Acrokeratosis paraneoplastica (Basex syndrome) with trachyonychia preceding the diagnosis of squamous cell carcinoma of the lung.

Acrokeratosis paraneoplastica (Basex syndrome) is a rare paraneoplastic condition hallmarked by psoriasiform lesion development on acral surfaces, most often related to an underlying squamous cell carcinoma. Patients may also present with nail plate changes. Successful management of this condition can be accomplished by treating the underlying malignancy.

Multicentric reticulohistiocytosis revealing a ductal breast cancer in situ: A case report with dermoscopic and histopathological findings. / Reticulohistiocitosis multicéntrica reveladora de cáncer de mama ductal in situ: reporte de caso con aspectos dermatoscópicos e histopatológicos.

Multicentric reticulohistiocytosis is a rare non-Langerhans cell histiocytosis of unknown etiology. It is classified as multicentric because of multisystem involvement. The disease predominantly affects the skin and joints, but visceral involvement is possible. Multiple erythematous-brownish, pruritic nodules and papules on the face, hands, neck, and trunk are characteristic. It is associated with autoimmune diseases, or malignant neoplasms are seen in 20% to 30% of patients with multicentric reticulohistiocytosis. The diagnosis is based on histopathology of affected tissues. As it is an underreported disease, there is no standardized treatment. A case of multicentric reticulohistiocytosis is reported as a paraneoplastic manifestation of ductal breast cancer, being successfully treated with no recurrence after two years of follow-up. Few cases of multicentric reticulohistiocytosis associated with breast cancer have been reported in the literature.

La reticulohistiocitosis multicéntrica es una enfermedad inflamatoria, una histiocitosis de células no Langerhans, poco frecuente y de etiología desconocida. Se clasifica como multicéntrica al presentar compromiso multisistémico. La enfermedad afecta predominantemente a la piel y las articulaciones, pero es posible la afectación visceral. Las manifestaciones cutáneas se caracterizan por múltiples nódulos y pápulas de color eritemato-marronáceas, pruriginosas en la cara, manos, cuello y tronco. Se asocia a enfermedades autoinmunes y neoplasias malignas, observándose entre el 20 y el 30% de los pacientes con reticulohistiocitosis multicéntrica. Su diagnóstico se realiza sobre la base de la histopatología de tejidos afectados. Al ser una enfermedad poco reportada, no existe tratamiento estandarizado. Se reporta un caso de reticulohistiocitosis multicéntrica como manifestación paraneoplásica a un cáncer ductal de mama, siendo tratadas con éxito, sin recidivas luego de dos años de seguimiento. Pocos casos se han reportado en la literatura de reticulohistiocitosis multicéntrica asociado a cáncer mamario.

Paraneoplastic pemphigus presenting as a prodrome to aggressive T cell lymphoma.

Paraneoplastic pemphigus (PNP) is a rare disease with an unclear mechanism of pathogenesis. We present a case of a male patient who presented with wound management after being diagnosed with Castleman disease-associated paraneoplastic pemphigus (PNP). The patient's condition was not improving; as a result, extensive workup was repeated, which confirmed the diagnosis of aggressive T cell lymphoblastic lymphoma. Our case signifies the importance of keeping a high index of suspicion for PNP-associated malignancies. This case report also adds emphasis to the diagnostic challenges faced by clinicians, making clinical correlation with multidisciplinary approach essential. Therefore, if clinically indicated, we need to revisit the diagnosis and seek alternative explanations to prevent delays in management.

Tumour-induced osteomalacia: the long road to diagnosis and recovery.

Tumour-induced osteomalacia is caused by tumorous production of fibroblast growth factor 23 (FGF23) leading to urinary phosphate wasting, hypophosphataemia and decreased vitamin D activation. The resulting osteomalacia presents with muscle weakness and bone pain but progresses to multiple pathological fractures. Patients often remain undiagnosed for years with severe physical, psychological and economic ramifications. A young woman presented with multiple spontaneous fractures including bilateral femoral fractures. Laboratory tests revealed severe hypophosphataemia, elevated bone turnover markers and low to normal calcium and 25-hydroxy-vitamin D levels. Treatment with phosphate, alfalcalcidol, calcium and magnesium was initiated. 68Gallium-DOTATOC positron emission tomography imaging revealed a mass in the right foot and venous sampling of FGF23 from all extremities confirmed this tumour as the culprit. Biopsy and histology were consistent with a phosphaturic mesenchymal tumour, which was surgically resected. Phosphate levels quickly normalised postoperatively but a long convalescence with hungry bone syndrome, fracture healing and physical therapy followed.

Clinical Features of Cutaneous Paraneoplastic Syndromes in Hodgkin Lymphoma.

Cutaneous paraneoplastic syndromes due to Hodgkin lymphoma present with a wide spectrum of clinical manifestations from generalized pruritus to exfoliative erythroderma. We summarize the clinical findings and outcomes of 14 patients with Hodgkin lymphoma and associated cutaneous paraneoplastic syndromes treated at Mayo Clinic over the past 3 decades. Cutaneous paraneoplastic syndromes may be present at the time of lymphoma diagnosis, whereas in other patients, it may appear at the time of relapse, including patients with initial absence of cutaneous manifestations during the initial lymphoma presentation. Our results indicate that complete resolution of the paraneoplastic syndrome is associated with significantly improved overall survival. Recognition of cutaneous paraneoplastic syndromes is a crucial surrogate of relapsed malignancy and treatment requires targeting the underlying malignancy.

Thymic carcinoma presenting with overlap polyarthritis and myositis: A rare paraneoplastic syndrome in childhood.

Thymic tumors are very rare neoplasms in children and account for less than 1% of mediastinal tumors in pediatric patients. One-third of the pediatric patients present with symptoms related to the compression of the tumor mass on the surrounding anatomic structures, and paraneoplastic syndromes such as myasthenia gravis, pure red cell aplasia, acquired hypogammaglobulinemia, and connective tissue disorders, which rarely occur in children with thymic tumors. Herein, we report a case of thymic carcinoma mimicking the symptoms of a connective tissue disease with symmetrical polyarthritis accompanying myositis, fever, weight loss, and malaise in a 15-year-old male patient. To our knowledge, this is the first case pediatric thymic carcinoma accompany with severe polyarthritis and myopathy, thus we have reviewed the current literature regarding the cases of thymic malignancies coexisting with paraneoplastic syndromes in children.

Digital Gangrene as a Paraneoplastic Manifestation of Peripheral T-cell Lymphoma Not Otherwise Specified Type.

BACKGROUND: Peripheral T cell lymphoma (PTCL), not otherwise specified (NOS) is a heterogenous group of predominantly nodal T cell lymphomas that generally presents with lymphadenopathy with or without extra nodal involvement. Acral vascular syndrome clinically presents as digital ischemia with Raynaud's phenomenon and acral cyanosis. Although, this condition is commonly associated with connective tissue disorder, smoking and vasculitis, its association with lymphoid malignancy is very rare. Here, we present a case report of a patient with digital gangrene of all toes and fingers as a presenting symptom of PTCL-NOS. CASE DESCRIPTION: A 62 year old male presented with digital ischemia associated with pain, low grade fever, loss of appetite and significant weight loss of 6 kilograms over a period of 3 months. On examination, he was found to have bilateral inguinal and axillary lymph nodes with gangrenous changes over toes and fingers but peripheral pulses were palpable. On evaluation he had anemia, elevated ESR and CRP. CT angiogram revealed thinned out digital arteries with multifocal areas of narrowing. Patient was screened for other causes of digital gangrene and was tested negative for ANCA, ANA, cryoglobulins and viral markers. Lymph node biopsy with IHC was suggestive of peripheral T-cell lymphoma-NOS and was started on CHOP regimen. Lymph nodes size decreased and gangrenous changes resolved. CONCLUSION: Though digital ischemia is a rare paraneoplastic presentation of lymphoma, it should be considered if there is a rapid progression of gangrene. Early initiation of chemotherapy may result in the reduction of further progression of digital gangrene and thus prevent permanent disability. In our patient, progression of gangrene was prevented even though it was an aggressive variant of T cell lymphoma.

Membranous Nephropathy as a Paraneoplastic Syndrome in Cancer of Unknown Primary.

BACKGROUND/AIM: Membranous nephropathy (MN) is a nephrotic syndrome with both idiopathic and secondary etiologies. The mechanism of cancer-associated MN is presumed to involve the immunological production of antibodies against a tumor antigen, although little is known about the detailed mechanism. Lung cancer is a major neoplasm associated with cancer-associated MN. However, the simultaneous occurrence of secondary MN in patients with cancer of unknown primary (CUP) remains unclear. CASE REPORT: Here, we present a case of secondary MN in a 72-year-old female as a paraneoplastic syndrome in CUP. Thoracic radiotherapy up to a total of 60 Gy was initially performed on the right subclavian and mediastinal lymph nodes. Computed tomography revealed marked shrinking of these lymph nodes, and the secondary MN also improved without any symptoms. CONCLUSION: The presence of proteinuria in patients with CUP suggests the possibility of secondary MN as a rare differential diagnosis.

[Paraneoplastic subacute cutaneous lupus erythematosus]. / Paraneoplastischer subakut kutaner Lupus erythematodes.

The genesis of subacute cutaneous lupus erythematosus (SCLE) is multifactorial and includes idiopathic, drug-related and paraneoplastic etiologies. This article reports the case of a 70-year-old female patient with paraneoplastic SCLE in whom a lung adenocarcinoma was detected during the extended examination. A paraneoplastic SCLE should be considered when a patient with SCLE presents with lesions in regions of the skin not exposed to sunlight and beginning B symptoms.

A 50-Year-Old Man Presenting with Multiple Bone Lesions and a Diagnosis of Phosphaturic Mesenchymal Tumor of the Femur.

BACKGROUND Phosphaturic mesenchymal tumor (PMT) is an extremely rare mesenchymal neoplasm that is commonly seen in bone and soft tissue. It is associated with a paraneoplastic syndrome, oncogenic osteomalacia, due to tumor-induced urinary phosphate wasting. It is demonstrated to be predominantly mediated by fibroblast growth factor 23 (FGF23)/fibroblast growth factor receptor 1 (FGFR1) axis. Clinically, PMT usually presents as a solitary lesion in the bone. The diagnosis of PMT is challenging due to its non-specific clinical manifestation, radiologic findings, and morphological features. CASE REPORT We report the case of a 50-year-old man presenting with multiple lytic bone lesions and associated pathologic fracture of the right femur, clinically suspicious for multiple myeloma or other metastatic malignant process. Resection from the right femur showed a hypercellular lesion composed of oval-to-spindled cells infiltrating the native trabecular bone with admixed multinucleated giant cells. Immunohistochemical (IHC) staining and in situ hybridization (ISH) demonstrated the tumor cells were positive for SATB2, ERG, FGFR1, and FGF23 ISH. DNA and RNA next-generation sequencing showed marked increases in mRNA levels of FGF23 and FGFR1. The constellation of clinicoradiologic, histomorphologic, IHC, and molecular findings supported a diagnosis of primary benign PMT. CONCLUSIONS This case report discusses a patient with PMT presenting with multifocal lesions due to tumor-induced osteomalacia at initial presentation. We hope that this report will increase the awareness of clinician and pathologists of PMT as a differential diagnosis in patients presenting with multifocal lytic bone lesions. In turn, this will prevent misdiagnosis and overtreatment of a typically benign process.

Updates in the Management of Paraneoplastic Syndrome.

Paraneoplastic neurological syndromes (PNS) are defined as remote neurologic immune-mediated effects triggered by underlying systemic tumors. While recognizing specific syndromes can aid early cancer detection, overutilization of paraneoplastic assays in the absence of a classic syndrome can precipitate overdiagnosis and overtreatment. PNS involve autoantibodies targeting intracellular or extracellular antigens, with variable immunotherapy responses based on antigen type. Diagnosing PNS is challenging, requiring exclusion of other differential diagnoses. New diagnostic criteria classify PNS into high-risk and intermediate-risk phenotypes based on clinical phenotype, neuronal antibodies, and cancer presence. Patients with cell surface antibodies respond better to immunotherapies compared to those with intracellular antigen targets. Understanding PNS syndromes, serological markers, and oncological features guides management, which facilitates initiation of immunosuppression for PNS alongside treatment of the underlying neoplasm, thereby improving neurologic and oncologic outcomes. Initial treatments often include intravenous methylprednisolone, plasma exchange, or intravenous immunoglobulins. Second-line immunosuppressants like rituximab or cyclophosphamide may be necessary if initial treatments fail. Specific therapies vary based on antibody target. Here, we summarize the current approach to the investigation, diagnosis, and treatment of patients with suspected PNS.

Risk factors and prognosis of malignant peritoneal mesothelioma with paraneoplastic syndrome.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare and highly aggressive tumor. Its clinical manifestations are diverse, and the symptoms are not specific. Some patients will develop paraneoplastic syndrome (PS) during the disease course. This study aims to analyze the risk factors of PS in patients with MPM and their impacts on prognosis. METHODS: The clinical data of MPM patients who underwent cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) at our center from June 2015 to May 2023 were retrospectively analyzed. MPM patients were divided into PS group and non-PS group according to the diagnostic criteria. Univariate and multivariate analyses were performed to explore the risk factors of PS in MPM patients, and to analyze the impact of PS on prognosis. RESULTS: There were 146 MPM patients in this study, including 60 patients (41.1%) with PS and 86 patients (58.9%) without PS. The highest incidence of PS was thrombocytosis (33.6%), followed by neoplastic fever (9.6%). Univariate analysis revealed 8 factors (P < 0.05) with statistically significant differences between the two groups: prior surgical scores, targeted therapy history, Karnofsky performance status score, preoperative carbohydrate antigen (CA) 125 level, vascular tumor embolus, peritoneal cancer index, completeness of cytoreduction (CC) score and intraoperative ascites. Multivariate analysis identified 3 independent factors associated with PS: preoperative CA 125 level, vascular tumor embolus, and CC score. Survival analysis demonstrated that MPM patients with PS had worse prognosis, although PS was not an independent prognostic factor. CONCLUSIONS: PS is not rare in patients with MPM, and is independently associated with preoperative CA 125 level, vascular tumor embolus and CC score. PS often indicates advanced disease and poor prognosis.

[Bazex syndrome: a rare paraneoplastic disease]. / Síndrome de Bazex: una enfermedad paraneoplásica infrecuente.

Bazex syndrome is a paraneoplastic disorder most commonly linked to squamous cell carcinomas of the upper aerodigestive tract, followed by lung cancer and other malignancies. It manifests through three stages of skin involvement that mirror the tumor's progression. Remarkably, skin lesions precede tumor symptoms or diagnosis in two-thirds of cases, underscoring the crucial role of suspecting this condition as it can promptly reveal an underlying neoplasm. Treatment primarily focuses on addressing the root neoplasm, with recurrent skin lesions potentially indicating tumor relapse. In this context, we present a clinical case involving a male patient whose manifestation of this syndrome facilitated the timely diagnosis of lung adenocarcinoma. This case underscores the significance of understanding this uncommon syndrome and its link to cancer, enabling early and accurate oncological diagnosis.

El síndrome de Bazex es una enfermedad paraneoplásica que se asocia con mayor frecuencia a carcinomas de células escamosas del tracto aerodigestivo superior, seguido en frecuencia por el cáncer de pulmón y otras neoplasias. Afecta a la piel en tres etapas que tienen un comportamiento paralelo al crecimiento del tumor. En dos tercios de los casos, las lesiones cutáneas preceden a los síntomas o al diagnóstico del tumor. De ahí la importancia de la sospecha de esta entidad, que puede desenmascarar a la neoplasia asociada en una etapa temprana. Su tratamiento consiste en tratar la neoplasia subyacente. La recurrencia de las lesiones cutáneas puede revelar la recaída del tumor. Comunicamos el caso clínico de un paciente de sexo masculino en el cual el hallazgo de este síndrome permitió realizar el diagnóstico de un adenocarcinoma de pulmón, lo cual destaca la importancia de conocer a esta rara enfermedad y su asociación con cáncer, para poder realizar el diagnóstico oncológico de forma temprana y oportuna.

Adult-onset linear IgA bullous dermatosis: a retrospective single-center cohort study of 81 patients and literature review.

BACKGROUND: Linear IgA bullous dermatosis (LABD) is a rare autoimmune blistering disorder that may be drug-induced or paraneoplastic. We aim to characterize features of LABD and determine differentiating factors among idiopathic, drug-induced, or malignancy-associated diseases. METHODS: We conducted a single-center retrospective chart review of adult patients with linear IgA bullous dermatosis at a large tertiary referral center and a literature review of adult linear IgA bullous dermatosis. RESULTS: Eighty-one patients were included in the study. Ten patients (12.3%) had comorbid malignancy and nine (11.1%) had inflammatory bowel disease. Median disease duration was significantly shorter in both drug-induced (1.2 vs. 48.8 months; P < 0.001) and malignancy-associated (1.7 vs. 48.8 months; P < 0.001) LABD compared with idiopathic LABD. Recurrent episodes occurred significantly more often in idiopathic LABD compared to those with drug-induced (76.1 vs. 11.5%; P < 0.001) or malignancy-associated disease (76.1 vs. 33.3%; P = 0.019). Time to diagnosis was significantly shorter in the drug-induced (0.2 vs. 5.4 months; P < 0.001) and malignancy-associated groups (0.7 vs. 5.4 months; P = 0.049) compared with idiopathic; similarly, time to improvement was significantly shorter in both drug-induced (0.4 vs. 3.0 months; P < 0.001) and malignancy-associated disease (1.1 vs. 3.0 months; P = 0.016). Clinical morphology was indistinguishable between groups. Limitations included retrospective data collection, data from tertiary referral centers, and limited racial and ethnic diversity. CONCLUSION: Screening for underlying malignancy, as well as for a predisposing medication or possibly inflammatory bowel disease, may be advisable in patients with LABD, particularly when it is newly diagnosed.

Management of Paraneoplastic Syndromes in the Era of Immune Checkpoint Inhibitors.

OPINION STATEMENT: Our understanding of paraneoplastic neurologic syndromes (PNS) has blossomed over the past few decades. Clinicians have access to more robust diagnostic criteria and have a heightened index of suspicion for these disorders. Nonetheless, treatment, which typically includes immunosuppression, and response to treatment, varies. Due to persistent difficulty in making a definitive diagnosis, we favor empiric treatment when a possible diagnosis of PNS is suspected, and other alternative causes have substantially been excluded (e.g., infections, toxic-metabolic derangements, metastasis, or leptomeningeal disease). Treatment of the underlying cancer, if identified, is the first therapeutic step and can prevent disease worsening and in rare cases, can reverse neurologic symptoms. In addition to anti-cancer treatment, first line immunotherapies, which include corticosteroids, intravenous immunoglobulins (IVIG), or plasma exchange (PLEX) are typically used. If partial or no benefit is seen, second line immunotherapeutic agents such as rituximab are considered. Additionally, the severity of the initial presentation and possible risk for relapse influences the use of the latter agents. Symptomatic management is also an important component in our practice and will depend on the syndrome being treated. One of the more novel entities we are facing currently is the management of immune checkpoint (ICI)-induced PNS. In those cases, current American Society of Clinical Oncology (ASCO) guidelines are followed.