Initial Presentation of Ovarian Carcinosarcoma With Non-islet Cell Tumor Hypoglycemia: A Case Report.

Ovarian cancer, although not among the most commonly diagnosed cancers, remains a significant cause of cancer-related mortality in females. Several paraneoplastic syndromes have been associated, and this case study represents a rare manifestation of ovarian cancer, presenting as non-islet cell tumor hypoglycemia (NICTH), characterized by the excessive production of insulin-like growth factor-II (IGF-II) by tumor cells. We report a 55-year-old woman who presented to our hospital with abdominal distension and severe refractory hypoglycemia. The laboratory data revealed the suppression of serum insulin and C-peptide levels. The insulin-like growth factor II (IGF-II)/insulin-like growth factor 1 (IGF1) ratio was >32. The hypoglycemia was hence attributed to the non-islet cell tumor type, and it is likely driven by tumoral secretion of incompletely processed IGF-II. The lab findings suggested the existence of NICTH. Abdominal computed tomography demonstrated the presence of a left ovarian mass and peritoneal carcinomatosis. CT-guided biopsy of the peritoneal lesions showed poorly differentiated malignancy consistent with ovarian carcinosarcoma (OCS). The patient was treated with a continuous infusion of glucose. She even received oral prednisone and glucagon infusion. Chemotherapy with carboplatin and paclitaxel was initiated, but unfortunately, she died from complications of multiorgan failure. To our knowledge, this is the first novel case of an initial presentation of metastatic OCS with NICTH, underscoring the complexity of ovarian cancer presentations and the necessity of a comprehensive approach in managing rare paraneoplastic syndromes, such as NICTH.

Paraneoplastic Syndrome Prevalence and Survival in Racially-Diverse Cohort With Renal Cell Carcinoma.

INTRODUCTION: The prevalence of preoperative paraneoplastic syndromes (PNS) in renal cell carcinoma (RCC) is poorly understood. Many laboratory abnormalities representative of PNS have demonstrated prognostic value when incorporated into predictive survival models in RCC. We sought to characterize the relationship between baseline prevalence of PNS with overall survival (OS) and cancer-specific survival (CSS) in RCC patients following nephrectomy. METHODS: Our prospectively maintained nephrectomy database was retrospectively reviewed for any stage, major histology RCC patients that underwent surgery from 2000 to 2022. Baseline laboratory values within 90 days (closest used) were required. Presence of PNS was defined according to established laboratory cutoffs. Kaplan-Meier curves estimated survival rates, and multivariable Cox proportional hazards models examined the association between PNS with OS and CSS following nephrectomy. RESULTS: 2599 patients were included with listed staging: 1494 Stage I; 180 Stage II; 616 Stage III; 306 Stage IV. Proportion of patients presenting with >1 PNS significantly increased from stage I (31.3%) to stage IV (74.2%) RCC (P < .001). Elevated C-reactive protein was the most prevalent PNS (45.4%). On multivariable analysis, the presence of >1 PNS was associated with higher risk of all-cause (HR 2.09; P < .001) and cancer-specific mortality (HR 2.55; P < .001). The 10-year OS estimates as reported: 65.2% (no PNS), 52.3% (1 PNS), 36.6% (>1 PNS); and 10-year CSS estimates: 88.3% (no PNS), 79.3% (1 PNS), 61.6% (>1 PNS). DISCUSSION: Increased prevalence of PNS in major histology RCC was associated with a significant increase in the risk of all-cause and cancer-specific mortality even when accounting for patient and disease characteristics.

Stiff-person syndrome in association with Hashimoto's thyroiditis: a case report.

Stiff-person syndrome (SPS) is a rare neurological disorder characterized by chronic and progressive axial muscle rigidity and paroxysmal painful muscle spasms. The present case study described an SPS patient (increased anti-GAD65 antibody in serum and cerebrospinal fluid) with co-occurring Hashimoto's thyroiditis and decreased C3 complement levels. The clinical presentation, diagnostic approach, and treatment employed for this unique case were comprehensively described in detail. In this case, we comprehensively presented a case of SPS with co-occurring Hashimoto's thyroiditis and an associated decrease in serum C3 complement, as well as a discussion on the current data on this topic.

The Broad Spectrum of Gallbladder Paraneoplastic Syndromes.

Gallbladder carcinoma (GBC) is a rare gastrointestinal tumor with a reported incidence of 1 in 100,000 in the United States. GBC may present with subtle signs and symptoms that can be missed on routine examination and/or confused with other conditions. Unfortunately, its subtle presentation frequently leads to late diagnosis and, thus, a poor prognosis. Several paraneoplastic syndromes have been associated with GBC. Despite their strong associations with neoplastic disease, the precise pathophysiologic mechanisms underlying the development of these syndromes remain poorly understood. Given the vague nature of their initial signs and symptoms, these syndromes are frequently diagnosed as independent entities and only later associated with occult malignancies that may have already metastasized to other organs. Physicians need to be aware of the signs and symptoms of these paraneoplastic syndromes and include an underlying malignancy as part of the differential diagnosis. This review provides a detailed discussion of the paraneoplastic syndromes associated with GBC.

Trousseau's Syndrome: A Paraneoplastic Complication.

Trousseau syndrome, also known as thrombophlebitis migrans or migratory superficial thrombophlebitis, is a rare but significant paraneoplastic manifestation associated with various cancers. This syndrome is characterized by the occurrence of recurrent deep or superficial venous thrombosis in patients with malignancies. Patients with cancer have a greatly increased risk of venous thrombosis, especially in the first few months after diagnosis and in the presence of distant metastases. This article describes the case of a 72-year-old female patient who suffered a deep vein thrombosis in the right lower limb, which led to Trousseau syndrome secondary to non-Hodgkin's lymphoma.

Thymoma-Associated Pleural Effusion Treated With Neoadjuvant Chemotherapy.

Anterior mediastinal masses, including thymomas, can present with thoracic symptoms or paraneoplastic syndromes, especially in adults over 40. Diagnosis involves imaging and biopsy, and treatment includes surgical resection and chemotherapy, depending on the stage. A 31-year-old male, with a history of alcohol use disorder and a former smoker, presented with increasing heartburn, shortness of breath, left shoulder pain, and chest pain. Imaging revealed an anterior mediastinal mass with pleural thickening and a small effusion. A biopsy confirmed a B2-type thymoma. Initial treatment included cyclophosphamide, doxorubicin, and cisplatin, resulting in significant tumor reduction and pleural effusion resolution. The patient underwent planned surgical resection following neoadjuvant chemotherapy. This case highlights the complexity of advanced thymoma treatment and the effectiveness of neoadjuvant chemotherapy in reducing tumor burden, the associated effusions, and improving outcomes. Continuous follow-up and further studies are essential to optimize treatment protocols for advanced thymoma.

Metastatic Small Cell Carcinoma of the Bladder Complicated by Paraneoplastic Acute Thrombocytopenia.

Small cell carcinoma of the bladder is an extremely rare and aggressive disease with poor overall survival, as it is often diagnosed in later stages. Similarly, paraneoplastic thrombocytopenia is also a rare phenomenon infrequently described in the literature. Given its rarity but responsiveness to chemotherapy, awareness of atypical presentations helps facilitate appropriate treatment. A 76-year-old gentleman was admitted to an Australian regional hospital from a small remote hospital with complaints of five months of anorexia, lethargy, weight loss, and new-onset pleuritic chest pain with a past medical history of prostatomegaly and a distant history of localised seminoma treated with surgical resection and radiotherapy alone. Physical examination revealed new rapid atrial fibrillation and mild hypoxia alongside right upper quadrant tenderness and fullness. The patient underwent pleural drainage, cytology, and computed tomography, was subsequently diagnosed with small cell carcinoma of the bladder, and rapidly developed isolated thrombocytopenia that improved with inpatient chemotherapy with carboplatin/etoposide. He was eventually discharged home after a lengthy admission. On follow-up, he had cycle 2 of treatment as an outpatient before undergoing palliative treatment at the patient's small remote hospital. This highlights the importance of both prompt recognition and treatment of rapidly growing small cell carcinomas when they first present atypically with uncharacteristic paraneoplastic syndromes to reduce morbidity and mortality.

Angiography Revealing a Possible Paraneoplastic Vasculitis: A Case Report.

Various conditions under the umbrella term of vasculitis have been well documented in the literature. These have been classified into small, medium, and large vessel vasculitis. In addition, vasculitis has been categorized into radiation-induced, systemic, and paraneoplastic. Of these, paraneoplastic vasculitis accounts for 2-5% of all cases of vasculitides and is less well documented. We present a case of a female patient with a history of breast cancer presenting with an upper gastrointestinal tract (GI) bleed, which subsequently revealed an underlying diagnosis of systemic vasculitis, possibly paraneoplastic. This case highlights the importance of imaging for revealing underlying vasculitis as an etiology of GI bleed.

Focal Seizures Induced by Paraneoplastic Syndrome Leading to a Diagnosis of Small Cell Lung Carcinoma.

Paraneoplastic neurological disorders are a rare complication of multiple neoplasms, such as lung, testis, and breast, and can be associated with positive antibody anti-Hu (anti-neuronal nuclear antibody type 1 or ANNA-1), anti-Ta, anti-Ma, and uncharacterized antibody, or be antibody-negative. Early treatment of the underlying tumor is the most likely modality that will lead to regression of the paraneoplastic neurological symptoms. Here, we present a case of a 73-year-old female with new-onset seizure activity from ANNA-1 encephalitis found to have undiagnosed small cell lung cancer to highlight the need for further workup for malignancy.

Clinical and epidemiologic characteristics of hospitalized oncological patients with hypercalcemia: a longitudinal, multicenter study.

BACKGROUND: There are few studies that have analyzed the characteristics of hypercalcemia in hospitalized oncological patients. Our objectives were to describe the clinical characteristics of hospitalized patients with paraneoplastic hypercalcemia and to identify prognostic variables for mortality. METHODS: This was an observational, longitudinal, retrospective, and bicentric study. It included adult patients admitted to two hospitals in Málaga, Spain (2014-2018). The minimum follow-up period was 2 years or until death. RESULTS: A total of 154 patients were included; the majority (71.4%) were admitted to the internal medicine department. The median follow-up was 3.5 weeks (interquartile range [IQR] 1.1-11.5). The mean (standard deviation) age was 67.6 (12.3) years, with a predominance of males (58.4%). The median (IQR) serum calcium at admission was 13.2 (11.8-14.6) mg/dl. The most common neoplasms were pulmonary (27.3%), hematologic (23.4%), urological (13%), and breast (12.3%). Furthermore, 56.5% of cases had a known history of neoplasia at the time of diagnosis. The parathyroid hormone (PTH) level was determined in 24%; of these, 10.8% had elevated levels. In all, 95.5% of patients died during follow-up. The median survival was 3.4 weeks (95% confidence interval 2.6-4.3). Factors associated with higher mortality were age, serum calcium at admission, previous history of neoplasia, etiology other than multiple myeloma, and noncorrection of hypercalcemia. CONCLUSIONS: In hospitalized patients, paraneoplastic hypercalcemia was associated with high short-term mortality. Several factors associated with a worse prognosis were identified in these patients.

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.

Coexistence of myasthenia gravis and lichen planus: A case report and systematic review of related case reports from 1971 to 2024.

Key Clinical Message: The co-occurrence of myasthenia gravis (MG) and lichen planus (LP) is a rare phenomenon, with only 13 cases reported in the English literature between 1971 and 2024. Patients with MG or LP, regardless of the thymoma status, require close monitoring for other autoimmune diseases. Abstract: Myasthenia gravis (MG) is an uncommon autoimmune disease, resulting in fatigable muscle weakness in the ocular, bulbar, and respiratory muscles, as well as muscles of the extremities. Lichen planus (LP) is an autoimmune mucocutaneous disease, presenting with pruritic and violaceous plaques on the skin and mucosal surfaces. So far, MG and LP co-occurrence is only reported in anecdotal individuals. This study reports a patient with MG and LP and systematically reviews the English literature on this rare co-occurrence from 1971 to 2024, indicating only 13 cases with similar conditions. A 67-year-old man presented with ocular and progressive bulbar symptoms, a year after being diagnosed with generalized LP. Laboratory evaluations were normal except for the high anti-AchR-Ab titer and a positive ANA titer. Neurologic examinations revealed asymmetric bilateral ptosis, weakness and fatigability in proximal muscles, and a severe reduction in the gag reflex. He was diagnosed with late-onset, seropositive MG. The treatment included pyridostigmine (60 mg, three times daily), intravenous immunoglobulin (25 g daily for 5 days), and oral prednisolone. There was no evidence of thymoma in the chest x-ray and CT scan without contrast. However, a CT scan with contrast was not performed due to the patient's unstable condition. A common autoimmune mechanism may underlie the unclear pathophysiology of MG and LP co-occurrence, with or without thymoma. Patients with MG, LP, or thymoma require close monitoring and assessment for other possible autoimmune diseases.

A Case of MET Exon 14 Skipping Mutation: Positive Lung Adenocarcinoma Complicated by Paraneoplastic Neurological Syndrome.

A 67-year-old man with cervical spondylotic myelopathy undergoing conservative treatment presented with subacute progression of fine motor and ambulatory disturbances, leading to admission at a previous hospital. Pre-cervical laminoplasty chest computed tomography (CT) revealed a tumor in the left upper lobe of the lung, prompting transfer to our institution. Transbronchial biopsy findings were consistent with adenocarcinoma, diagnosed as clinical stage T2bN0M0, Stage IIA. The neurological abnormalities could not be solely attributed to cervical spondylotic myelopathy, leading to a diagnosis of concurrent paraneoplastic neurological syndrome (PNS). During hospitalization, the patient's condition progressed to a state of constant bed rest within two weeks. On the 17th hospital day, a left upper lobectomy was performed, resulting in significant improvement, allowing the patient to ambulate with assistance after two weeks, and transfer to a convalescent rehabilitation hospital on the 58th hospital day. Subsequent cancer multigene panel testing revealed a positive MET exon 14 skipping mutation. Given the absence of reports on this mutation in lung adenocarcinoma associated with PNS, we consider it rare and thus report this case.

Antibody-positive autoimmune encephalitis and paraneoplastic neurological syndrome: A Swedish case series.

OBJECTIVE: This study aimed to explore the clinical characteristics and temporal disease course of patients with autoimmune encephalitis (AE) and paraneoplastic neurological syndrome (PNS) in Sweden. METHODS: Thirty-seven antibody-positive AE and PNS cases were identified in the Healthcare region Mid Sweden between 2015 and 2019. Clinical data were collected through a retrospective review of electronic health records. Patients were divided into three subgroups based on antibody type: neuronal surface antibodies (NSAbs), onconeural antibodies, and anti-GAD65 antibodies. RESULTS: Nineteen patients had NSAbs, 11 onconeural antibodies, and seven anti-GAD65 antibodies. Anti-LGI1 and anti-NMDAR were the most frequently detected NSAbs, with anti-NMDAR cases having an older-than-expected age distribution (median age 40, range 17-72). Only 11 of 32 (30%) of patients had findings suggesting encephalitis on initial MRI, but 28 of 31 (90%) had pathological findings on initial cerebrospinal fluid analysis. All patients but one had abnormal EEG findings. Median time to immunotherapy was comparable among the three subgroups, whereas patients with anti-LGI1, anti-CASPR2, and anti-IgLON5 had an eightfold longer time to immunotherapy than anti-NMDAR and anti-GABA-B (p = .0016). There was a seasonal variation in onset for patients with non-tumor-related NSAbs and anti-GAD65 antibodies, with most patients (72%) falling ill in spring or summer. CONCLUSION: Swedish patients with AE and PNS had similar clinical characteristics as previously described cohorts from other geographical regions except for anti-NMDAR encephalitis, with older onset than expected. The onset of non-tumor-related AE occurred predominantly in the warm seasons, and AE with a more insidious onset was associated with delayed treatment initiation.

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.

Testicular Cancer and Paraneoplastic Encephalitis: A Review of the Current Literature.

INTRODUCTION: Paraneoplastic encephalitis (PE) represents a rare but significant complication in patients with testicular cancer (TC). Given the paucity of comprehensive literature on this topic, our review seeks to consolidate current knowledge and provide evidence-based recommendations for the diagnosis, prognosis, and management of PE in the context of TC. MATERIALS AND METHODS: In adherence to PRISMA guidelines, a systematic literature review was conducted from 1950 to April 2024 using PubMed. The search focused on articles where TC was identified as the primary etiology of PE. The Mixed Methods Appraisal Tool and the Oxford Centre for Evidence-Based Medicine's levels of evidence tool were employed for assessing study quality, and a thematic analysis was conducted to identify trends and patterns. RESULTS: Out of 91 articles identified, 29 met the inclusion criteria, encompassing 5 retrospective chart reviews, 3 case series, and 22 case reports. Findings indicate that PE symptoms can manifest at any stage of TC-before tumor detection, during treatment, or even years posttreatment. A notable observation was the frequent oversight of microscopic testicular tumors in ultrasound imaging, leading to diagnostic delays. The outcomes of PE in the context of TC were diverse, reflecting the heterogeneity of the studies included. CONCLUSION: PE, although rare, is a critical consideration in patients with TC presenting with neuropsychiatric symptoms. Early recognition and appropriate diagnostic workup, including consideration for microscopic neoplasms, are essential for timely intervention and improved patient outcomes.