Hypereosinophilic syndrome (HES) has three defining features: marked hypereosinophilia for at least 6 months, no confirmed etiology for the eosinophilia, and eosinophilia-related symptoms or organ dysfunction. However, a shorter period of hypereosinophilia with symptoms requiring eosinophil-lowering therapy is also acceptable. We report a case of HES presenting as eosinophilic colitis. Although hypereosinophilia was present for 3 months, this patient needed to be treated with eosionphil-lowering therapy for severe hematochezia. After systemic corticosteroid therapy, symptoms caused by organ involvement were dramatically improved.
Hypereosinophilic syndrome; Colon; Steroids
It has been reported that patients with bladder cancer have widely varying paraneoplastic consequences, including metabolic, dermatologic, myopathic and neurologic disturbances. We report a case of a 52-year-old man with advanced transitional cell carcinoma and liver metastases, who developed a severe coagulopathy following robotic radical cystoprostatectomy due to circulating heparin-like substances prior to onset of liver failure. Heparin-like anticoagulant production is a rare paraneoplastic effect documented in concert with transitional cell carcinoma, breast carcinoma and hematological malignancies.
A peptide of approximately 300-400 daltons exhibiting in vitro chemotactic activity for human polymorphonuclear (PMN) leukocytes, with a preference for the eosinophil series, was isolated from extracts of anaplastic lung carcinomas of the large squamous cell type obtained from three patients with marked peripheral blood hypereosinophilia and eosinophilic infiltration of the tumors and surrounding normal pulmonary tissues. This chemotactic factor was termed ECF-LSC (eosinophil chemotactic factor of lung squamous cell carcinoma). ECF-LSC appeared in the urine of two of the patients in increasing quantities late in the course of their disease and was also elaborated by long-term cultures of dispersed tumor cells from the same two patients. Three anaplastic large cell bronchogenic carcinomas which were not associated with tumor tissue or peripheral blood eosinophilia, a bronchogenic adenocarcinoma from a patient with only peripheral eosinophilia, and a renal cell carcinoma metastatic to the lungs and associated with transient pleural tissue and fluid eosinophilia were all devoid of ECF-LSC. ECF-LSC from tumor tissue extracts, urine, and tumor cell culture medium was comparable to the mast cell-associated tetrapeptides of the eosinophil chemotactic factor of anaphylaxis (ECF-A) in size, but eluted from Dowex-1 at pH 5.0-3.5 in contrast to the more acidic ECF-A tetrapeptides which eluted at pH 3.2-2.2 ECF-LSC, like the tetrapeptides of ECF-A, had a secondary chemotactic activity for neutrophil PMN leukocytes, but not mononuclear leukocytes, and deactivated both eosinophil and neutrophil PMN leukocytes so that they would not respond to a subsequent in vitro chemotactic stimulus. Eosinophils from the two patients with urinary excretion of ECF-LSC and the highest concentrations in tumor extracts were hyporesponsive in vitro to homologous and heterologous chemotactic stimuli, suggesting that ECF-LSC had deactivated the eosinophils in vivo.
We report here a case with hypereosinophilia and peripheral artery occlusion. A 32-yr-old Korean woman presented to us with lower extremity swelling and pain. Angiography revealed that multiple lower extremity arteries were occlusive. The biopsy specimen showed perivascular and periadnexal dense eosinophilic infiltration in dermis and subcutaneous adipose tissue. Laboratory investigations revealed a persistent hypereosinophilia. She was prescribed prednisolone 60 mg daily. Her skin lesion and pain were improved and the eosinophil count was dramatically decreased. After discharge, eosinophil count gradually increased again. Cyanosis and pain of her fingers recurred. She had been treated with cyclophosphamide pulse therapy. Her eosinophilia was decreased, but the cyanosis and tingling sense were progressive. The extremity arterial stenoses were slightly progressed. Skin biopsy showed perivascular eosinophilic infiltration in the dermis and CD40 ligand (CD40L) positive eosinophilic infiltration. The serum TNF-α was markedly increased. These results suggest that CD40L (a member of TNF-α superfamily) could play a role in the inflammatory processes when eosinophil infiltration and activation are observed. We prescribed prednisolone, cyclophosphamide, clopidogrel, cilostazol, beraprost and nifedipine, and she was discharged.
Hypereosinophilic Syndrome; Vasculitis; Tumor Necrosis Factor-alpha; CD40 Ligand
Churg-Strauss syndrome (CSS) is a rare systemic vasculitis of the small- and medium-size vessels. It is mostly seen in elderly patients presenting as de novo asthma, eosinophilia, and vasculitic organ involvement. In childhood, CSS is extremely rare. The course of pediatric CSS is usually severe and often lethal. We present a case of a 13-year-old girl with a short history of asthma, marked eosinophilia, and multiorgan involvement. The extremely high level of blood eosinophilic granulocytes (51.6 × 109/L) prompted a workup for eosinophilic leukemia before the diagnosis CSS could be made. Subsequently, the disease was successfully treated. This case report shows a classical case of childhood CSS, remarkable because of the presence of extreme hypereosinophilia. It underlines the importance of CSS as a life-threatening cause of hypereosinophilia in children.
Childhood; Churg-Strauss syndrome; CSS; Hypereosinophilia
A case is presented of the Churg-Strauss syndrome with hypereosinophilia and severe cardiac involvement, namely biventricular endomyocardial fibrosis and gross encroachment of the right ventricular cavity. The clinical picture was similar to Loeffler's syndrome and the idiopathic hypereosinophilic syndrome. Combined aggressive surgical and medical management led to full recovery and survival at 10 years. The good long term outcome is attributed to strict control of peripheral eosinophil count by oral corticosteroids. This case illustrates the damaging effects of hypereosinophilia on the heart.
Churg-Strauss syndrome; cardiac involvement; hypereosinophilia
Paraneoplastic eosinophilia is reported in dogs, cats, and humans. Hypereosinophilia (an eosinophil count greater than 1.5 x 10(9) L) is often associated with metastasis and a poor prognosis. This report describes a case of paraneoplastic hypereosinophilia in a pony. Neoplasia should be included in the differential diagnoses in a horse with eosinophilia.
Paraneoplastic cerebellar degeneration is a rare non-metastatic manifestation of malignancy. In this report, to the best of our knowledge we describe for the first time a diagnosis of paraneoplastic cerebellar degeneration several months prior to the diagnosis of clear carcinoma of the uterus.
A 75-year-old Caucasian woman manifested a rapidly progressive cerebellar syndrome with nystagmus, past-pointing, dysdiadochokinesis, dysarthria, truncal ataxia and titubation. The paraneoplastic cerebellar degeneration was associated with anti-Yo and anti-glutamic acid decarboxylase antibodies. 14-3-3 protein was detected in the cerebrospinal fluid. She was treated with intravenous immunoglobulin prior to laparotomy, hysterectomy and bilateral salpingoophorectomy. Our patient has survived for three years following diagnosis and treatment.
To the best of our knowledge this is the first report of an association of clear cell carcinoma of the uterus and paraneoplastic cerebellar degeneration with both anti-Yo and anti-glutamic acid decarboxylase antibodies. The findings imply that both antibodies contributed to the fulminating paraneoplastic cerebellar degeneration observed in our patient, and this was of such severity it resulted in the release of 14-3-3 protein in the cerebrospinal fluid, a marker of neuronal death.
14-3-3 proteins; anti-Yo/anti-GAD antibodies; clear cell carcinoma of uterus; paraneoplastic cerebellar degeneration
Chronic hepatitis associated with hypereosinophilia has been very rarely reported worldwide. A 7-month-old male infant presented with a high fever, cough, non-projectile vomiting and hepatomegaly. The eosinophil count of the peripheral blood increased up to 21,500/mm3 (49% of WBC). The infant had a history of frequent contact with a neighbor keeping a pigsty. The pathologic examinations of the liver showed severe porto-periportal necroinflammation with marked eosinophilic infiltration, giant cell transformation and ballooning degeneration of hepatocytes, and degranulation of the eosinophils. Bone marrow showed increased eosinophils and decreased myeloid series. Pericardial effusion and bilateral pulmonary consolidation were noted. Corticosteroid aggravated the clinical symptoms of the infant. Anthelmintic treatment significantly normalized the eosinophil count and liver function tests, but cardiopulmonary manifestations continued.
The first case is about a man of 60 years old suffering of hypereosinophilic syndrome (HES) developed since 1998. He presented chronic cough, insomnia, and negative parasitical test. We observed hypereosinophilia and fibroblastic hyperplasia at the bone marrow biopsy. Initially, hydroxyurea and α-interferon treatment failed. We proposed to him imatinib mesylate in May 2003. The FIP1L1-PDGFRA gene was detected. The second case is about a man of 34 years old seen in March 2002. First investigation concluded to CML. Progressively, eosinophil cells increased, and complications occurred as oedema syndrome, dyspnoea, and parietal chronic endocarditic fibrosis associated with pericarditis. In addition, a bowel obstruction happened and was cured by surgery. Bcr-abl fusion was negative, and FIP1L1-PDGFRA gene was detected after and imatinib mesylate was given. Actually, endocarditic fibrosis decreased. The two patients are in haematological and cytogenetic remission. We concluded that clonal HES is present in Africa, and imatinib mesylate is effective.
Dysphagia and weight loss are alarming symptoms that warrant urgent assessment.
We present a case report of dysphagia secondary to oesophageal dysmotility attributed to a paraneoplastic manifestation of an occult renal cell carcinoma.
We believe this patient's dysphagia was a paraneoplastic manifestation of the renal cell tumour, an association that has never been previously reported. This case demonstrates the need to look for alternative causes for dysphagia if initial investigation and treatment are unhelpful. Importantly, this must include the consideration of a paraneoplastic process secondary to an occult neoplasm.
Cholestasis is a common feature of several malignant diseases, including pancreatic, hepatic, gallbladder, and ampullary carcinomas. It is usually secondary to main bile duct obstruction or widespread hepatic metastasis, but it can also be a paraneoplastic syndrome of other underlying malignancies. Stauffer's syndrome is a rare paraneoplastic manifestation of renal cell carcinoma (RCC) that is characterized by elevated alkaline phosphatase, erythrocyte sedimentation rate, α-2-globulin, and γ-glutamyl transferase, thrombocytosis, prolongation of prothrombin time, and hepatosplenomegaly, in the absence of hepatic metastasis and jaundice. A rare variant of this syndrome with jaundice has recently been described in 3 cases in the literature. We report a patient who presented with abdominal pain and cholestatic jaundice in whom RCC was incidentally found during initial workup. Jaundice and liver dysfunction resolved completely after surgical resection of the tumor. This case illustrates the protean manifestations of RCC, and the importance of considering Stauffer's syndrome and its variant in the differential diagnosis of anicteric and icteric cholestasis, which may allow early recognition and treatment of an underlying malignancy.
jaundice; cholestasis; renal cell carcinoma; Stauffer's syndrome
The adrenal gland is one of the common sites of metastasis from primary lung cancer. Adrenal metastases are usually unilateral however bilateral adrenal metastases are seen in 10% of all lung cancer patients; of these 2–3% occurs at the initial presentation of non-small cell lung cancer. Secondary tumors can disrupt the structure and function of the adrenal. This can lead to adrenal hemorrhage, which constitutes a life threatening hazard for the patient.
A 59-year-old male presented with persisting abdominal pain. His initial work-up revealed significant anemia, an invasive process in the right upper lobe of the lung and large masses of heterogeneous texture, with hemorrhagic and necrotic elements in both adrenal glands. A biopsy confirmed it to be a large-cell carcinoma of the lungs. The patient developed severe leukocytosis akin to the paraneoplastic syndrome and died suddenly five days after the administration of chemotherapy.
Intratumoral hemorrhage is a rare but life threatening complication of adrenal metastases and should be treated as soon as it has been diagnosed. If adrenalectomy is not feasible, combination chemotherapy should be applied as in metastatic disease. For choosing the appropriate chemotherapeutic regimen it is important to accurately achieve the diagnosis.
Lung cancer is the leading cause of death among the cancers seen in the United States. Hypercalcemia and leukocytosis are two common paraneoplastic syndromes associated with lung cancer. Unfortunately patients presenting with Hypercalcemia- leukocytosis syndrome has a worse prognosis than patients presenting with lung cancer alone.
We present a 67 yr old Caucasian male with a history of active smoking presenting as pneumonia being diagnosed as cavitating squamous cell carcinoma of the lung with hypercalcemia-leukocytosis syndrome
There should be a high degree of suspicion to diagnose lung cancer in patients presenting with symptoms of paraneoplastic syndrome.
RENAL CELL CARCINOMA IS CHARACTERIZED by varied manifestations, which include unusual metastatic sites and paraneoplastic and vascular syndromes. We describe the case of a 57-year-old man who presented with high fever, weight loss, palpitations and a tender goitre. We suggest that, in this patient, subacute thyroiditis manifested as a paraneoplastic syndrome of renal cell carcinoma.
Paraneoplastic dermatomyositis (DM) associated with testicular cancer is extremely rare. We report the case of a patient with skin tightening, polymyalgia, hypereosinophilia, and nodular regenerative hyperplasia revealing seminoma and associated paraneoplastic DM.
Eosinophilic endocarditis is a potentially lethal complication of chronic peripheral blood hypereosinophilia. We hypothesized that eosinophil peroxidase (EPO), an abundant eosinophil (EO) cationic granule protein, promotes eosinophilic endocarditis by binding to negatively charged endocardium, and there generating cytotoxic oxidants. Using an immunocytochemical technique, we demonstrated endocardial deposition of EPO in the heart of a patient with hypereosinophilic heart disease. Because EPO preferentially oxidizes Br- to hypobromous acid (HOBr) rather than Cl- to hypochlorous acid (HOCl) at physiologic halide concentrations, we characterized the Br(-)- dependent toxicity of both activated EOs and purified human EPO towards several types of endothelial cells and isolated working rat hearts. In RPMI supplemented with 100 microM Br-, phorbol myristate acetate- activated EOs, but not polymorphonuclear leukocytes, caused 1.8-3.6 times as much 51Cr release from four types of endothelial cell monolayers as in RPMI alone. H2O2 and purified human EPO, especially when bound to cell surfaces, mediated extraordinarily potent, completely Br(-)-dependent cytolysis of endothelial cells that was reversed by peroxidase inhibitors, HOBr scavengers, and competitive substrates. We further modeled eosinophilic endocarditis by instilling EPO into the left ventricles of isolated rat hearts, flushing unbound EPO, then perfusing them with a buffer containing 100 microM Br- and 1 microM H2O2. Acute congestive heart failure (evidenced by a precipitous decrement in rate pressure product, stroke volume work, aortic output, and MVO2 to 0-33% of control values) ensued over 20 min, which deletion of EPO, Br-, or H2O2 completely abrogated. These findings raise the possibility that EPO bound to endocardial cells might utilize H2O2 generated either by overlying phagocytes or endogenous cardiac metabolism along with the virtually inexhaustible supply of Br- from flowing blood to fuel HOBr-mediated cell damage. By this mechanism, EPO may play an important role in the pathogenesis of eosinophilic endocarditis.
Five patients were seen in whom a raised serum calcium concentration was associated with ovarian carcinoma (clear cell in two cases, cystadenocarcinoma in three). None showed evidence of metastases in bone. The hypercalcaemia occurred as a paraneoplastic phenomenon, but biochemical studies suggested the production of a parathyroid-hormone-like substance. One patient remained free of symptoms of her hypercalcaemia throughout. Paraneoplastic hypercalcaemia due to ovarian carcinoma may be more common than generally recognised and present as a life threatening condition requiring urgent treatment.
A 95-year-old woman had been treated over the past 8 years for progressive dysphagia. When her condition worsened, blood tests revealed the presence of leucocytosis and eosinophilia in the absence of anaemia or thrombocytopenia. Within 11 days of diagnosis, the patient died of respiratory failure. Necropsy showed normal thyroid tissue and an absence of infectious disease. However, an upper mediastinal tumour was found and was histopathologically diagnosed as a neoplastic transformation of the ectopic thyroid. Only 1% of endothoracic goitres present as ectopic or autonomous goitre with no parenchymal or vascular connection to the thyroid gland. This case represents a very rare situation in which a leukemoid reaction and peripheral hypereosinophilia were observed as a manifestation of an anaplastic thyroid carcinoma in an ectopic mass.
The mechanisms of sustained overproduction of eosinophils in the idiopathic hypereosinophilic syndrome and in some human immunodeficiency virus (HIV)-1-infected individuals are largely unknown. We hypothesized that T cells may release soluble products that regulate eosinophilia in these patients, as has been previously shown in bronchial asthma. We identified one patient with idiopathic hypereosinophilic syndrome and one HIV-1-infected individual with associated hypereosinophilia who demonstrated high numbers of CD4-CD8- T cells in peripheral blood. CD4-CD8- T cells from both patients, although highly activated, did not express functional Fas receptors. In one case, the lack of functional Fas receptors was associated with failure of Fas mRNA and protein expression, and in another, expression of a soluble form of the Fas molecule that may have antagonized normal signaling of Fas ligand. In contrast to the recently described lymphoproliferative/autoimmune syndrome, which is characterized by accumulation of CD4-CD8- T cells and mutations within the Fas gene, this study suggests somatic variations in Fas expression and function quite late in life. Both genetic and somatic abnormalities in regulation of the Fas gene are therefore associated with failures to undergo T cell apoptosis. Furthermore, the expanded population of CD4- CD8- T cells from both patients elaborated cytokines with antiapoptotic properties for eosinophils, indicating a major role of these T cells in the development of eosinophilia. Thus, this study demonstrates a sequential dysregulation of apoptosis in different cell types.
Paraneoplastic syndromes are often associated with renal parenchymal tumours. This report describes a case of renal-cell carcinoma with kappa-chain nephropathy. The patient, a 60-year-old man, had renal tubular dysfunction, shown by low serum concentrations of urate and phosphate. Kappa-chains were found in both serum and urine, but no lambda-chains were found. Investigations showed a clear-cell carcinoma, and the patient underwent a radical nephrectomy. Two years after operation serum phosphate and urate concentrations had returned to normal, and kappa-chains were undetectable in serum or urine. The absence of lambda-chains indicates that the light-chain proteinuria was due to overproduction of the M component, and the disappearance of kappa-chains after the operation suggests a causal relation between the renal tumour and the overproduction of the M component.
The Paraneoplastic syndromes include the disorders that accompany benign or malignant tumors but are not directly related to mass effects or invasion by the primary tumor or its metastases. Neoplastic cells can produce a variety of peptides that exert biologic actions at local and distant sites and can elicit responses that cause a variety of hormonal, hematologic, dermatologic and neurologic symptoms. Almost every type of malignancy has the potential to produce hormones or cytokines or to induce immunologic responses. Lung cancers, both non-small cell and small cell, are capable of producing a variety of paraneoplastic syndromes. The majority of such syndromes are caused by small cell carcinomas, including many endocrinopathies. Syndrome of inappropriate antidiuretic hormone (SIADH) has been commonly associated with small cell carcinoma and is often seen in these patients. However, SIADH associated with squamous cell carcinoma has rarely been reported on, and the mechanism for this rare association is still unknown. We present here a case of a 77-yr-old man who developed SIADH caused by squamous cell carcinoma of the nasopharynx.
SIADH; Hyponatremia; Squamous cell carcinoma; Neuropeptide Y; Neck dissection
Paraneoplastic syndromes (PNS) are a heterogeneous group of symptoms which are indirectly caused by primary or metastatic tumor. Paraneoplastic polyneuropathy (PNP) is mostly related to small cell lung cancer (5%), prostate, gastric, and breast cancer. Only sporadic cases have been reported to be associated with endometrial cancer. We present a case of a premenopausal woman with severe vasculitic, asymmetric sensorimotor polyneuropathy that developed in conjunction with an endometrial carcinoma responding to surgical therapy of primary tumor combined to steroid therapy. Neurological symptoms such as asymmetrical sensorimotor deficits and painful paresthesias are suspicious when they occur in otherwise healthy women with no medical history. The phenomenon of a paraneoplastic syndrome can point to an underlying malignancy and can be used as marker of progression or regression of the tumor. Due to the rarity of PNP, there is no standard treatment. Recommended therapy is stage-adjusted treatment of the primary tumor.
Many cancers are known to be associated with paraneoplastic syndromes. These syndromes are usually treated by chemotherapy with or without immunosupression but they often respond poorly. There are no published reviews on response to endocrine treatment.
We report a case of a patient presenting with papillitis, myositis and sensory peripheral neuropathy 18 months before a diagnosis of metastatic oestrogen receptor positive breast cancer was confirmed. The patient was treated with anastrozole which led not only to a decrease of her tumour burden but also to an improvement in her biochemical markers and amelioration of her clinical symptoms.
This case is an example of breast cancer presenting with paraneoplastic manifestations. It took several months to establish the cause of symptoms in this patient thus illustrating the need for physicians to maintain a high index of suspicion for paraneoplastic syndromes in women presenting with unusual neurological symptoms with no obvious cause.
It is a unique case as it illustrates how treatment with an aromatase inhibitor leading to cancer regression can result in an improvement in the paraneoplastic symptoms.
Sarcomatoid carcinoma is an extremely rare biphasic tumor characterized by a combination of malignant epithelial and mesenchymal cells. Limited data on sarcomatoid carcinoma showed that most cases occurred with advanced local disease and metastasis, and paraneoplastic syndromes were rare. We present the case of a 63-year-old man with lung
sarcomatoid carcinoma associated with jejunum metastasis and leukocytosis, and its clinical, macroscopic, and histopathological features. This case emphasizes the importance of recognizing paraneoplastic syndromes and metastasis of sarcomatoid carcinoma at diagnosis.
lung cancer; sarcomatoid carcinoma; leukocytosis