioma primarily through innate immune-mediated cytotoxicity associated with EGFR and MET engagement. These findings support the clinical evaluation of bispecific EGFR/MET-targeting antibodies in mesothelioma.
Cervical squamous cell carcinoma has been proven to be associated with human papillomavirus(HPV) infection, while the etiology of fallopian tube squamous cell carcinoma remains unclear and there are few literature reports. Clinically, concurrent cases of the two malignancies are even more rare. A female patient presented to our hospital with irregular vaginal bleeding. She underwent hysteroscopic surgery, and the postoperative pathology indicated cervical cancer. She subsequently received laparoscopic surgery, and postoperative pathology unexpectedly confirmed squamous cell carcinoma of the fallopian tube. We speculate that this represents a case of HPV-associated double primary squamous cell carcinomas. At present, the patient's general condition is stable after systematic treatment. This case reminds us to further understand the relationship between HPV infection and gynecological malignancies, as well as the benefits of rational application of opportunistic salpingectomy (OS), and we should strive for early diagnosis and treatment of tumors.
Multimodal profiling of circulating tumor cells (CTCs) and non-tumor circulating cells was performed in six patients with advanced colorectal cancer to identify biological programs beyond enumeration-based analyses. Across all patients, we identified 3,981 CTCs characterized by pronounced EpCAM/L1CAM co-expression, variable PD-L1 expression, and low LGR5 expression, consistent with metastatic-associated phenotypes. Integrated single-cell multi-omics analysis of 1,720 cells revealed genomic instability within EpCAM⁺, L1CAM⁺, LGR5⁺, and PD-L1⁺ CTC subsets, including Y-chromosome loss in male patients and marked intra-patient heterogeneity. In parallel, non-CTCs exhibited upregulation of inflammatory and metabolic dysregulation programs. This hypothesis-generating study highlights the relevance of blood-based multimodal single-cell profiling for interrogating tumor-host states beyond insights from CTC enumeration alone.
Anaplastic large cell lymphoma (ALCL) is a CD30-positive mature T-cell lymphoma. ALK-negative systemic ALCL typically affects older adults, with aggressive clinical behavior. Predominant gastrointestinal involvement is rare and may present with nonspecific systemic symptoms, posing diagnostic challenges, particularly when manifesting as fever of unknown origin. We report a case of a patient with ALK-negative systemic ALCL and predominant gastrointestinal involvement. The patient had a history of indolent cutaneous extranodal marginal zone B-cell lymphoma. The patient presented with a prolonged, intermittent fever and constitutional symptoms. The initial evaluations, including computed tomography, 18F-fluorodeoxyglucose positron emission tomography/computed tomography, and bone marrow examination, were not diagnostic. The persistent fever, which was accompanied by newly developed gastrointestinal symptoms and progressive hypoalbuminemia, prompted an endoscopic evaluation that revealed multiple ulcerofungating gastric lesions. Histopathological examination demonstrated the diffuse proliferation of large atypical lymphoid cells with high CD30 expression, no ALK expression, a high Ki-67 proliferation index, and clonal T-cell receptor gene rearrangement. These findings were consistent with ALK-negative systemic ALCL. Staging then revealed multifocal gastrointestinal involvement. The patient was treated with brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone, following which the febrile episodes improved. This case illustrates an uncommon gastrointestinal-predominant presentation of ALK-negative systemic ALCL presenting as fever of unknown origin. This case underscores the importance of continued diagnostic reassessment and symptom-guided tissue acquisition when conventional staging studies are not initially diagnostic, particularly in patients with a history of indolent lymphoma.
In the era of chimeric antigen receptor (CAR) T-cell therapy, autologous stem cell transplant (ASCT) for diffuse large B-cell lymphoma (DLBCL) is preferentially offered to patients with late relapse (>12 months) who achieve complete or partial response (CR or PR, respectively) to salvage therapy. We conducted a retrospective cohort study using publicly available data from the Center for International Blood and Marrow Transplant Research in this population. We included adult patients with DLBCL, not otherwise specified, and high-grade large B-cell lymphomas who experienced disease relapsed after remaining on a response to first line of treatment for at least 12 months and who achieved a CR or PR after salvage treatment at the time of relapse. A total of 182 patients treated between 2013 and 2021 were included in the analysis: 100 had CR and 82 had PR before ASCT. Median follow-up after ASCT was 34 months (range, 1-95). Overall survival (OS) at 3 years was 67.6%, and progression-free survival (PFS) was 50.6%. Cumulative incidence of relapse at 3 years was 43.9%. Older age (hazard ratio [HR], 1.03; P = .026) and a higher number of previous lines of treatment (HR, 1.43; P = .002) were associated with inferior OS. Multivariable analysis showed that the number of previous treatments had a significant impact on the OS (P = .009), whereas undergoing ASCT in a PR status was the only factor significantly associated with inferior PFS (P = .029; HR, 1.41; 95% confidence interval, 1.09-1.82). In summary, ASCT still provides high efficacy in patients experiencing late relapses (after 12 months) who have chemotherapy-sensitive disease after pretransplant salvage.
Brexucabtagene autoleucel (brexu-cel) is an autologous CD19-directed CAR T-cell therapy approved for relapsed/refractory (R/R) mantle cell lymphoma (MCL) based on the pilot study ZUMA-2. Since then, several US and European real-world studies have demonstrated comparable efficacy outcomes. However, these reports have also suggested potentially higher rates of acute toxicities, particularly immune effector cell-associated neurotoxicity syndrome (ICANS), raising concerns regarding its use, especially in vulnerable populations. At Singapore General Hospital, five patients (median age 75 years) received brexu-cel from April 2025 to Dec 2025 for R/R MCL. Historical cohort MCL patients received allogeneic haematopoietic stem cell transplantation (allo-HSCT) were extracted and compared. For brexu-cel cohort, the overall response rate (ORR) was 100%, with a complete response rate (CRR) of 80%. Cytokine release syndrome (CRS) occurred in 80% of patients, with no grade 3 events, and only one patient developed grade 1 ICANS (20%). These efficacy and safety outcomes compare favourably with historical cohorts of patients who underwent allo-HSCT locally (total 6 patients, 2 relapsed, 2 NRM), despite potentially higher-risk features and less controlled disease at baseline. Efficacy and toxicity of both clinical trial and real-world CAR-T studies for R/R MCL were summarized. To our knowledge, this represents the first real-world report from Asia on brexu-cel in R/R MCL, supporting its use in this region, where published data have thus far predominantly originated from the United States and Europe.
We report a case of a woman in her 60s who initially presented with typical symptoms of multiple myeloma, including fatigue, muscle cramps, lower back pain, hypercalcaemia, renal impairment and anaemia. Laboratory testing revealed elevated free light chains and M protein bands. Treatment was initiated for a working diagnosis of multiple myeloma. However, bone marrow assessment did not find plasma cells, instead revealing that the malignant clonal cells were of B-cell origin. Treatment was subsequently changed to a chemotherapy regimen for diffuse large B-cell lymphoma. After a suboptimal response, the patient received further treatment with a new regimen, resulting in a good response with no signs of active disease. Over 1 year after completing treatment, the patient remains well.
The toxic effects of air pollutants on the airway epithelium are associated with oxidative stress, a pro-inflammatory response, and impaired innate immune responses. The chronic exposure to noxious factors leads to cumulative damage to the alveolar compartment, reduced diffusion capacity, and impaired lung function. This study aimed to investigate the biological responses of bronchial epithelial cells exposed to PM2.5 and microplastic, following prior induction of acute, chronic, and allergic epithelial injury. Primary, normal bronchial epithelial cells were cultivated in air-liquid interface (ALI) in models of normal, acute (lipopolysaccharide (LPS) treated), chronic (cigarette smoke extract (CSE) treated for 14 days), and allergic (house dust mite (HDM)+IL-13 treated for 3 days). Simultaneously, cells were divided into two groups: uninjured or physically injured by a scratch. Cells were then stimulated with microplastic fibres (200 μg/cm2) and PM2.5 (50 μg per insert) applied to the top of the epithelial cell layer for 48 hours. Combined exposure to PM2.5 and microplastics induced profound cytotoxic effects across all models. Mechanical injury modulated inflammatory responses in a model-dependent manner, with the most pronounced dysregulation observed in allergically primed epithelial cells. In control and LPS-stimulated cultures, co-exposure to PM2.5 and microplastics significantly disrupted epithelial barrier integrity. PM2.5 and microplastic exposure were associated with increased TGF-β and EGFR expression across several injury models, with a tendency toward enhanced TGF-β signalling in secretory epithelial cells under chronic and allergic conditions, largely independent of mechanical injury. Overall, pollutant-induced responses varied according to the underlying epithelial injury state. Atmospheric pollutants influenced epithelial immune response, contributing to airway epithelial injury and affecting regenerative capacity, particularly when cellular biology was additionally compromised by bacterial, tobacco or allergic stimuli.
Cells at the invasive front of oral squamous cell carcinoma (OSCC) occupy a partial epithelial-to-mesenchymal transition (p-EMT) state that drives invasion and therapeutic resistance yet remains poorly understood. To define the regulators of this metastable state, we developed an isogenic OSCC model that captures stable epithelial and p-EMT phenotypes and used it to perform a genome-wide CRISPR invasion screen. This unbiased strategy identified 17 modulators of invasion, most previously unrecognized in cancer and virtually unexplored in OSCC, that converge on cytoskeletal remodeling, adhesion, and epigenetic regulation. Within this network, EDIL3 emerged as a central driver of EMT, invasion, and chemoresistance in head and neck cancer, extending prior reports in other tumor types. Importantly, the invasion signature derived from our screen localized with striking specificity to the tumor invasive front of human OSCC, providing direct clinical validation. Together, these findings reveal a novel, targetable network of transient invasion drivers defining the OSCC tumor front.
Granulosa cell tumour (GCT) is the most common primary ovarian neoplasm in cats and may arise from residual ovarian tissue following incomplete spay procedures. To describe the surgical management of a GCT identified in the setting of Ovarian Remnant Syndrome (ORS) in a spayed cat with hyperestrogenaemia without estrus signs, and to assess the potential utility of serum estradiol as an adjunct for diagnosis and postoperative monitoring. A 6-year-old female domestic shorthair cat, reportedly spayed, presented with a 2-week history of weight gain and abdominal distension. Diagnostic imaging and cytology suggested a large neuroendocrine tumour occupying the abdominal cavity. Exploratory laparotomy was performed, and the abdominal mass along with one hepatic nodule was resected. Histopathology confirmed GCT in the abdominal mass with hepatic metastasis. A preoperative serum sample collected at initial presentation and assayed after receipt of the histopathology report showed markedly increased estradiol. Although clinical signs improved after surgery, the cat re-presented 4 weeks later with abdominal distension and severe anaemia; imaging revealed progression of hepatic lesions, and the patient died 5 weeks after surgery. This case highlights that GCT can occur in the setting of ORS without estrus signs, despite marked hyperestrogenaemia. Ovarian remnants may undergo neoplastic transformation and cause life-threatening disease, even in the absence of estrus signs. Serum estradiol may be a valuable marker for diagnosis, treatment response, and recurrence monitoring in feline GCT.
The International Prognostic Index (IPI) is an essential prognostic tool for patients with large B-cell lymphoma (LBCL). To compare outcomes after chimeric antigen receptor T-cell (CART) therapy and allogeneic stem cell transplantation (alloSCT) in relation to IPI risk factors, we analyzed 515 LBCL patients receiving CART (n = 303) or alloSCT (n = 212) as ≥third-line treatment, registered with EBMT (2016-2021). Patients treated with CART were older (median 62.4 vs 51.1 years), had higher IPI scores (48.2% vs 20.8% high/high-intermediate risk), and a higher incidence of refractory disease (84.1% vs 34.6%). At 24 months, overall survival (OS) was 49% vs 41%, progression-free survival (PFS) was 37% vs 32%, relapse-incidence (RI) was 56% vs 38%, and non-relapse-mortality (NRM) was 7% vs 30%, respectively. In multivariate analysis, CART therapy showed superior OS primarily due to significantly lower NRM, while RI was higher. The survival benefit of CART was significant in patients with low/low-intermediate IPI (OS HR 0.43, 95% CI 0.31-0.60), but not observed in high-risk patients. Elevated LDH eliminated the PFS advantage of CART over alloSCT. Poor outcomes after CART in patients with high-risk disease support early preparation for alloSCT for eligible patients.
Kaposi Sarcoma (KS), caused by human herpesvirus 8 (HHV-8), may be observed in transplant recipients in the form of immunosuppression-related KS. While it primarily affects the skin, it can also involve internal organs, particularly the gastrointestinal (GI) system. GI involvement is often asymptomatic, but bleeding episodes may occur. Post-transplant anemia (PTA) is a common complication associated with increased mortality and decreased renal function. Early diagnosis and management are crucial. This report discusses 2 cases of KS in kidney transplant recipients presenting with severe anemia. We report 2 cases of immunosuppression-associated KS with severe anemia in kidney transplant recipients. Case 1 involved a 50-year-old male kidney transplant recipient who developed biopsy-confirmed, skin-limited KS without systemic or gastrointestinal involvement, along with severe anemia 2 months post-transplant. The anemia was identified as pure red cell aplasia, likely induced by immunosuppressive therapy. Immunosuppressive regimen was modified by discontinuing mycophenolate mofetil and switching tacrolimus to everolimus, resulting in regression of KS lesions, normalization of hemoglobin levels, and preserved graft function. Case 2, a 47-year-old female with widespread KS involving the skin, gastrointestinal tract, and lymph nodes, was treated with paclitaxel chemotherapy, erythrocyte transfusions, and immunosuppressive adjustment. At 10-month follow-up, her disease stabilized, and hemoglobin levels returned to the normal range. The evaluation of anemia in transplant recipients presents a complex clinical challenge. Immunosuppression-associated KS can occur during both early and late post-transplant periods. KS may contribute directly to anemia through gastrointestinal involvement or coexist as a concurrent condition alongside other underlying etiologies.
Mixed germ cell tumours (GCTs) are a rare pathology, particularly those comprising yolk sac tumour (YST) and mature cystic teratomas. Although one important biomarker for YSTs is alpha-fetoprotein (AFP), which is often characteristically elevated, this may not be the case in a minority of cases. Additionally, AFP is not usually elevated in mixed GCTs, more so in cases involving mature cystic teratoma, even with YST as a component of the tumour, as seen in the index patient who had a normal AFB value of 5 ng/mL (normal: 0-10 ng/mL). Furthermore, in postmenopausal women with stage 1 mixed GCTs, the preferred treatment is non-fertility-sparing surgery without chemotherapy. Despite the generally poor prognosis for GCTs in this demographic, early detection and treatment can lead to favourable outcomes. This report details a case of a 58-year-old woman with a stage 1 mixed GCT who underwent extensive surgery without chemotherapy and has remained tumour-free for 24 months, attributing her good prognosis to the low stage and early intervention, along with the YST component.
Dysphagia is commonly attributed to intrinsic esophageal pathology; however, extrinsic compression from mediastinal processes remains an important and often underrecognized cause. We report the case of a 69-year-old man who presented with acute dysphagia due to food impaction. Esophagogastroduodenoscopy successfully relieved the obstruction but revealed no intrinsic lesion, instead demonstrating extrinsic compression of the upper esophagus. Subsequent cross-sectional imaging identified a large anterior mediastinal mass extending into the left neck, encasing the aortic arch and its branches, and causing significant esophageal deviation and stenosis. Laboratory evaluation was notable for leukocytosis, anemia, elevated inflammatory markers, and an elevated carcinoembryonic antigen level. Initial attempts at tissue diagnosis, including ultrasound-guided axillary lymph node sampling and endobronchial ultrasound-guided transbronchial needle aspiration, were nondiagnostic due to insufficient or nonrepresentative tissue. Given persistent high clinical suspicion, further tissue sampling was pursued, ultimately establishing a diagnosis of squamous cell carcinoma. This case highlights the diagnostic limitations of endoscopy in the evaluation of extraluminal disease, the challenges of tissue acquisition in mediastinal pathology, and the critical importance of persistence following nondiagnostic biopsies. An imaging-driven, multidisciplinary approach is essential for accurate diagnosis and timely management in patients with suspected mediastinal malignancy.
Femoral hernias are relatively uncommon in clinical practice but are of considerable clinical significance because they are associated with a higher risk of strangulation happening. Even rarer is the discovery of the appendix within the hernia sac, a condition known as De Garengeot hernia, and within this already highly unlikely scenario, having a tumor within the hernia is exceedingly rare. Among such cases, Goblet cell carcinoma (GCC) represents an incredibly rare occurrence. We present the case of an 83-year-old man who had undergone transabdominal preperitoneal (TAPP) repair for an incarcerated femoral hernia. During the operation, the incarcerated part was found to be the tip of the appendix, which made it necessary to perform a laparoscopic appendectomy (LA). Subsequent histopathological examination revealed GCC invading the muscularis propria, and given the patient's advanced age, significant comorbidities, and the family's stated preference, a right hemicolectomy was not performed. At the 1-year follow-up, computed tomography (CT) and tumor markers indicated no sign of recurrence. For older individuals with co-existing health conditions and those at the early stage of GCC, a cautious management approach backed by active monitoring might be a sensible option following a thorough evaluation of risks and benefits, and this instance provides a realistic view on dealing with such rare and medically complex scenarios.
Objective: To summarize current evidence on the use of buprenorphine for chronic pain management in individuals with sickle cell disease (SCD) and identify gaps for future research. Data Sources: PubMed, Embase, and Cochrane CENTRAL were systematically searched from database inception through August 2025 using keywords related to buprenorphine, SCD, chronic pain, and analgesia. Searches were limited to human studies published in English. Study Selection: Seven studies were included involving pediatric or adult patients with SCD treated with buprenorphine for chronic pain. Eligible studies reported at least 1 patient-centered outcome, including pain severity, opioid utilization, health care use, or quality of life. Included study designs were case reports, case series, observational studies, and qualitative studies. Abstract-only publications and studies not specific to SCD were excluded. Data Extraction: Two reviewers independently extracted data using the Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews guidelines, with discrepancies resolved by consensus. Data Synthesis: A descriptive synthesis was performed. Most studies evaluated buprenorphine initiation using microinduction strategies. Buprenorphine was generally well tolerated and associated with reduced full opioid agonist use, fewer emergency department visits and hospitalizations, and improvements in functional outcomes and patient-reported autonomy. Study heterogeneity and small sample sizes limited comparative analysis. Conclusions: Available evidence suggests that buprenorphine may be a safe and effective option for chronic pain management in SCD. Larger prospective studies with standardized induction protocols and validated outcome measures are needed to guide clinical practice. Prim Care Companion CNS Disord 2026;28(3):25r04126. Author affiliations are listed at the end of this article.
Gorlin-Goltz syndrome is a rare autosomal dominant disorder characterized by multiple basal cell carcinomas (BCCs), odontogenic keratocysts, and skeletal anomalies. BCCs in this syndrome typically involve photo-exposed areas, whereas predominant flexural and intertriginous involvement remains exceptionally rare. We report the case of a 42-year-old Moroccan man with Fitzpatrick phototype IV who presented with a more than 30-year history of progressively increasing pigmented and erythematous lesions. Clinical examination revealed more than 100 papules, plaques, and nodules involving the face, axillary folds, inguinal folds, and umbilical region. Some inguinal lesions became ulcerated and symptomatic, with pain and bleeding. Dermoscopy showed characteristic features of BCC, including arborizing vessels, blue-gray ovoid nests, and globules, leading to multiple biopsies that confirmed the diagnosis. Histopathological examination identified three distinct subtypes, nodular, adenoid-cystic, and fibroepithelioma of Pinkus, highlighting marked histopathological heterogeneity. A panoramic jaw radiograph demonstrated multiple odontogenic keratocysts, while chest radiography revealed bifid ribs, fulfilling major diagnostic criteria for Gorlin-Goltz syndrome. Genetic testing was not performed because of limited availability. The patient underwent surgical excision of the most symptomatic lesions. Targeted therapy with the Hedgehog pathway inhibitor vismodegib was considered but was not accessible in our setting. This case highlights a rare flexural-predominant phenotype of Gorlin-Goltz syndrome and emphasizes the importance of recognizing atypical non-sun-exposed presentations to avoid diagnostic delay and ensure appropriate multidisciplinary management.