Paraneoplastic Manifestation Research Articles

Paraneoplastic Polymyositis in a Patient of Myelofibrosis

Polymyositis is a rare rheumatologic disorder. Exact cause is unknown but autoimmunity, genetic and environmental factors like infection and drugs may be responsible. It may be a primary autoimmune disease, associated with other autoimmune diseases or underlying malignancy. There is two-way relationship between polymyositis and malignancy. Patients with polymyositis and dermatomyositis has increased chance of various malignancies. On the other hand polymyositis and dermatomyositis may be a paraneoplastic manifestation of some malignancies like carcinoma lung, ovary, breast, pancreas, colon, lymphoma, MDS and myeloproliferative disorders. We have diagnosed a case of polymyositis in a patient of Myelofibrosis (MF). The patient presented with inflammatory myopathy affecting proximal muscles of the limbs, neck muscles, laryngeal and pharyngeal muscles. Muscle enzymes were markedly elevated, EMG and MRI were in favour of inflammatory myopathy. Muscle biopsy showed inflammatory infiltrates in muscles mostly by T- cells with myonecrosis, degeneration and regeneration without vasculopathy and perivascular change. Primary polymyositis and other autoimmune diseases were excluded by absence of relevant autoantibodies. So he was diagnosed as a case of paraneoplastic polymyositis.
 Journal of Armed Forces Medical College Bangladesh Vol.15 (1) 2019: 116-118

Necrotising migratory erythema leading to the diagnosis of a metastatic glucagonoma without diabetes

A case of necrotising migratory erythema (NME), which is one of the distinctive paraneoplastic skin manifestations associated with the glucagonoma syndrome, is described and discussed. In 80% of al...

Paraneoplastic Confusion: A Case of Anti-Hu Encephalitis

Paraneoplastic manifestations are frequently seen in patients with small cell lung carcinoma (SCLC) and can present as diverse clinical entities ranging from endocrinopathies to neurological conditions. Anti-Hu encephalitis is a rare paraneoplastic manifestation most commonly seen in patients with SCLC. This case highlights an SCLC patient who presented with behavioral changes, cognitive deficits, and memory issues, and was found to have anti-Hu encephalitis. The subacute course of this clinical entity should be kept in mind and prompt further investigation in SCLC patients with these symptoms, especially when the laboratory workup of the major culprits is negative or inconclusive.

Tumorerkrankungen an der Haut erkennen – paraneoplastische Hauterkrankungen

Skin diseases represent the second most common paraneoplastic manifestations after endocrine disorders. Paraneoplastic dermatoses may arise as the first clinical sign of occult malignancies, or manifest during the course of apreviously diagnosed neoplasm. Dermatoses belonging to the group of obligate paraneoplastic syndromes manifest only in the presence of underlying malignancies. Other skin diseases may be associated with malignancy in asubset of patients.

Autoimmunity, Clonal Hematopoiesis, and Myeloid Neoplasms.

Clonal hematopoiesis has been linked with the development of hematologic malignancy and atherosclerotic cardiovascular disease; however, the association with autoimmune diseases remains to be defined. The link between autoimmune diseases and myeloid neoplasms (MNs) is complex, often multifactorial, and seems bidirectional. The limited data suggest an increased risk of MNs in rheumatoid arthritis and systemic lupus erythematosus. Paraneoplastic manifestations of MN include arthritis, vasculitis, and connective tissue disease. Treatment options for autoimmune disease such as cyclophosphamide and azathioprine have been associated with MNs, whereas the data for methotrexate and tumor necrosis factor inhibitors are equivocal.

Immunological Bases of Paraneoplastic Cerebellar Degeneration and Therapeutic Implications.

Paraneoplastic cerebellar degeneration (PCD) is a rare immune-mediated disease that develops mostly in the setting of neoplasia and offers a unique prospect to explore the interplay between tumor immunity and autoimmunity. In PCD, the deleterious adaptive immune response targets self-antigens aberrantly expressed by tumor cells, mostly gynecological cancers, and physiologically expressed by the Purkinje neurons of the cerebellum. Highly specific anti-neuronal antibodies in the serum and cerebrospinal fluid represent key diagnostic biomarkers of PCD. Some anti-neuronal antibodies such as anti-Yo autoantibodies (recognizing the CDR2/CDR2L proteins) are only associated with PCD. Other anti-neuronal antibodies, such as anti-Hu, anti-Ri, and anti-Ma2, are detected in patients with PCD or other types of paraneoplastic neurological manifestations. Importantly, these autoantibodies cannot transfer disease and evidence for a pathogenic role of autoreactive T cells is accumulating. However, the precise mechanisms responsible for disruption of self-tolerance to neuronal self-antigens in the cancer setting and the pathways involved in pathogenesis within the cerebellum remain to be fully deciphered. Although the occurrence of PCD is rare, the risk for such severe complication may increase with wider use of cancer immunotherapy, notably immune checkpoint blockade. Here, we review recent literature pertaining to the pathophysiology of PCD and propose an immune scheme underlying this disabling disease. Additionally, based on observations from patients' samples and on the pre-clinical model we recently developed, we discuss potential therapeutic strategies that could blunt this cerebellum-specific autoimmune disease.

Precocious pseudopuberty, a paraneoplastic manifestation: a report of 2 cases

Peripheral precocious puberty (PPP) may be a paraneoplastic manifestation, associated with beta human chorionic gonadotropin (β-hCG)-secreting tumors. We describe 2 young children with β-hCG-secreting tumors presenting with signs of pubertal activation. In the first patient, a 16-month-old boy with hepatoblastoma, only initial signs of PPP at presentation were identifiable, with concomitant high levels of β-hCG. Although the tumor had good response to therapy, β-hCG levels were fluctuant until the tumor was resected surgically. The second patient, an 18-month-old boy with intracranial germ cell tumor, presented with clear signs of pubertal activation and genitalia enlargement with no initial alteration of sex hormones. In both cases, the oncologic response to therapy was good. In the first case, full remission of the pubertal signs was observed; in the second, pubertal signs were still visible 20 months after the end of treatment.

Investigation of immune repertoires in thymoma.

e21117 Background: Paraneoplastic autoimmune manifestations are seen in 30 to 40% of thymoma cases. Thymus plays the main role in T- cell maturation with ‘negative selection’ of autoreactive T-cells. Due to reasons not well understood, this function is deranged in thymomas resulting in dysregulation of immune function, loss of ‘self-tolerance’ and autoreactivity. The low cost and high-throughput of next generation sequencing techniques now make it feasible to analyze extensive T-cell receptor(TCR) gene rearrangements in peripheral blood lymphocytes. Methods: 40 patients with thymoma were identified between December, 2010 and September, 2019 at Indiana University. Whole blood samples were collected after diagnosis of thymoma but prior to thymectomy. 20 patients developed paraneoplastic manifestations at some point during the disease course. Genomic DNA was isolated from whole blood samples and TCR analysis performed using a commercially available next generation sequencing assay. This was compared with the control population of 20 patients who did not demonstrate any paraneoplastic features during their disease course. Patients were matched based on age, clinical stage and WHO classification. Results: Paraneoplastic manifestations seen in the 20 patients included Myasthenia Gravis (n = 12), Good’s Syndrome (n = 2), immune mediated cytopenia (n = 3) including pure red cell aplasia, pure white cell aplasia and thrombocytopenia, neurologic manifestations such as encephalitis (n = 2), Autoimmune Autonomic Neuronopathy(n = 1) and Isaac’s Syndrome (n = 2). Some patients also demonstrated more than one paraneoplastic syndrome. The onset and course of these manifestations varied; onset prior to diagnosis of thymoma, onset after thymectomy and improving or worsening clinical features after thymectomy. Since the exact mechanism of autoimmunity is still unknown, we attempted to detect differences in TCR subsets between these two groups. Our study shows that it is technically feasible to interrogate the peripheral blood lymphocytes of thymoma patients for TCR gene clonality and diversity. Conclusions: Diverse autoimmune syndromes can be described in thymoma patients with varying clinical course and severity. Although our study is underpowered, TCR gene sequencing is efficient and may not only improve our understanding of these paraneoplastic syndromes but also identify biomarkers for their diagnosis. Our research could also potentially lead to development of targeted treatment options in the future based on TCR manipulation.

Eosinophilic colitis in cancer patients.

e16500 Background: Eosinophilic colitis (EoC) is a rare form of eosinophilic gastrointestinal disease characterized by diffuse eosinophilic infiltration in the deep lamina propria and extensive crypt epithelial injury with apoptosis and crypt abscesses. The pathophysiology is still unclear and associated with many etiologies. We described the clinical characteristics of EoC in cancer patients. Methods: We retrospectively reviewed the pathology report of the colonic samples from endoscopy or surgical resection obtained between 01/2000 and 12/2018 at MD Anderson Cancer Center. The included cases had significant eosinophilia with key word description of “numerous”, “many” or “dominant” on the pathology. Clinical data were collected and analyzed. Results: A total of 41 cases were included based on the inclusion criteria with 34% men, with a median age of 60. 27% had NSAID use and 40% were smokers. One-fourth had co-existing autoimmune conditions. 78% had cancer diagnosis (hematologic at 41%, followed by genitourinary and gastrointestinal origin) with the rest carrying no cancer diagnosis. Half of the cases received chemotherapy with median duration of 180 days between chemotherapy to EoC onset. Common EoC symptoms included diarrhea, and abdominal pain which were present in 76% patients. Diarrhea was more prevalent in patients who received chemotherapy (85% vs 42%). Median duration of EoC symptoms was shorter in cancer patients (240 vs 30 days) and chemotherapy exposure (120 vs 30 days). Hospitalization for EoC was required in 15% cases. Most commonly administered treatment for EoC was immunosuppressants (22%). Normal colonoscopy was reported in 88% patients at the time of EoC diagnosis. All-cause mortality was 37% and was mostly related to underlying malignancy. Conclusions: The disease course of EoC in cancer patients on chemotherapy is not well defined. It appeared to be less severe than non-cancer patients, which raised the possibility of two separate subclasses of this disease entity. Cancer/chemotherapy related EoC could be a GI specific paraneoplastic manifestation, and behave differently from other etiology. [Table: see text]

Idiopathic Hypercalcemia in Decompensated Cirrhosis: Reexploring an Entity in Oblivion

Hypercalcemia is a rare metabolic abnormality seen in patients with cirrhosis and is usually considered a paraneoplastic manifestation of hepatocellular carcinoma. Idiopathic hypercalcemia in cirrhosis is a diagnosis of exclusion, which is considered when all the causes of hypercalcemia have been ruled out. Here, we report a rare case of idiopathic hypercalcemia presenting as acute kidney injury in a case of decompensated cirrhosis, managed with adequate hydration and injection of ibandronate and intranasal calcitonin, leading to the normalization of serum calcium and resolution of acute kidney injury.

SAT-LB23 Paraneoplastic Hypercalcemia in a PTH Producing Adrenocortical Carcinoma - a Rare and Deadly Condition

Background: Hypercalcemia is a commonly encountered paraneoplastic manifestation of certain cancers with or without endocrine differentiation. However, the association between adrenocortical carcinoma (ACC) with paraneoplastic hypercalcemia is very rare, and therefore little is known about the cause and its relevance in the disease. Clinical Case: A 40-year-old woman presented in the hospital with a 5-month history of progressive flank pain with unintentional weight loss of 6 kg. MRI revealed a mass of 9x8.1x4.8 cm of the right adrenal gland with inhomogeneous contrast enhancement. Biochemical investigations provided evidence of endogenous hypercortisolism (24-hour urinary cortisol excretion [490 µg, n<236 µg/l], 1mg dexamethasone suppression test [199 nmol/l, n<50 nmol/l], ACTH [28 ng/l, n<61 ng/l]) although the patient did not show any specific clinical sign of overt hypercortisolism. In addition, laboratory testing revealed an exceptionally high plasma level of calcium [max 3.67 mmol/l (albumin-corrected)] and low phosphate [min 0.26 mmol/l] in the setting of low PTH [6.4 ng/l, n>15 ng/l] and PTHrP levels [<0.50 pmol/l]. However, subsequent dilution unmasked a highly elevated PTH concentration of 2171.5 ng/l with persistent low PTHrP levels, indicating false low values due to a hook effect in the initial measurement. Levels of 1,25-dihydroxy vitamin D and 25-hydroxy vitamin D were in the normal range. A PET-CT provided no indications of metabolically active (osseous) metastases. After correction of the serum calcium towards tolerable values, the tumor was removed by open en bloc adrenalectomy. Histologic evaluation confirmed an ACC (TNM pT4 pN1 (2/3), L1, V1, high grade) despite missing immunohistochemically expression of classical adrenal markers (diagnosis of exclusion). Supplemental quantitative RT-PCR studies support the diagnosis of ACC by detecting significant SF-1 and CYP11B2 expression in the tumor cells. Further analyses provided evidence that the mRNA expression of PTH, but not PTHrP, was moderately increased in the ACC sample compared to NCI H295R cells. Upon tumor resection, serum calcium levels swiftly normalized indicating the tumor as the sole source of PTH secretion. Despite initiation of adjuvant mitotane- and salvage chemo-therapy, the patient died 3 months later upon of a massive tumor relapse with a recurrence of severe hypercalcemia. Conclusion: This case demonstrates paraneoplastic hypercalcemia in a PTH producing ACC. PTH may induce hypercalcemia, impair adrenal steroid synthesis and act as an autocrine growth factor in ACC, as described in few individual cases for PTHrp producing ACC [1]. This suggests a poor prognosis for this rare entity.1. Rizk-Rabin, M., et al., Differential Expression of Parathyroid Hormone-Related Protein in Adrenocortical Tumors: Autocrine/Paracrine Effects on the Growth and Signaling Pathways in H295R Cells. 2008.

Malignant Hypertension Secondary to Renin-Producing Hepatoblastoma

AbstractClinical presentation of hepatoblastoma is often insidious and its paraneoplastic manifestations are not uncommon. We report an extremely rare case of a renin-secreting hepatoblastoma inducing malignant hypertension remarked in our clinic. The hepatic malignancy classified as PRETEXT IV and a multidisciplinary approach according to SIOPEL III was made with a poor outcome. Hepatoblastoma in children should be considered as possible etiology of hypertension in children.

Screening for Cancer in Patients with Glomerular Diseases.

The diagnosis of malignancy in the setting of nephrotic syndrome is associated with a poor overall and kidney survival regardless of whether the glomerular disease represents a paraneoplastic manifestation or the cancer is a coincidental finding. The diagnosis of the neoplasia leads to consideration

A case of juvenile lupus with an extremely rare dendritic cell malignancy: Interdigitating dendritic cell sarcoma – coexistence or paraneoplastic manifestation?

Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease, characterized by circulating autoantibodies, widespread inflammation, and tissue destruction. The association between cancer and SLE is intriguing in view of their common pathophysiological pathways. It is established that there is an increased risk for overall malignancies in SLE, with standardized incidence ratios ranging from 1.14 to 3.6. Hematological malignancies are more common than solid organ malignancies in SLE. Malignancy when associated with lupus usually follows the diagnosis, but can occur concurrently or even predate the diagnosis of SLE. Neoplasms of dendritic cells (DCs), the key antigen-presenting cells, are rare, and they account for

Fibrolamellar hepatocellular carcinoma with paraneoplastic neuropsychiatric manifestations.

Fibrolamellar hepatocellular carcinoma with paraneoplastic neuropsychiatric manifestations.

Hypertrophic osteoarthropathy as a paraneoplastic manifestation of lung cancer.

Hypertrophic osteoarthropathy (HOA) is a syndrome that consists of periostitis, digital clubbing, and painful polyarthropathy. The management and prognosis of HOA is dependent on the underlying disease process. Recognising and treating it accordingly will reduce the symptom burden of patients. We present a case of a patient diagnosed with non-small cell lung cancer and HOA suffering from severe pain, and review specific therapies for the management of HOA-related pain.

Solving up the jigsaw puzzle: Necrolytic Migratory Erythema Associated with Multifocal Neuroendocrine Tumor of Pancreas, A case report.

Introduction: Necrolytic migratory erythema (NME) is a disorder that is recognized by reddish, migrating areas of blistering that heal with pigmentation. It is a characteristic rash that is often recognized by its distinct appearance and history. It has strong association with glucagonoma, a pancreatic neuroendocrine tumor arising from the alpha type islet cells. In such cases NME presents as a paraneoplastic manifestation of the disease. The diagnosis of this rare tumor depends on high index of suspicion on the basis of history and examination and relevant pathological and radiological investigations. This tumor is potentially curable by surgery. Case Presentation: In this article the authors describe a 36 years old female patient with NME and a multifocal pancreatic neuroendocrine tumor with clinical features of glucagonoma syndrome. After investigations she underwent total pancreatectomy and within a few days her skin lesions and clinical symptoms started improving. Conclusion: Prompt diagnosis and management are of paramount importance in the management of glucagonoma. It is possible if there is high index of suspicion and the management is done appropriately.

Memory problems and weight loss: A case report

This interesting case report illustrates a paraneoplastic syndrome presenting as dementia. A 75-year-old Malaysian lady with a 45-pack year smoking history presented with unintentional weight loss of three stone in three months with generalised aches and pains and short-term memory problems. Her inflammatory markers were raised, liver function tests were deranged, and her thyroid stimulating hormone was low. Cerebrospinal fluid examination revealed a mild increase in protein. On the Addenbrookes Cognitive Scale her score was 39/100 and she also had clinical features to suggest mild depression. A Computed Tomography of the thorax showed a 34mm mass anterior to the trachea and an enlarged right para-tracheal lymph node. Subsequent endo-bronchial ultrasound biopsy confirmed metastatic small-cell lung cancer. She had positive autoantibodies for anti-Hu and anti-Sox 1; indicating a paraneoplastic syndrome or limbic encephalitis. Paraneoplastic syndromes are rare and difficult to diagnose. In this case, the paraneoplastic manifestations mimicked a dementia illness.

Dermatomyositis and/or polymyositis as a paraneoplastic manifestation of ovarian cancer: a systematic review.

Dermatomyositis (DM) is defined as an autoimmune inflammatory disease that affects the skin, the blood vessels and the muscles. It typically presents with erythema affecting mostly the eyes and the hands as well as proximal muscle weakness. It has been also correlated with various types of cancer, including ovarian cancer. A systematic PubMed and Scopus search was conducted. A total of 110 women were included in our review. The median age of the patients was 52.5 years (8–85). The most frequent histological type of malignancy was epithelial (87 cases, 79.1%) and in only one patient (0.9%) DM was co-existing with a cancer recurrence. A clinical diagnosis of DM or PM preceded the diagnosis of ovarian cancer in 69.1% (76/110), while paraneoplastic DM after the diagnosis of ovarian cancer was reported in 31% (34/110). Serum antibodies were present in 22.5% (25/110) and the median creatine kinase during first evaluation was 886 (56.6–16,596). Postoperative improvement of the symptoms was observed in 24.6% (27/110) while also 24.6% (27/110) needed post-treatment rheumatological management. Neoadjuvant chemotherapy or radiotherapy was necessary in 58.2% (64/110) and a cancer recurrence was identified in 28.2% (31/110), with a median follow up of 24.5 months (5–210). Finally, 52 (47.3%) deaths were reported in a median follow-up period of 16 months (0–210). It is crucial that DM patients should receive a thorough evaluation for ovarian cancer, among other malignancies, encompassing an abdominal CT or MRI scan and serum Ca-125 marker measurements. Treatment of ovarian cancer is usually accompanied by remission of DM symptoms in most of the cases.

Dermatomyositis as a Paraneoplastic Manifestation of Ovarian Cancer: A Case Report and Review of Literature

Dermatomyositis (DM) is a rare autoimmune disease that occurs throughout the world. It is characterized by pathognomonic cutaneous features and symmetrical proximal muscle weakness of striated muscles of limbs, although an amyopathic form of dermatomyositis also exists. The disease is mainly idiopathic but may present as a cutaneous manifestation of cancer. Pathogenesis of DM is poorly understood, but it is believed that it is caused by altered cellular and humoral immunity. Diagnosis is based on a characteristic clinical picture confirmed by biochemistry and biopsy of skin and muscle. Treatment is mainly by steroids, immunosuppressive drugs and management of underlying malignancy. Recurrence of dermatomyositis symptoms is often the first sign of relapse. Prognosis of ovarian cancer in context of dermatomyositis is poor. We hereby report a case of DM who on investigations is diagnosed to have underlying ovarian cancer. She is managed by systemic steroids, chemotherapy and cytoreductive surgery leading to the resolution of disease which again relapsed after 1 year, again preceded by onset of rash and managed by second-line chemotherapy and monoclonal antibody.