Significant improvement in paraneoplastic neurological syndromes without identifiable anti-neural antibodies in patients with breast cancer after breast surgery.

Paraneoplastic neurological syndromes (PNS) are neurological disorders that occur in close association with tumors without direct metastasis or invasion of the tumors and in which anti-neural antibodies may be present. Cerebellar ataxia is a common form of PNS in patients with breast cancer. However, reports of symptom improvement with breast cancer treatment are more common in patients with positive anti-neural antibodies and are rarely seen in those with negative anti-neural antibodies. In addition, there have been few quantitative evaluations of symptom improvement. We report a case in which neurological symptoms significantly improved after surgical treatment for breast cancer. The patient was a 78-years-old woman with subacute progressive cerebellar ataxia. A subsequent diagnosis of breast cancer led to the diagnosis of "PNS probable". A comprehensive search for anti-neural antibodies was negative in all cases. The quantitative index of the Scale for the Assessment and Rating of Ataxia (SARA) score, a standard evaluation method for ataxia in spinocerebellar degeneration, improved after breast cancer surgery. This case may provide a rationale for treating breast cancer patients negative for anti-neural antibodies, with the possibility of improving neurological symptoms.

HLA-DR3 ~ DQ2 associates with sensory neuropathy in paraneoplastic neurological syndromes with Hu antibodies.

OBJECTIVES: To investigate the association between human leukocyte antigen (HLA) and paraneoplastic neurological syndromes (PNS) with Hu antibodies, and potential specificities according to clinical presentation and cancer status. METHODS: HLA genotypes at four-digit resolution were imputed from available genome-wide association data. Allele carrier frequencies were compared between patients (whole cohort, n = 100, and according to clinical presentation and cancer status) and matched healthy controls (n = 508) using logistic regression controlled by the three main principal components. RESULTS: The clinical presentation of 100 anti-Hu patients involved the central nervous system (28, 28%), the peripheral nervous system (36, 36%) or both combined (36, 36%). Cancer diagnosis was certain in 75 (75%). HLA association analyses revealed that anti-Hu PNS patients were more frequently carriers of DQA1*05:01 (39% vs. 19%, OR = 2.8 [1.74-4.49]), DQB1*02:01 (39% vs. 18%, OR = 2.88 [1.79-4.64]) and DRB1*03:01 (41% vs. 19%, OR = 2.92 [1.80-4.73]) than healthy controls. Remarkably, such DR3 ~ DQ2 association was absent in patients with pure central involvement, but more specific to those manifesting with peripheral involvement: DQA1*05:01 (OR = 3.12 [1.48-6.60]), DQB1*02:01 (OR = 3.35 [1.57-7.15]) and DRB1*03:01 (OR = 3.62 [1.64-7.97]); being even stronger in cases with sensory neuropathy, DQA1*05:01 (OR = 4.41 [1.89-10.33]), DQB1*02:01 (OR = 4.85 [2.04-11.53]) and DRB1*03:01 (OR = 5.79 [2.28-14.74]). Similarly, DR3 ~ DQ2 association was only observed in patients with cancer. DISCUSSION: Patients with anti-Hu PNS show different HLA profiles according to clinical presentation and, probably, cancer status, suggesting pathophysiological differences.

Case Report: Longitudinal Evaluation and Treatment of a Melanoma-Associated Retinopathy Patient.

Melanoma-associated retinopathy (MAR) is a paraneoplastic syndrome associated with cutaneous metastatic melanoma in which patients develop vision deficits that include reduced night vision, poor contrast sensitivity, and photopsia. MAR is caused by autoantibodies targeting TRPM1, an ion channel found in melanocytes and retinal ON-bipolar cells (ON-BCs). The visual symptoms arise when TRPM1 autoantibodies enter ON-BCs and block the function of TRPM1, thus detection of TRPM1 autoantibodies in patient serum is a key criterion in diagnosing MAR. Electroretinograms are used to measure the impact of TRPM1 autoantibodies on ON-BC function and represent another important diagnostic tool for MAR. To date, MAR case reports have included one or both diagnostic components, but only for a single time point in the course of a patient's disease. Here, we report a case of MAR supported by longitudinal analysis of serum autoantibody detection, visual function, ocular inflammation, vascular integrity, and response to slow-release intraocular corticosteroids. Integrating these data with the patient's oncological and ophthalmological records reveals novel insights regarding MAR pathogenesis, progression, and treatment, which may inform new research and expand our collective understanding of the disease. In brief, we find TRPM1 autoantibodies can disrupt vision even when serum levels are barely detectable by western blot and immunohistochemistry; intraocular dexamethasone treatment alleviates MAR visual symptoms despite high levels of circulating TRPM1 autoantibodies, implicating antibody access to the retina as a key factor in MAR pathogenesis. Elevated inflammatory cytokine levels in the patient's eyes may be responsible for the observed damage to the blood-retinal barrier and subsequent entry of autoantibodies into the retina.

Nephrotic syndrome associated with solid malignancies: a systematic review.

BACKGROUND: Nephrotic syndrome (NS) can occur as a paraneoplastic disorder in association with various types of carcinoma. However, paraneoplastic nephrotic syndrome (PNS) is often misdiagnosed as idiopathic nephrotic syndrome or as an adverse effect of oncology treatment, leading to delayed diagnosis and suboptimal treatment. The characteristics of NS associated with solid malignancies are not yet elucidated. We systematically summarized the clinical data for 128 cases of NS combined with solid malignancies with the aim of informing the clinical management of PNS. METHODS: We searched the PubMed database for articles published from the date of inception through to October 2023 using the following keywords: "cancer" or "malignant neoplasms" or "neoplasia" or "tumors" and "nephrotic syndrome", "nephrotic" or "syndrome, nephrotic". All data were extracted from case reports and case series, and the extraction included a method for identifying individual-level patient data. RESULTS: A literature search yielded 105 cases of PNS and 23 of NS induced by cancer therapy. The median age at diagnosis was 60 years, with a male to female ratio of 1.8:1. In patients with PNS, manifestations of NS occurred before, concomitantly with, or after diagnosis of the tumor (in 36%, 30%, and 34% of cases, respectively). Membranous nephropathy (49%) was the most prevalent renal pathology and found particularly in patients with lung, colorectal, or breast carcinoma. Regardless of whether treatment was for cancer alone or in combination with NS, the likelihood of remission was high. CONCLUSION: The pathological type of NS may be associated with specific malignancies in patients with PNS. Prompt identification of PNS coupled with suitable therapeutic intervention has a significant impact on the outcome for patients.

Paraneoplastic neuromyelitis optica spectrum disorder associated with ovarian dysgerminoma: a case report and literature review.

Neuromyelitis optica spectrum disorder (NMOSD) is a clinical syndrome characterized by attacks of acute optic neuritis and transverse myelitis. We report a case with paraneoplastic NMOSD that improved after immunosuppressive therapy, surgical resection, and chemotherapy. A 48-year-old woman initially presented with gradual binocular visual loss over the course of one week. The patient was evaluated using magnetic resonance imaging (MRI), computed tomography (CT), visual evoked potential (VEP), pathological biopsy, immunohistochemistry, and autoimmune antibody testing. The brain MRI findings were normal. The VEP revealed prolonged P100 latencies in the right eye and an absence of significant waves in the left eye. Positive serum AQP4-IgG antibodies were found. The patient was diagnosed as NMOSD. Then the patient responded well to treatment with methylprednisolone. An ovarian tumor was found in the patient using abdominal MRI and CT. The tumor was surgically resected, and a pathological biopsy revealed that it was ovarian dysgerminoma. The patient received four rounds of chemotherapy after surgery. One month after the final chemotherapy treatment, a positron emission tomography (PET) scan revealed no tumor. The vision of the patient gradually recovered and serum AQP4 was negative. Furthermore, we summarized the characteristics of patients diagnosed with paraneoplastic NMOSD associated with ovarian neoplasms in previous studies. This is a characteristic case of overlapping NMOSD and ovarian dysgerminoma, demonstrating the importance of tumor therapy in cases of paraneoplastic NMOSD.

Relapsing Anti-GAD65-Associated Encephalitis Responsive to Thymoma Resection, Radiation, and Immunomodulatory Therapy.

Herein we describe a case of relapsing anti-GAD65-associated encephalitis which was responsive to the combination of thymoma resection, external beam radiotherapy, and immunomodulatory therapy. The case illustrates the value of remaining vigilant for the possibility of paraneoplastic syndromes in the context of anti-GAD65 antibodies and thymoma. It also illustrates that tumor-directed therapies may offer additional benefit beyond immunomodulatory therapy alone.

Trismus as the Initial Presentation of Anti-Hu Paraneoplastic Neurological Syndrome.

A 73-year-old man presented with subacute trismus and pancerebellar dysfunction. Brain imaging and routine blood test results were unremarkable. Chest computed tomography revealed an indistinctly enhancing 4.7 × 2.5 × 1.8-cm3 pulmonary mass in the right upper lung, with enlarged right paratracheal and hilar lymph nodes. Biopsy of the right supraclavicular lymph node confirmed metastatic carcinoma, with differential diagnoses of small cell carcinoma and poorly differentiated carcinoma, indicating lung cancer as the primary source. Paraneoplastic immunohistochemistry screening revealed anti-Hu antibodies in the serum at a titer of 1:7680 (normal range <1:240) and in the cerebrospinal fluid (CSF) at a titer of 1:256 (normal range <1:2). The line blot method yielded positive results for anti-Zic4 antibodies in serum, with a titer of >1:10 (normal range <1:10), whereas CSF anti-Zic4 was negative (normal range <1:2). The patient developed non-responsive hospital-acquired pneumonia and respiratory failure, and discharged himself against medical advice. This rare case indicates that trismus can be an initial manifestation of anti-Hu paraneoplastic neurological syndrome, and emphasizes the importance of clinical awareness.

Case report: Chronic disseminated intravascular coagulopathy with concurrent paraneoplastic secondary hyperfibrinolysis in a dog with metastatic nasal adenocarcinoma.

In human medicine, hemostatic disorders such as thrombocytopenia, hyperfibrinolysis, and disseminated intravascular coagulopathy (DIC) have been associated with many cancers. Acute hemorrhage secondary to hyperfibrinolysis has been predominantly reported with prostatic adenocarcinoma in human patients. To the author's knowledge, severe bleeding due to paraneoplastic hyperfibrinolysis has not yet been reported in veterinary medicine. The case involves an 8-year-old neutered male Border Collie who was evaluated for progressive and recurrent epistaxis, having a history of 1 year of treatment for metastatic nasal adenocarcinoma. A progressive and severe coagulopathy thought to be related to the known cancer was diagnosed. Advanced coagulation testing was consistent with a chronic DIC and secondary hyperfibrinolysis. Throughout 1 week of hospitalization, the dog was treated with multiple blood products, vitamin K1, and anti-fibrinolytic medications. While the dog was initially discharged home, the dog re-presented the following day and was humanely euthanized due to a perceived poor quality of life. Post-mortem analysis revealed a histopathologic diagnosis of disseminated adenocarcinoma. In dogs with disseminated nasal adenocarcinoma that are experiencing severe bleeding, paraneoplastic secondary hyperfibrinolysis should be considered as a differential. Knowing this association could help guide treatment recommendations for optimal patient management.

Addressing recurrent hypoglycaemia through thoracic surgical intervention: understanding Doege-Potter syndrome, a rarity in syndromes.

Doege-Potter syndrome (DPS), a rare paraneoplastic phenomenon characterised by non-islet cell tumour hypoglycaemia (NICTH), presents clinicians with intricate diagnostic and therapeutic challenges. This comprehensive review consolidates current understanding, clinical presentations, diagnostic modalities, therapeutic interventions, and emerging trends in managing DPS. The pathophysiology of DPS revolves around dysregulated insulin-like growth factors (IGF), particularly IGF-2, produced by mesenchymal tumours, notably solitary fibrous tumours (SFT). Clinical manifestations encompass recurrent hypoglycaemic episodes, often distinct from typical hypoglycaemia, with implications for insulin and counterregulatory hormone levels. Diagnosis necessitates a multidisciplinary approach integrating biochemical assays, imaging studies, and histopathological confirmation of the underlying neoplasm. Surgical resection remains the cornerstone of treatment, complemented by adjunctive therapies to manage persistent hypoglycaemia. Prognosis is influenced by successful tumour resection and long-term surveillance for recurrence. A patient-centred approach, incorporating supportive services and multidisciplinary care, is essential for optimal outcomes in individuals affected by DPS.

Acute Glomerulonephritis as a Paraneoplastic Syndrome Secondary to Urachal Adenocarcinoma: An Unknown Entity.

Urachal carcinoma is an uncommon malignancy with a peculiar biomolecular characterization and therefore a complex approach. It was incorporated by the World Health Organization in 2004 in the tumors of the urinary system classification. This neoplasm is generally diagnosed in advanced stages. The standard treatment is surgical, however, due to the rarity and relatively late clinical manifestation of urachal carcinomas, the survival data are mostly case reports, as well as information about medical-surgical treatment based on evidence. The data used were extracted from both the physical and electronic clinical records. Among atypical presentations reported in the literature, we report a case of urachal adenocarcinoma with simultaneous glomerulonephritis as a paraneoplastic syndrome of which there is no report to date. Surgery was carried out in our patient, unfortunately with lifetime morbidity from kidney function replacement secondary to kidney function damage by glomerulonephritis, despite previous immunosuppression treatment for rapidly progressive glomerulonephritis. It is worth mentioning that if the initial diagnosis represents a clinical challenge, treatment is even more complex, given the little information that currently exists about it. Urachal carcinoma is a diagnostic and treatment challenge. Up to now, surgery has been the treatment of choice in localized or locally advanced disease, however, with a high morbidity for the patient.

Paraneoplastic Cerebellar Degeneration Revealing Non-Small Cell Lung Cancer: A Case Report.

Paraneoplastic neurologic degeneration (PND) manifests as a sudden or subacute neurological syndrome often linked to underlying cancer, either overt or subclinical. Within the spectrum of PND, subacute paraneoplastic cerebellar degeneration (PCD) represents a distinctive subset. While rare, prompt diagnosis holds the potential to ameliorate both neurological and oncological outcomes. Herein, we present the case of a 61-year-old patient diagnosed with subacute cerebellar degeneration, ultimately unveiling non-small cell lung carcinoma.

Neurological Immune-Related Adverse Events Induced by Immune Checkpoint Inhibitors.

The use of immune checkpoint inhibitors (ICIs) for the treatment of various advanced and aggressive types of malignancy has significantly increased both survival and long-term remission rates. ICIs block crucial inhibitory pathways of the immune system, in order to trigger an aggravated immune response against the tumor. However, this enhanced immune activation leads to the development of numerous immune-related adverse events (irAEs), which may affect any system. Although severe neurological irAEs are relatively rare, they carry a high disability burden, and they can be potentially life-threatening. Therefore, clinicians must be alert and act promptly when individuals receiving ICIs present with new-onset neurological symptoms. In this narrative review, we have collected all the currently available data regarding the epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of post-ICI neurological irAEs. This review aims to raise physicians' awareness, enrich their knowledge regarding disease pathogenesis, and guide them through the diagnosis and management of post-ICI neurological irAEs.

Hide-and-Seek With Spindle-Cell-Component-Poor Metaplastic Thymoma.

Metaplastic thymoma is a rare biphasic thymic tumor with indolent behavior and recurrent YAP1::MAML2 gene rearrangement. Although the diagnosis of this tumor is usually straightforward based on hematoxylin and eosin (H&E) findings alone, cases with scant spindle-cell ("pseudosarcomatous stroma") components can be easily confused with more commonly occurring type A thymoma. We present a case of metaplastic thymoma with a sparse stroma-like spindle-cell component, discussing its histological and immunohistochemical hints and drawing attention to the visual similarity to type A thymoma. This is also the first published case of metaplastic thymoma with associated psoriasis.

Paraneoplastic leukocytosis secondary to carcinosarcoma: a report of two cases and literature review.

BACKGROUND: Neutrophilia is an increase in the number of neutrophils over 7.5×103/µL. An increase in leukocytes over 50×103/µL is called a leukemoid reaction; and when it is associated with a solid tumor, it is considered a paraneoplastic syndrome called paraneoplastic leukemoid reaction (PLR). It is a very rare clinical condition and it is very unusual for it to be associated with carcinosarcoma. We present two cases of a leukemoid reaction observed in the Medical Oncology Department of the University Hospital of Salamanca between May and September 2023. The main objectives of our article are to describe the unusual appearance of paraneoplastic leukocytosis at the diagnosis of carcinosarcoma carcinosarcoma, explain in a detailed way its diagnostic procedure and to show the poor prognosis to which it is associated. CASE DESCRIPTION: In our presentation, we describe two similar cases: first of all, a 60-year-old woman without relevant medical history. She was referred by her primary physician to the Department of Internal Medicine in August 2023 with asthenia, lumbar pain, and weight loss of 12 kg of 3 months of evolution. The physical examination revealed a palpable hypogastric mass. An abdominal, pelvic, and thoracic computed tomography (CT) scan revealed a heterogenous solid mass with necrotic areas originating in the uterus. The anatomopathological diagnosis was carcinosarcoma. The patient showed a progressive worsening in her renal function associated with hyperviscosity secondary to hyperleukocytosis caused by 170×103/µL neutrophils. In the second case we describe the diagnosis of a PLR secondary to a kidney carcinosarcoma. When the patient started chemotherapy, he presented 55.08×103/µL leukocytes, 53.16×103/µL neutrophils. Eight days after receiving chemotherapy, the patient was admitted as an emergency with oligoanuria and decreased consciousness. He presented creatinine 6.25 mg/dL, phosphate 12.4 mg/dL, leukocytes 1.05×103/µL, and neutrophils 0.71×103/µL. The clinical diagnosis was acute exacerbation of multifactorial mixed (renal and prerenal) chronic kidney disease associated with tumor lysis syndrome and grade 3 neutropenia. The patient presented a poor evolution, dying after 2 months. CONCLUSIONS: PLR is a severe paraneoplastic syndrome associated with different types of solid tumors. Its appearance at the time of diagnosis of a tumor implies a poor vital prognosis.

Systemic Capillary Leak Syndrome as a Paraneoplastic Syndrome.

Systemic capillary leak syndrome (SCLS) is a rare entity that is frequently idiopathic or, rarely, associated with infections, autoimmune diseases, drugs, surgery, and cancer. Several cancers can directly cause SCLS, although it is very uncommon as the inaugural presentation of a non-Hodgkin lymphoma. We report a case of SCLS as a paraneoplastic syndrome which revealed a large B-cell lymphoma, a non-Hodgkin lymphoma of B-cell origin.

Understanding Palmar Fasciitis and Polyarthritis Syndrome as a Rheumatologic Paraneoplastic Syndrome: A Case Report.

Palmar fasciitis and polyarthritis syndrome (PFPAS) is an exceedingly rare rheumatologic condition characterized by fibrotic changes in the palmar fascia with joint pains. It is known to be associated with gynecological malignancy, especially ovarian adenocarcinoma, gastric cancer, pancreatic, prostate, breast, and lung cancer. We present a unique case of a 75-year-old Caucasian female with PFPAS preceding the diagnosis of ovarian cancer by eight months. Our case highlights the importance of considering PFPAS as a potential paraneoplastic syndrome. It underscores the need for increased awareness and further studies to enhance the early detection of underlying malignancies in patients presenting with similar nonspecific hand symptoms.

Paraneoplastic Leukemoid reaction in soft tissue sarcoma: A case report and literature review.

INTRODUCTION: Paraneoplastic leukemoid reactions (PLRs) in the context of sarcomas represent a unique clinical entity that poses significant diagnostic challenges and adds valuable insights to the surgical literature. Characterized by an abnormal elevation of white blood cell count, these reactions are often associated with aggressive tumor biology and poor prognosis, emphasizing the need for heightened awareness among clinicians. CASE PRESENTATION: A 48-year-old male presented with a rapidly growing, ulcerated tumor on his thigh. Lab tests revealed an extreme leukocytosis with a white blood cell count of 92,860/mm3. Imaging and biopsy confirmed a high-grade spindle cell sarcoma. CLINICAL DISCUSSION: After excluding other causes of leukocytosis, a PLR secondary to sarcoma was diagnosed. Despite initial antibiotic treatment, leukocytosis persisted, prompting a decision for surgical intervention. The patient underwent successful tumor resection, resulting in a significant decrease in leukocyte count and subsequent stable recovery, supported by adjuvant radiotherapy. CONCLUSION: This case underscores the importance of recognizing PLRs in sarcoma patients as they can significantly impact clinical management and prognosis. It highlights the necessity of a multidisciplinary approach for accurate diagnosis and effective treatment. The case contributes to the surgical literature by detailing the diagnostic process and therapeutic interventions in managing such complex presentations, thereby providing key "take-away" lessons on the importance of considering PLRs in the differential diagnosis of leukocytosis in patients with malignancies.

A Cadaveric Case of Bilateral Adrenal Hyperplasia With Lung Cancer: A Paraneoplastic Syndrome?

Bilateral adrenal hyperplasia associated with primary lung cancer may arise from either an adrenocorticotropic hormone (ACTH)-dependent paraneoplastic syndrome or metastatic hyperplasia. Ectopic Cushing's syndrome manifests as a paraneoplastic syndrome characterized by the secretion of ACTH from malignant cells. This secretion can in turn overstimulate the adrenal cortex, resulting in adrenal cortical hyperplasia followed by hypercortisolism. Though rare, lung cancer can metastasize to the adrenal glands bilaterally, occasionally resulting in hemorrhage causing a rapid increase in size. This cadaveric report aims to delineate an unusual case of metastatic lung cancer, presenting with bilateral adrenal hyperplasia and two abdominal aortic aneurysms (AAA). An 84-year-old white male cadaver was dissected during routine coursework. Dissection of the right lung revealed a pale-yellow mass measuring 10.0 x 7.4 x 7.0cm. An irregularly defined, necrotic, ulcerated lesion measuring 5.5 x 4.5 x 3.3cm was evident on the lateral surface of the left shoulder, consistent with a history of metastatic lung carcinoma. Upon abdominal dissection, bilaterally enlarged adrenal glands and two AAAs were observed. These AAAs measured 6.0cm and 11.0cm at their respective widest transverse diameters. The right and left adrenal glands measured 10.0 x 6.5 x 4.5cm and 7.3 x 4.7 x 3.5cm, respectively. We aim to discuss the possible pathophysiological correlation of these unusual findings in this cadaver.