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Solitary fibrous tumours (SFTs) are a rare mesenchymal neoplasm with an incidence of 2.8 per 100 000 of which only 1% occur in the female genital tract. Doege-Potter syndrome is a paraneoplastic phenomenon associated with approximately 5%–10% of SFTs and is characterised by non-islet cell hypoglycaemia due to tumour production of low molecular weight insulin-like growth factor-II. We present the fourth confirmed case of female pelvic SFT with Doege-Potter syndrome and a literature review.

Background: Measurement of parathyroid hormone related peptide (PTHrP) is helpful in the diagnosis and clinical management of patients suspected of humoral hypercalcemia of malignancy (HHM). In these patients uncontrolled release of PTHrP by tumor cells is responsible for the hypercalcemia and PTH concentrations are typically suppressed. Objective: Develop a sensitive and specific assay for quantitation of PTHrP in plasma. Method: Calibrators (PTHrP 1-86) and samples (50uL) were incubated with an anti-PTHrP goat polyclonal acridinium ester labeled antibody. Complexes were transferred and incubated in a microplate coated with an anti-PTHrP polyclonal rabbit antibody. After washing, the acridinium ester generated signal, which is directly proportional to the amount of PTHrP in sample, was quantified. Results: In this assay PTHrp was stable for 24 hours ambient, 3 days refrigerated, 34 days frozen and through 3 freeze/thaws. Intra and inter-assay imprecision in EDTA plasma (~0.16-35.0 pmol/L) ranged from 2.2-8.6% and 5-15%, respectively. The limit of detection was 0.04 pmol/L and the limit of quantitation was 0.16 pmol/L (15% CV). The analytical measuring range was 0.39-50.5 pmol/L (slope of 1.07 and r2 of 0.99). Average spike recovery was 98% (range 85-108%). The assay was not affected by hemoglobin of ≤500 mg/dL, triglycerides of ≤2000 mg/dL, or bilirubin of ≤50mg/dL. No hook effect was noted up to 500 pmol/L. PTH (1-84) did not cross-react in the assay. C-terminal PTHrP(107-139), and N-terminal PTHrP(1-36) had no significant cross-reactivity (≤1.1%). Mid-PTHrP(38-94) had 8.3% cross-reactivity. Comparison with an in-house PTHrP assay (n=267) showed an r2 of 0.96, and slope of 2.25 by Passing-Bablok regression fit. The 97.5% reference interval for PTHrP (n=114) was ≤0.7 pmol/L, however a higher concentration (≤4.2 pmol/L) was identified as a more specific clinical cut-off. A retrospective clinical validation study showed that using ≤4.2 pmol/L resulted in a 91% clinical sensitivity and a 98% clinical specificity. Conclusion: We have developed an analytically and clinically sensitive and specific PTHrP immunoassay. A cutoff of ≤4.2 pmol/L is clinically useful in the evaluation of patients suspected of hypercalcemia of malignancy.

Hypoglycaemia due to insulin-like growth factor (IGF)-2 secretion is a paraneoplastic complication of malignancy with significant morbidity that can often go unrecognised due to its uncommon presentation. We report on a case of a 51-year-old man with metastatic haemangiopericytoma presenting with refractory hypoglycaemia, requiring continuous dextrose 10% infusion while in hospital. IGF-2 levels were significantly elevated, in keeping with a rare entity associated with solitary fibrous tumours, known as Doege-Potter syndrome. The patient was managed using uncooked cornstarch in conjunction with debulking of the hepatic tumour burden with bland IR-guided transarterial embolisation, and eventual surgical resection to treat his non-islet cell tumour hypoglycaemia (NICTH). The case highlights this rare paraneoplastic phenomenon that should be included in the differential for hypoglycaemia, especially if a history of a solitary fibrous tumour is elicited. Our case is the first to document a successful approach to treating the hypoglycaemia using preoperative transarterial bland embolisation.

Paraneoplastic neurological syndrome (PNS) is a heterogeneous group of neurological disorders caused by immune-mediated inflammatory mechanisms. We herein report a 77-year-old man with CV2/CRMP5-antibody-related PNS associated with a gastrointestinal stromal tumor (GIST). He was admitted for forgetfulness and delusional behavior. His neurological symptoms were subacute, and a whole-body examination revealed a gastric GIST. Serology showed CV2/collapsin response mediator protein (CRMP)-5 antibodies. Partial gastrectomy was performed for the GIST, and the neurological symptoms and serum CV2/CRMP5 antibodies disappeared. No relapse has occurred since the surgery. PNS should be considered in patients with subacute neurological disorders.

Paraneoplastic neurological syndromes (PNS) can manifest with every type of malignancy. A well-known syndrome is myasthenia gravis (MG) in combination with thymomas. No association between primary brain tumors and neuromuscular disorders has been described. Here, we present a case of a 65-year-old patient who developed MG, following an uncomplicated, gross-total resection of a glioblastoma. To our knowledge, this is the first case describing the onset of MG during the early postoperative phase after glioblastoma resection. Current criteria of PNS are insufficient when the neurological syndrome is diagnosed at the time of a malignancy or shortly thereafter and should be revisited.

Tumor-induced osteomalacia TIO is a rare paraneoplastic syndrome caused by excessive production of fibroblast growth factor 23 FGF23 by a tumor. Previous studies have revealed generalized mineralization defects and low areal bone mineral density aBMD in TIO. However, data on the bone microarchitecture in TIO are limited. In this study, we evaluated the microarchitecture in the peripheral distal radius and tibia and axial lumbar spine skeleton using high-resolution peripheral quantitative computed tomography HR-pQCT and trabecular bone score TBS and investigated related factors in a large cohort of Chinese patients with TIO. A total of 186 patients with TIO who had undergone dual-energy X-ray absorptiometry DXA or HR-pQCT scans were enrolled. Compared with age-, sex- and BMI-matched healthy controls, TIO patients n=113 had lower vBMD, damaged microstructure and reduced bone strength in the peripheral skeleton, especially at the tibia. The average TBS obtained from 173 patients was 1.15 ± 0.16. The proportion of patients with abnormal TBS

Trousseau’s syndrome is a paraneoplastic syndrome and a pathological condition that causes cerebral stroke symptoms due to hypercoagulation associated with malignant tumours. There have been many cases of advanced lung cancer, but few reports have described surgery for lung cancer with Trousseau’s syndrome. We encountered a 76-year-old man suspected of having Trousseau’s syndrome associated with lung cancer. He was transferred to our hospital on the second day after the onset. After admission, he was treated with heparin and edaravone, and his condition improved. On the 12th day after the onset, we performed left pneumonectomy and lymph node dissection (ND2a-2). The final pathological results were adenocarcinoma, pathological stage was T4 (tumour size: 77 mm, pulmonary artery invasion) N1(#11, #12u) M0, stage IIIA. He has been recurrence free for 23 months since the surgery. In the future, we need to follow his condition carefully.

A 65-year-old man, a smoker, presented to the emergency department with progressive digital ischaemia, fever and weight loss. The clinical examination revealed generalised lymphadenopathy and ischaemic changes of the right distal phalanges of the second, third and fourth fingers. He had an ultrasound-guided biopsy of the cervical lymph node, which showed histopathological findings of classic Hodgkin’s lymphoma. Paraneoplastic acral vascular syndrome (PAVS) is a rare phenomenon and seen more in solid malignancies. There are very few reported cases of PAVS in haematological malignancies, including Hodgkin’s lymphoma. This case highlights the idea that the presence of acral vascular syndrome—especially in older patients—should alert physicians to search for an underlying malignancy as part of the medical evaluation. Also, it shows that medical treatment may slow the progress of the digital ischaemia until the culprit tumour has been identified and treated.

Background Immune checkpoint inhibitors (ICIs) as a cancer immunotherapy have emerged as a treatment for multiple advanced cancer types. Because of enhanced immune responses, immune-related adverse events (irAEs), including endocrinopathies such as hypophysitis, have been associated with the use of ICIs. Most underlying mechanisms of ICI-related hypophysitis remain unclear, especially for programmed cell death-1 (PD-1)/PD-1 ligand 1 (PD-L1) inhibitors. We hypothesized that ICI-related hypophysitis is associated with paraneoplastic syndrome caused by ectopic expression of pituitary-specific antigens. Methods Twenty consecutive patients with ICI-related hypophysitis between 2017 and 2019 at Kobe University Hospital were retrospectively analyzed. Circulating anti-pituitary antibodies were detected using immunofluorescence staining and immunoblotting. Ectopic expression of pituitary autoantigens in tumor specimens was also examined. Results Eighteen patients were treated with PD-1/PD-L1 inhibitors, and two were treated with a combination of cytotoxic T-lymphocyte antigen-4 (CTLA-4) and PD-1 inhibitors. All patients showed adrenocorticotropic hormone (ACTH) deficiency and additionally, three showed thyroid-stimulating hormone (TSH) deficiency, and one showed gonadotropin-releasing hormone (GnRH) deficiency. Among these patients, three exhibited anti-pituitary antibodies, two with anti-corticotroph antibody and one with anti-somatotroph antibody. Interestingly, the anti-corticotroph antibody recognized proopiomelanocortin (POMC) and those two patients exhibited ectopic ACTH expression in the tumor, while the patients without anti-corticotroph antibody did not. Conclusions We demonstrated 10% of PD-1/PD-L1 inhibitors-related hypophysitis were associated with the autoimmunity against corticotrophs and maybe caused as a form of paraneoplastic syndrome, in which ectopic expression of ACTH in the tumor was observed. It is also suggested that the pathophysiology is heterogenous in ICI-related hypophysitis.

Hypercalcemia of malignancy (HCM) is considered an oncologic emergency associated with significant symptom burden and increased comorbid conditions and mortality. Underlying pathologic processes most often stimulate osteoclast-mediated bone resorption. Although long-term control of HCM depends on effective management of the underlying cancer, temporizing management strategies for acute and/or symptomatic HCM include hydration and antiresorptive bone-modifying agents. Although most patients respond well to the antiresorptive therapies available, further investigation into other agents for those who are refractory to both bisphosphonates and denosumab is needed.

Purpose of review X-linked hypophosphatemia and tumor-induced osteomalacia are diseases characterized by hypophosphatemia with impaired proximal tubular phosphate reabsorption. Complete resection of responsible tumors is the first line therapy for patients with tumor-induced osteomalacia. In contrast, phosphate and active vitamin D have been used for patients with X-linked hypophosphatemia and inoperable ones with tumor-induced osteomalacia. The purpose of this review is to summarize the pathogenesis of these diseases and discuss about the new treatment. Recent findings Excessive FGF23 production has been shown to underline several kinds of hypophosphatemic rickets/osteomalacia including X-linked hypophosphatemia and tumor-induced osteomalacia. Burosumab, an anti-FGF23 monoclonal antibody, was approved for clinical use while the indications of burosumab are different depending on countries. Summary The inhibition of excessive FGF23 activity has been approved as a new therapy for several kinds of hypophosphatemic diseases. Further studies are necessary to clarify the long-term effects and safety of burosumab.

Paraneoplastic granulomatous disease occurs in approximately 7.3% of patients with non-Hodgkin lymphoma, most commonly among patients with chronic lymphocytic leukemia (CLL). These lesions are often reported to appear similar to sarcoidosis in clinical presentation and under light microscopy. However, comprehensive descriptions of the cytomorphologic characteristics of these paraneoplastic granulomas are lacking, and the mechanisms involved in their formation remain ill-defined. Noninfectious dermal granulomatous reactions have also been reported in many primary immunodeficiencies, including common variable immune deficiency and ataxia-telangiectasia. We present a case of noninfectious CD8+ predominant granulomatous dermatitis with ocular involvement occurring in the setting of CLL and marked hypogammaglobulinemia. Based on the analysis of shared factors in patients with primary immunodeficiencies and CLL, we conclude that the presence of pan-humoral immunodeficiency could itself be a risk factor for developing a CD8+ lymphogranulomatous reaction. This report and associated discussion evince that CD8+ predominant granulomatous reactions, distinct from sarcoidosis, may represent a previously unappreciated segment of the paraneoplastic granulomas observed in hematologic malignancies.

Ectopic production of adrenocorticotropic hormone (ACTH) by gastrointestinal neuroendocrine tumours (NETs) is relatively uncommon. We report a rare case of a liver metastatic G1 low-grade NET of the intestine that induced hypercortisolism after surgical resection. A 50-year-old man was admitted for an intestinal obstruction caused by a tumour of the intestine. Paraneoplastic Cushing syndrome was diagnosed more than a year later following the appearance of cushingoid symptoms, despite stable disease according to RECIST criteria but chromogranin A increase. Ketoconazole and sandostatin medical treatment and liver chemoembolization never managed to control the hypercortisolism unlike the bilateral adrenalectomy. The identification and effective management of this uncommon statement of ectopic ACTH secretion is important to improve the patient’s prognosis and quality of life.

Phosphaturic mesenchymal tumors (PMTs) are rare mesenchymal neoplasms of soft tissue or bone origin that can give rise to a challenge in diagnostic imaging. These tumors are frequently associated with tumor-induced osteomalacia, also called oncogenic osteomalacia, which is a rare paraneoplastic syndrome characterized by ectopic secretion of fibroblast growth factor 23, a hormone that regulates serum phosphate level. PMTs show polymorphic features on both radiological findings and histological examination, causing problems in diagnosis owing to their similarity with other mesenchymal tumors. Thus, this paper aims to describe radiological aspects of PMTs and suggest an imaging pathway for accurate diagnosis throughout the evidence from the literature review.

Malignant hypercalcemia is a paraneoplastic syndrome. It has been detected in several types of malignant tumors in dogs, such as lymphomas, and also in mammary neoplasms, without the exact determination of the mechanisms involved in its occurrence as well as its incidence. In this study, 100 bitches with mammary malignant neoplasia, diagnosed by histopathological analysis, were submitted to clinical evaluation for disease staging, hematological evaluation, serum biochemistry, including renal function tests, hepatic and total calcium serum levels and ionized fraction. These parameters were analyzed at the time of the initial attendance and 30 days after the treatment. The most frequent histological pattern was carcinoma in mixed tumors (26%). In 52% of the diseased dogs, hypercalcemia was observed by means of ionized calcium dosing, which was not verified by means of total calcium dosing, where only 4% presented hypercalcemia. No correlation was found between hypercalcemia and the histological pattern of the neoplasms. However, the correlation was verified between hypercalcemia and more advanced stages of the disease, mainly from stage III, suggesting that the detection of hypercalcemia may be correlated with worse prognosis, showing the importance of the research concerning the presence of paraneoplastic syndromes in bitches with mammary neoplasms.

Background Cancer is often associated with a hypercoagulable state and new thrombosis is often the first clinical manifestation of cancer. Surgical treatment of the primary tumor is crucial since it provides the only curative approach in most cases, but management of patients is highly complex, especially in the presence of new antiplatelet drugs and/or anticoagulants. Paraneoplastic syndromes (PNS) represent a frequent complication of renal cell carcinomas (RCC) and include different hematological symptoms in patients, whilst occlusion of arterial blood vessels displays a rare form of PNS accompanying renal tumors. Case presentation We report the case of a 62-year old man who was initially hospitalized due to acute coronary syndrome. He subsequently underwent coronary angioplasty treatment including multiple stenting and treatment with ticagrelor and aspirin. Post-interventional, acute arterial thrombotic emboli of several limb arteries required thrombectomy. By computer tomography we identified a renal lesion suspicious for an RCC and suspected a PNS as underlying cause of the thrombotic complications. Triple anticoagulant therapy was maintained with therapeutic dose low molecular weight heparin (LMWH), aspirin, and clopidogrel, by which we replaced ticagrelor. Surgery was postponed for 4 weeks. We paused LMWH, aspirin and clopidogrel only at the day of surgery and perioperatively restored hemostasis by transfusion of two platelet concentrates. Laparoscopic nephrectomy was uneventful. Pathology confirmed a clear cell RCC. The patient fully recovered whilst slowly reducing anticoagulation dose. Conclusions A multidisciplinary team approach of experts in urology, cardiology and hemostasis was key in managing this patient since a personalized thrombosis consult was needed to minimize the risk of reinfarction due to in-stent thrombosis. We report a therapeutic protocol that may be helpful for the management of similar cases. Furthermore, the finding of thrombotic arterial occlusions in larger blood vessels represents a novel complication of PNS in RCC and adds to the varied possible manifestations of this clinical chameleon.

Introduction Onconeuronal antibodies directed against intracellular antigens are strongly associated with paraneoplastic syndromes and their detection in the absence of cancer is unusual. We herein report a case of anti-Ma2 encephalitis associated with Sjogren's syndrome (SS). Case report An 81-year-old woman followed for a cutaneous lupus with vasculitis associated with SS presented a flare of her disease with neurological worsening including walking difficulty, hypersialorrhea and dysphagia. A paraneoplastic origin of the symptoms was suspected and anti-Ma2 antibodies were positive in serum. The search for an underlying neoplasia was negative. The diagnosis of anti-Ma2 encephalitis secondary to a SS was made. In the literature, the association of anti-Ma2 encephalitis and SS has been previously reported twice. Cases of patients with other onconeuronal antibodies associated with SS have been also reported. Anti-Ma2 encephalitis is a rare condition with a wide spectrum of symptoms associated with a cancer in more than 90% of the cases. Anti-Ma2 encephalitis has also been described after the use of immune check points inhibitors underscoring the role of autoimmunity in its pathogenesis. Conclusion Anti-Ma2 encephalitis is essentially associated with neoplasia but can occur in Sjogren's syndrome.

Introduction: Owing to the poor prognosis of Ewing's sarcoma, reliable prognostic biomarkers are highly warranted for clinical diagnosis of the disease. Materials and Methods: A combination of the weighted correlation network analysis and differentially expression analysis was used for initial screening; glycolysis-related genes were extracted and subjected to univariate Cox, LASSO regression, and multivariate Cox analyses to construct prognostic models. The immune cell composition of each sample was analysed using CIBERSORT software. Immunohistochemical analysis was performed for assessing the differential expression of modelled genes in Ewing's sarcoma and paraneoplastic tissues. Results: A logistic regression model constructed for the prognosis of Ewing's sarcoma exhibited that the patient survival rate in the high-risk group is much lower than in the low-risk group. CIBERSORT analysis exhibited a strong correlation of Ewing's sarcoma with naive B cells, CD8+ T cells, activated NK cells, and M0 macrophages (P < 0.05). Immunohistochemical analysis confirmed the study findings. Conclusions: GLCE and TPI1 can be used as prognostic biomarkers to predict the prognosis of Ewing's sarcoma, and a close association of Ewing's sarcoma with naive B cells, CD8+ T cells, activated NK cells, and M0 macrophages provides a novel approach to the disease immunotherapy.

Objective. Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by chronic hypophosphatemia and osteomalacia. We present case of a patient with a protracted clinical course of TIO. TIO profoundly affected every aspect of his life with subsequent profound physical and psychosocial disabilities. Method. The review of a complex clinical presentation, serial laboratory investigations, and imaging modalities of a patient with TIO caused by a mesenchymal tumor. Results. The patient presented with chronic lower back pain, severe bilateral leg weakness, and multiple pathological fractures due to severe osteoporosis. His investigations revealed hypophosphatemia, low 1,25 dihydroxyvitamin D, phosphaturia and normal serum calcium, and parathyroid hormone. Elevated fibroblast growth factor 23 (FGF23) confirmed the diagnosis of TIO and 68Ga-DOTATATE-positron emission tomography/computed tomography (PET/CT) imaging correctly identified a tumor in the left femoral head. His clinical features and biochemical abnormalities promptly recovered after successful surgical resection of the mesenchymal tumor. Conclusion. The present case demonstrated the need to extensively investigate causes of generalized bone pain in patients with hypophosphatemia, as TIO is highly curable. Importantly, 68Ga-DOTATATE PET/CT imaging successfully identified the FGF23 producing tumor, which was undetectable by conventional imaging, favoring its early use in suspected TIO presentation. The present report highlights the importance of timely diagnosis of this complex medical condition, aiming to improve general awareness and enable better clinical outcomes for this rare disorder.

Background Myasthenia gravis (MG) can occur as a paraneoplastic phenomenon associated with thymoma. The association of MG with renal cell carcinoma (RCC) is not clear. Herein, we describe six cases of MG associated with RCC. Methods There were 283 patients diagnosed with MG admitted to our hospital from 2014 to 2019. Among them, 6 patients also had RCC. None of them had immune checkpoint inhibitor therapies. We performed a retrospective clinical data collection and follow-up studies of these 6 patients. Results These 6 patients with an average MG onset age of 61.3 ± 13.3 years, were all positive for anti-acetylcholine receptor antibodies. MG symptoms appeared after RCC resection in 3 cases. RCC was discovered after the onset of MG in 2 cases, and synchronously with MG in 1 case. After nephrectomy, the MG symptoms showed a stable complete remission in 1 case. Among them, four patients met the diagnostic criteria of possible paraneoplastic neurological syndromes. Conclusions Except for thymoma, patients with MG should pay attention to other tumors including RCC. MG may be a paraneoplastic syndrome of RCC, and further studies are needed to elucidate the relationship.

Contracturing granulomatous myositis (CGM) is a very rare myopathic syndrome where patients present with slowly progressive muscle pain or weakness affecting mainly proximal muscles together with flexion contractures of the limbs. To date, there have only been several case reports of CGM, which have been reported to occur most commonly in association with sarcoidosis. We report a case of CGM associated with recurrent malignant thymoma and myasthenia gravis (MG). A gentleman with history of treated malignant thymoma presented with new onset proximal muscle weakness and pain that later evolved into contractures that persisted despite treatment with steroids and intravenous immunoglobulin. A malignancy workup revealed recurrence of his malignant thymoma warranting chemotherapy treatment. His contractures only resolved after addition of chemotherapy treatment. He later developed clinical features of MG 1 year after his initial elevation in Anti-acetylcholine (Anti-AChR) antibody levels. We postulate CGM to be a paraneoplastic phenomenon of underlying malignant thymoma. Treatment of thymoma together with immunosuppressive therapies led to clinical improvement of our patient’s CGM. The sole elevation of Anti-AChR levels without the accompanying clinical features does not equate to a MG diagnosis, but should raise the clinician’s vigilance for future development of the condition.

Vanishing bile duct syndrome is a rare paraneoplastic syndrome occasionally seen in pediatric Hodgkin lymphoma. It is usually regarded as a fatal disorder. Here, we present a case of vanishing bile duct syndrome cholestasis related to Hodgkin lymphoma that resolved after chemotherapy and radiation.

This work aimed to report the demographic and clinical characteristics of two new cases with non-paraneoplastic anti-Hu-associated gut motility impairment, and perform a thorough revision covering anti-Hu-associated paraneoplastic (PGID) and non-paraneoplastic (nPGID) gastrointestinal dysmotility. Several case series have clearly established a relationship between certain type of cancers, the development of circulating anti-Hu antibodies, and the concomitant usually severe gastrointestinal dysmotility; in contrast, a few studies focused on anti-Hu-associated nPGID. We searched for studies regarding anti-Hu-associated gastrointestinal manifestations and extracted data concerning clinical characteristics of patients, including specific demographic, oncological, neurological, gastrointestinal, histological, and treatment response features. Forty-nine articles with a total of 59 cases of anti-Hu-associated gastrointestinal dysmotility were analyzed. The patients’ age at symptom onset significantly differed between PGID and nPGID (median 61 vs 31 years, p

Patients with cancer may experience neuropathy at any stage of malignancy, ranging from symptoms that are the earliest signs of cancer to side effects of treatment. Peripheral nerves are affected most commonly in a symmetric, stocking-glove pattern. Sensory neuronopathies, plexopathies, and radiculopathies may also be seen. The most common type of neuropathy in patients with cancer is related to chemotherapy, and recently peripheral nerve complications have been described as an effect of immune checkpoint inhibitors too. Other causes include paraneoplastic syndromes, direct tumor infiltration, and radiation. Treatment focuses on addressing the underlying cancer and management of neuropathic pain.

Neoplastic meningitis (NM) and paraneoplastic syndromes (PNSs) are a rare group of disorders present in patients with cancer. Clinical diagnosis of these conditions is challenging, and imaging and laboratory analysis play a significant role in diagnosing. Diagnosis of NM largely depends on documenting circulating tumor cells in the cerebrospinal fluid (CSF) and/or leptomeningeal and nodular enhancement on contrast-enhanced MR imaging of the brain or axial spine. PNSs encompass a variety of symptoms or syndromes. Paraneoplastic neuronal disorder diagnosis requires a multidimensional approach, high clinical suspicion, CSF and serum examination, and imaging. Neuroimaging is an integral part in the evaluation.

The cutaneous paraneoplastic syndromes are rare and intrinsically devoid of any neoplastic nature. The manifestations on the skin and the nails are due to various mechanisms caused by the tumor, either due to production of bioactive substances or in response to it. These disorders evolve in parallel to the malignancy, in that, they regress when the tumor is removed and reappear in the case of tumor recurrence. The aim of this article is to aid with the early recognition of the signs, leading to the early detection of cancer and therefore to better clinical outcomes for the patients.

Non-glandular squamous cell carcinoma (NGSCC) is an extremely rare tumor in Tg.raH2 mice. There have been 5 NGSCC in 1615 control male mice (0.31%) and 2 NGSCC in 1560 control female mice (0.13%) on 26-week carcinogenicity studies, with a range of 0 to 1 of per group per sex in each study without statistical significance in 52 male and 51 female studies conducted in Tg.rasH2 mice. Every case of NGSCC was accompanied by profound granulocytosis.

The patient was a 75-year-old man who developed polyopia and exophthalmos. Chest computed tomography (CT) revealed a mass in the left upper lobe. A CT-guided biopsy suggested lung adenocarcinoma. He was treated by neoadjuvant chemotherapy followed by left upper lobectomy. He was diagnosed with stage IIB pleomorphic carcinoma postoperatively. Preoperative head magnetic resonance imaging revealed exophthalmos and bilateral swelling of the extraocular muscles. The thyroid function of the patient was within the normal range, and he tested negative for autoantibodies. As his symptoms and swelling of the extraocular muscles improved postoperatively, he was diagnosed with paraneoplastic syndrome.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by factor-induced dysregulation of phosphate and vitamin D metabolism resulting in alterations in bone formation, leading to bone pain and fractures. While the true incidence is likely underestimated, less than 500 cases of TIO have been reported since initial description in 1947. TIO cases have classically been associated with mesenchymal tumors of bone and soft tissue, but have also rarely been linked to malignant tumors, with scant reports implicating non-mesenchymal tumors. TIO is mediated through inappropriate tumor overproduction of fibroblast growth factor 23 (FGF23). Increased FGF23 secretion leads to hypophosphatemia by (1) reduced phosphate reabsorption via activation of the proximal renal tubular epithelial cells to internalize sodium phosphate cotransporters and (2) reduced activation of vitamin D3 via inhibition of the renal enzyme 1-α hydroxylase. Low circulating levels of active vitamin D lead to reduced intestinal phosphate absorption and impaired mineralization of osteoid matrix. TIO in breast cancer poses a distinct diagnostic challenge due to the common adjunct oncologic management with bone protection therapy such as denosumab or bisphosphonates. These agents can be culprits of hypophosphatemia and hypocalcemia, rendering timely diagnosis of TIO difficult. Delay of diagnosis of TIO can result in worsening functional status, and early morbidity and mortality. To date, there has been one prior case report of TIO in breast cancer, and herein we describe two additional cases of TIO in this setting.

The tumors that induce autoimmune hemolytic anemia (AIHA) are usually hematological neoplasms such as malignant lymphoma and chronic lymphocytic leukemia. AIHA associated with germ cell tumors is very rare with literature limited to case reports with most of them reported with ovarian dermoid, which abated with the removal of the tumor. We report an unusual presentation of AIHA with malignant sacrococcygeal germ cell tumor in a 3-year-old child, which rapidly disappeared after the excision of a sacrococcygeal teratoma.

A 74-year-old woman with a history of suspected tumor-induced osteomalacia underwent 99mTc-HYNIC-TOC scintigraphy to search potential culprit tumor. The images showed one in the middle shaft of left femur without corresponding morphology change on the CT portion of the subsequent SPECT/CT images. The patient declined surgical exploration of the left femur. Another activity was in the right breast, which was resected and pathologically confirmed as breast carcinoma. Postsurgically, the patient's symptoms were not improved. Four years later, a repeat 99mTc-HYNIC-TOC scintigraphy showed more prominent activity in the left femur with gross abnormality on the corresponding CT images.

METHODS Seventy-six patients who had surgically removed tumors that caused osteomalacia were included in this retrospective investigation. All patients underwent both 18F-FDG and 68Ga-DOTATATE PET/CT prior to surgery. The prognostic value of presurgical FDG PET/CT study was determined with 5-year follow-up. RESULTS In the presurgical evaluation, 68Ga-DOTATATE detected lesions in all 76 patients. However, FDG PET/CT was positive in only 25 among all 76 patients. Following surgical removal of the causative tumor, all 76 patients had symptomatic relief and normalization of the serum phosphate level initially. However, 15 of 76 cases (19.7%) had recurrent hypophosphatemia and became symptomatic again during the follow-up. Among these 15 patients with recurrence, 11 (73.3%) had recurrent lesions at the original location of the resected causative tumors, whereas 4 were in other locations due to malignant nature of the primary tumor. Interestingly, 14 of these 15 patients with recurrent disease had positive presurgical FDG PET/CT findings with an incident ratio of 56.0% (14 of 25). In contrast, only 1 patient with recurrent disease had negative presurgical FDG PET/CT scan with an incident ratio of 1.9% (1 of 51), significantly less than the positive presurgical FDG PET/CT group (P < 0.05). CONCLUSIONS A positive presurgical FDG PET/CT suggests increased likelihood for possible recurrence of TIO after surgical resection. In contrast, when a causative tumor detected by 68Ga-DOTATATE PET/CT does not have elevated activity on FDG PET/CT, the chance of recurrence is very small.

Subacute cutaneous lupus erythematosus (SCLE) is a subtype of cutaneous lupus erythematosus characterized by high photosensitivity, the occurrence of annular or papulosquamous skin lesions located in body regions exposed to UV light, the presence of anti-Ro/SS‑A antibodies, and mild systemic involvement, such as arthralgia and myalgia. Similar to other subtypes of cutaneous lupus erythematosus, certain trigger factors exist for the development of SCLE, such as exposure to UV light, cigarette smoking and drugs. Rheumatic diseases, such as dermatomyositis, have been known as paraneoplastic syndromes for a long time. In recent years, there has been an accumulation of publications on the association of SCLE with malignant diseases. This article reports the case of a 78-year-old female patient who was diagnosed with the concomitant development of SCLE and gastric carcinoma. In all older patients with SCLE, patients with widespread skin affection outside the UV-exposed body areas or patients with B‑symptoms, the presence of a paraneoplastic SCLE should be considered and appropriate diagnostic steps should be initiated to screen for an associated neoplastic disease.Der subakut kutane Lupus erythematodes (SCLE) ist ein Subtyp des kutanen Lupus erythematodes, der sich durch hohe Photosensitivität, Auftreten von anulären oder papulosquamösen Hautveränderungen im Bereich der UV-exponierten Körperregionen, serologischen Nachweis von Anti-Ro/SS-A-Antikörpern und milde systemische Beteiligung wie Arthralgien und Myalgien auszeichnet. Wie bei anderen Formen des kutanen Lupus erythematodes kann auch der SCLE durch bestimmte Triggerfaktoren wie UV-Exposition, Zigarettenrauchen oder Medikamente ausgelöst werden. Rheumatische Erkrankungen wie die Dermatomyositis sind seit Langem als paraneoplastische Syndrome bekannt. In den letzten Jahren wird zunehmend über die Assoziation von SCLE und Tumorerkrankungen publiziert. Wir berichten den Fall einer 78-jährigen Patientin, bei der zeitgleich mit der Entwicklung eines SCLE ein Magenkarzinom diagnostiziert wurde. Bei SCLE-Patienten höheren Alters, ausgedehntem Befall außerhalb der UV-exponierten Körperpartien oder neu aufgetretener B‑Symptomatik sollte das Vorliegen eines paraneoplastischen SCLE in Erwägung gezogen und entsprechende diagnostische Schritte zur Abklärung einer Tumorerkrankung sollten eingeleitet werden.

Neurological paraneoplastic syndromes are exceedingly rare, and often difficult to recognize clinically. Paraneoplastic achalasia is a condition characterized by new-onset dysphagia that is unrelated to tumor burden, most often due to the development of auto-immune antibodies targeting esophageal tissue. Due to the rarity of this condition, diagnosis is often delayed, leading to increased time to treatment. Here we report a case of a rare paraneoplastic achalasia in a female child with EBV + Hodgkin lymphoma (HL), review literature describing paraneoplastic achalasia, and discuss treatment strategies for improving clinical outcome in these patients.

Paraneoplastic neurologic diseases (PND) are rare but can occur in patients with common malignancies including breast cancer. In patients with hormone receptor (HR)-negative human epidermal growth factor receptor 2 (HER2)-positive breast cancer, PND have been reported in association with anti-Yo antibodies and with clinical presentation of paraneoplastic cerebellar degeneration. We describe the case of a woman with progressively altered mental status and seizures, ultimately requiring admission. Based on her clinical presentation, imaging findings, and evidence of neural-directed antibodies in her serum and cerebrospinal fluid, she was diagnosed with paraneoplastic limbic encephalitis (LE) due to an underlying HR-negative, HER2-positive breast cancer. She showed a transient response to immunosuppression but had more significant improvement after surgical resection and initiation of chemotherapy along with HER2-directed therapy. To the best of our knowledge, this is the first documented case of paraneoplastic LE in a patient with HR-negative, HER2-positive breast cancer likely caused by the production of an unclassified anti-neuronal antibody.

A 30-year-old man was admitted to our hospital because of pain in his proximal extremities. The pain mimicked polymyalgia rheumatica (PMR) and it temporarily improved by a low dose of glucocorticoids, but his symptoms relapsed many times. After six years of glucocorticoid treatment, he developed abdominal pain and ascites, for which he was diagnosed with malignant peritoneal mesothelioma (MPM). His PMR-like symptoms improved with cytoreductive surgery and chemotherapy for MPM. Finally, we diagnosed this PMR-like syndrome to be paraneoplastic syndrome with MPM. Although cases of MPM complicated by PMR-like syndrome are rare, MPM should be taken into account in the differential diagnosis.

Paraneoplastic pemphigus (PNP) is a severe autoimmune syndrome commonly triggered by neoplasms. The prognosis of CLL-associated PNP is dismal due to its refractory course and secondary infection and no standard treatment was recommended. We retrospectively reported six CLL with PNP cases from 842 cases of CLL including diagnosis, treatment and prognosis. The median time between the initial of CLL to PNP was 36 months while the median overall survival from the diagnosis of PNP was 26 months. And three cases died of lung infection while 5 developed pulmonary symptoms. And 5 cases received fludarabine-based chemotherapy before developing PNP, which suggesting fludarabine was one of potential causes of PNP. For the treatment, five patients were rescued by combined regimens including rituximab, methylprednisolone, immunoglobulin, fresh frozen plasma and the last received ibrutinib combined with short-term prednisone. Fludarabine-based regimen may be one of the potential causes of PNP. The combined regimen might shed a new light, while ibrutinib is a promising drug for CLL with PNP, but needs much more evidence. PNP should be carefully treated to guide early diagnosis and intervention for a better prognosis.

The severity of the poststreptococcal acute glomerulonephritis is considered to be modulated by the immune response of each individual, although there had been few reports regarding specific factors. Renal cell carcinoma is a cancer frequently associated with paraneoplastic syndrome, characterized by fever, leukocytosis, elevated cytokines, and elevated hormone levels. All of these symptoms resolve after tumor resection. A girl with renal cell carcinoma developed renal failure rapidly, which resolved promptly right after nephrectomy for the carcinoma. She was diagnosed as having poststreptococcal acute glomerulonephritis according to the results of pathological and serological examinations. In addition, elevated serum interleukin-6 level before the surgery was detected. Six and a half years after the diagnosis, the patient's renal function was within normal range and she was tumor free. Because of the quick resolution of her renal dysfunction after the nephrectomy, paraneoplastic syndrome induced by renal cell carcinoma seemed to play a key role in the accentuation of poststreptococcal acute glomerulonephritis.

Background Tumor-induced osteomalacia (TIO) is often misdiagnosed as hypophosphatemia that is not valued. The aim of this study was to analyze the diagnostic value of 68Ga-DOTA-TATE PET/CT imaging for TIO. Methods Clinical data was retrospectively collected for 56 patients with suspected TIO at the Affiliated Hospital of Southwest Medical University between January 2016 and December 2019, where patients were examined by 68Ga-DOTA-TATE PET/CT and 99mTc-HYNIC-TOC SPECT. Based on the results of the patient's surgery, the diagnostic efficacy of the two imaging techniques on TIO were analyzed. Results Of the 56 patients, 41 were diagnosed with TIO, with phosphorus levels ranging from 0.25 to 0.75 mmol/L. The remaining 15 patients were non-TIO. Results of 99mTc-HYNIC-TOC SPECT showed 33 cases were positive, with a diagnostic sensitivity, specificity, and accuracy of 58.54%, 86.67%, and 66.07%, respectively. Results of 68Ga-DOTA-TATE PET/CT imaging showed 46 cases were positive, with a diagnostic sensitivity, specificity, and accuracy of 95.13%, 60.00%, 71.43%, respectively. The average tumor size with 68Ga-DOTA-TATE PET/CT imaging was 2.58±1.71 cm. The lesions of 41 patients involved bone and soft tissue, while 18 patients showed osteolytic bone destruction. Distribution was mainly under the skin, followed by intermuscular space, and cortex of bone. Compared with muscle density, the lesions showed uniformly or slightly lower density nodules. Using 99mTc-HYNIC-TOC SPECT, the planar imaging of 30 patients showed that radioactive uptake increased at the early stage, and it can be accurately positioned on the SPECT imaging. Conclusions The 68Ga-DOTA-TATE PET/CT imaging demonstrated high accuracy in the diagnosis of TIO and detected small lesions, which could provide more comprehensive information for clinicians, and provide a reference value for the treatment and prognosis of patients.

Paraneoplastic Pemphigus (PNP), a rare autoimmune blistering disease, can be accompanied by both benign and malignant neoplasms. The most frequently reported associated malignancies include lymphomatoid and hematologic malignancies, Castleman's disease, carcinoma, thymoma. In a patient suspected of PNP, with no known history of malignancy, an extensive workup is suggested to look for underlying malignancy, which has to be treated to induce PNP remission. In this clinical case report, cross sectional imaging of a young female diagnosed with PNP, unveiled a pericardial mass lesion extending into transverse pericardial sinus. Excisional biopsy was performed. Histopathology revealed pericardial ectopic thymoma.

Paraneoplastic syndromes are rare diseases caused by malignancies through means other than mass effect or metastasis. Paraneoplastic phenomena can be the first sign of cancer and can be fatal. Paraneoplastic rheumatic syndromes can occur with hematologic cancers, lymphoproliferative disease, and solid tumors. Diseases that feature an advanced age at onset, significant constitutional upset, inadequate response to treatment, and otherwise atypical characteristics should increase the index of suspicion for a paraneoplastic syndrome.

Background Castleman disease (CD) is a lymphoproliferative B-cell disease that is diagnosed from lymphoid hyperplasia with vascular proliferation. Symptoms may include fever, night sweats, and weight loss. Cutaneous manifestations often may go unnoticed since little has been described in the literature regarding them. Materials and methods A search of CD with cutaneous manifestations was performed in PUBMED, ProQuest, Ovid, Scopus, EMBASE, and Medline. All articles included patients over 18 years of age with a diagnosis of CD and cutaneous manifestations. Results A total of 68 articles were included. The most common cutaneous manifestations include paraneoplastic pemphigus and erythematous-brown plaques, papules, or nodules. Patients presenting with these manifestations should always have a thorough physical exam, and clinicians should try to identify any palpable lymph nodes. A complete workup to rule out other neoplasias needs to be performed as well. Conclusions A better understanding of these skin manifestations of CD may help physicians promptly diagnose and reconsider the path of diagnostic tests to identify this entity.

The search for autoantibodies in patients with acute and chronic neuropathies has become widespread in neurological practice. These tests are more routinely available and therefore are more commonly requested in larger hospitals with neuroscience centres, although they are now also regularly requested from district general hospital settings, including by non-neurologists. However, the clinical value of these frequently expensive tests is often unclear and their impact on management not always obviously beneficial. This article reviews the main immunological tests used to search for specific autoantibodies in the setting of neuropathy and discusses their potential diagnostic importance, together with the eventual therapeutic implications of results obtained.

Dermal paraneoplastic syndromes are non-malignant disorders, caused indirectly by the increase in growth factors or as immunological reactions, which lead to a variety of inflammatory, hyperkeratotic or proliferative skin reactions. They can occur as facultative or obligate paraneoplastic dermatoses, which are associated with oncological processes (solid tumours or hematologic diseases). The recognition of paraneoplastic skin disorders can accelerate proper diagnosis and determine better prognosis for the patient and is also important to clinicians because it is often the first symptom of life-threatening malignancies. Many of them may also cause ocular changes that can lead to serious complications including perforation of the eye bulb, vascular changes in the retina resulting in vision loss and demand multidisciplinary co-operation with an ophthalmologist. This manuscript is a review of the literature about eye disorders in association with dermal paraneoplastic syndromes.

Background Stauffer Syndrome (SS) is a paraneoplastic disorder associated with renal cell carcinoma (RCC). First described by Herbert Maurice Stauffer in 1961, it is characterized by hepatic dysfunction in the absence of metastasis, and elevated alkaline phosphatase, aminotransferases and prolonged prothrombin time. Initial reports did not include jaundice as an inclusion criterion. We aim to report the rare SS jaundice variant in a patient with a small renal mass and review the literature to determine if the size of the renal mass could influence the development of the SS. Case presentation The aim of this article is to present the case of a 53-year-old male with Stauffer syndrome jaundice variant secondary to a 2.5 cm renal mass, treated with laparoscopic radical nephrectomy with complete resolution of the syndrome. Conclusions This syndrome is yet to be fully understood, and as far as the evidence shows, size does not matter. This entity should always be in mind when encountered with a patient with liver dysfunction and jaundice with a suspicion or confirmed diagnosis of a renal mass. To date, and to our knowledge, there have been eleven reported cases of paraneoplastic cholestatic jaundice syndrome including the current case. Six cases presented in patients with small renal mases (

Dermatomyositis belongs to a group of rare autoimmune diseases characterized by a variable degree of skin symptoms and myopathy. The clinically diagnostic hallmarks of dermatomyositis are heliotrope rash, Gottron's papules and weakness of the proximal muscles. Along with pathognomonic, characteristic, and compatible cutaneous features, several uncommon and rare skin manifestations have been reported. In addition, new skin lesions have been described in dermatomyositis patients. Furthermore, rare clinical subtypes of dermatomyositis have been reported in the literature, including Wong-type dermatomyositis, characterised by the coexistence of dermatomyositis and pityriasis rubra pilaris with hyperkeratotic, erythematous, follicular confluent papules on the back of the hands along the bony prominences. In addition, plenty of autoantibody subsets have been recently described that are related to distinct clinical features and systemic involvement, such as anti-MDA5 autoantibodies. We reviewed the English- and German-language scientific literature using the key words "dermatomyositis", "autoantibodies", and "clinical features", alone or in combination, focusing on particular cutaneous symptoms and their association with defined autoantibody profiles. Furthermore, we focused on rare subtypes of dermatomyositis, unusual clinical features, and recently described skin lesions.

Objectives We aimed to describe the clinical and histopathologic features of Castleman disease (CD), particularly emphasizing its associations with paraneoplastic pemphigus (PNP) and prognosis. Methods We retrospectively enrolled 123 CD patients at our center. Clinical, pathologic, and laboratory data were reviewed. Results Fifty percent of the patients had PNP. Compared with those without PNP, patients with PNP-associated CD had more hyaline vascular (HV) variants (83.9% vs 57.4%), fewer mixed cellular variants (16.1% vs 24.6%), and no plasmacytic variants (0% vs 18.0%). Thirty-eight of 87 patients with the HV variant of CD (HV-CD) had stroma-rich (SR) features, and the incidence rate was higher in those with PNP-associated CD than in those without PNP (48.4% vs 13.1%, P < .001). The SR variant was associated with higher PNP-associated IgG titers than SR absence before surgery (median 1:160 vs 1:80, P = .019) or after surgery (median 1:160 vs 1:40, P = .013). The SR variant was also an unfavorable prognostic factor for CD survival in univariate analysis. The 3-year survival rates were 47.5% among those with PNP and 87.7% among those without PNP (P < .001). Conclusions PNP is associated with specific subtypes of CD and affects survival. The SR variant of HV-CD positively correlates with the incidence of PNP.

The literature review considers the fundamental elements of a relationship between cancers and rheumatic diseases, including a variety of paraneoplastic syndromes, a profile of rheumatic diseases associated with the development of oncopathology, and autoimmune rheumatic syndromes detected in patients who receive anticancer therapy. Emphasis is placed on the need for interdisciplinary interaction to deepen understanding of the pathophysiological mechanisms of both groups of diseases and to improve medical care for patients.

To describe our clinical experience with surgical treatments for sinonasal phosphaturic mesenchymal tumors diagnosed at our institution.Retrospective case series.Affiliated Sixth People's Hospital, Shanghai Jiao Tong University.We retrospectively reviewed the medical records of 10 patients diagnosed with phosphaturic mesenchymal tumors associated with tumor-induced osteomalacia between December 2014 and October 2019.There were 4 men and 6 women with a disease course of 1 to 19 years. All patients exhibited hypophosphatemia and tumor-induced osteomalacia. The tumor was located in the sinonasal region, frontal bone, and temporal bone in 8 patients, 1 patient, and 1 patient, respectively. Technetium-99m octreotide scintigraphy was used for tumor localization in 4 cases. Six patients underwent endoscopic resection; the remaining 4 underwent unilateral transorbital anterior and posterior ethmoid artery ligation + endoscopic resection, endoscopic resection + skull base repair, internal carotid artery stenting + transcatheter arterial embolization + temporal bone tumor excision + adipose tissue plugging, and endoscopic resection + transfrontal craniotomy (n = 1 each). Two patients had a history of incomplete endoscopic resection. All patients achieved clinical remission and normalized biochemical indices after surgery. Only 1 patient developed recurrence and died of a brain hernia.A diagnosis of sinonasal phosphaturic mesenchymal tumors should be based on a combination of clinical, imaging, and pathological findings. Technetium-99m octreotide scintigraphy helps in locating the tumor. Complete surgical excision guarantees clinical remission, and preoperative transcatheter arterial embolization or feeding artery ligation may reduce intraoperative bleeding in cases of highly vascularized tumors.