Paraneoplastic Process Research Articles

Gyrate Erythema and Melanoma—A New Clinical Association

The authors present the case of a 65-year-old gentleman with a 2.6-mm Breslow thickness melanoma on the lower limb. During his treatment, he underwent several operations including a partial foot amputation. At clinical review, he was noted to have developed an unusual rash. This rash, an annular and gyrate erythema, has never been described before in relation to melanoma, and is sometimes seen in the presence of paraneoplastic processes. Highlighting this new association may enable clinicians to understand and appreciate melanoma better in the future.

Paraneoplastic Scleroderma-Like Tissue Reactions in the Setting of an Underlying Plasma Cell Dyscrasia

Systemic plasma cell dyscrasias have diverse manifestations in the skin and include an inflammatory paraneoplastic process. We encountered cases of scleroderma and eosinophilic fasciitis in the setting of an underlying plasma cell dyscrasia. Ten cases of scleroderma-like tissue reactions in the setting of an underlying plasma cell dyscrasia were encountered. The biopsies were stained for Transforming growth factor (Transforming growth factor) beta, IgG4, kappa, and lambda. Patients presented with a sclerodermoid reaction represented by eosinophilic fasciitis (5 cases), morphea (3 cases), and systemic scleroderma (2 cases). The mean age of presentation was 70 years with a striking female predominance (4:1). Acral accentuation was noted in 8 cases. In 6 of the cases, the cutaneous sclerosis antedated (4 cases) by weeks to 2 years or occurred concurrently (2 cases) with the initial diagnosis of the plasma cell. The biopsies showed changes typical of eosinophilic fasciitis and/or scleroderma. In 5 cases, light chain-restricted plasma cells were present on the biopsy. There was staining of the plasma cells for Transforming growth factor beta in 3 out of 5 cases tested. In any older patient presenting with a sudden onset of eosinophilic fasciitis or scleroderma especially with acral accentuation, investigations should be conducted in regards to an underlying plasma cell dyscrasia.

Multiple Reticulohistiocytomas in an 88-year-old Man: a Case Report

Abstract Solitary and multiple reticulohistiocytomas, often referred to as diffuse cutaneous reticulohistiocytosis, that are generally restricted to skin, must be differentiated from multicentric reticulohistiocytosis. Multicentric reticulohistiocytosis is a rare histiocytic proliferative disease affecting joints, skin and mucous membranes, while arthropathy usually precedes skin and mucosal involvement. Other organs may also be involved, and 20% of patients have an associated internal malignancy. Multicentric reticulohistiocytosis has been reported to be associated with autoimmune diseases and malignancies. We present an 88-year-old man, with a sudden eruption of asymptomatic, firm, skin to brown colored papules and nodules, 6 to 17 mm in diameter, localized on forehead, arms, legs, and buttocks. There were no symptoms of joint or other organ involvement. Clinical and dermoscopic characteristics pointed to reticulohystiocytomas. Multiple excision biopsies of different tumors were performed and histopathology reports confirmed the diagnosis. In the case presented, reticulohistiocytosis was limited to the skin, exhibiting multiple reticlohistiocytomas with typical clinical, dermoscopic and rather peculiar histopathology presentation. Apart from this, some histologic features were seen in early lesions of multicentric reticulohistiocytosis, such as multinuclear cells dissociating collagen fibers with pale eosinophilic and foamy cytoplasm. Besides surgical excisions, no other treatment options were done. Laboratory and other tests showed no presence of extracutaneous illness, and no autoimmune or paraneoplastic processes. At one year follow up, the remaining tumors were of the same size, but there were no recurrences at excision sites, no signs of disease progression or systemic involvement. Since diffuse cutaneous reticulohistiocytosis without arthropathy as well as isolated reticulohistiocytomas have been described, in some cases of multiple reticulohistiocytomas even without systemic symptoms and signs, multicentric reticulohistiocytosis should be considered with an appropriate follow up. In such cases, skin lesions have the same histological features as lesions in multicentric reticulohistiocytosis, but they are not associated with joint problems or neoplasms.

Severe autoimmune hemolytic anemia with renal neoplasm

Autoimmune hemolytic anemia is a type of hemolytic anemia characterized by autoantibodies directed against red blood cells shortening their survival. When autoimmune hemolytic anemia is secondary to a paraneoplastic process, severe anemia can occur leading to significant morbidity and even mortality. Here we discuss the literature and present the case of a child with autoimmune hemolytic anemia from a paraneoplastic syndrome secondary to a renal tumor.

The dance of death

I have been consulted, as a general internist, to assist in the management of an elderly and frail patient. I am asked to assess if there could be an underlying malignancy giving rise to a paraneoplastic process. It seemed unlikely to me that this was the case but I was wrong. Physical examination

An Unusual Case of Ogilvie Syndrome in a Pediatric Oncology Patient Receiving Palliative Care after Failed Treatment with Neostigmine

We present a case of severe refractory constipation in an adolescent oncology patient with widely metastatic clear cell osteosarcoma who was ultimately found to have Ogilvie syndrome, also known as acute colonic pseudo-obstruction (ACPO). Ogilvie syndrome is characterized by dilatation of the large intestine in the absence of mechanical obstruction, usually occurring in adult patients with serious underlying medical conditions and rarely seen in children. It is likely that chronic narcotic use, abdominal metastasis, and a paraneoplastic process contributed to development of ACPO in this patient. This case highlights an infrequent, but important, gastrointestinal complication that can occur in pediatric patients with serious comorbid disease. Ogilvie syndrome should be included on the differential diagnosis list in pediatric patients with refractory constipation. Our case illustrates the progression of therapies, including surgical intervention that can be undertaken to treat this disorder in children and adults while providing important considerations for clinicians treating patients of any age with this unusual clinical complication.

Anti Hu Syndrome With Atypical Electrodiagnostic Findings

Anti-Hu syndrome is a paraneoplastic process associated with lung malignancy. Patients usually present with a sensory neuropathy, cerebellar syndrome or limbic encephalitis. Although motor involvement is described it is relatively rare and forms part of a more complex presentation with multiple systems affected. doi:10.4021/jnr111w

Diffuse skin hyperpigmentation in CD30+ lymphoproliferation

CD30+ T-cell lymphoproliferative disorders (LD) comprise two main groups of diseases: CD30+ LD of the skin and systemic anaplastic large cell lymphoma (ALCL). The main feature of these disorders is the expression of CD30. We present a patient with an unusual clinical presentation of CD30+ lymphoproliferative disease in a 54-year old Caucasian male who presented with generalized lymphadenopathy and pronounced skin hyperpigmentation. In the lymph nodes and skin, CD30+ lymphoproliferation (ALCL) was diagnosed. The Prussian blue staining identified that the pigment responsible for the skin color was hemosiderin. Chemotherapy was started but the patient’s condition progressively worsened and he died a week after the first cycle. The complete color transformation of the entire skin due to hemosiderin accumulation is, to the best of our knowledge, the first reported observation in a CD30+ lymphoproliferation/ALCL patient. We speculate that hemosiderin-loaded macrophages resulted from the paraneoplastic process by some still unknown mechanism.

Ogilvie Syndrome in a Child With Incurable Malignancy (779)

1.Recognize the signs and symptoms of acute colonic pseudo-obstruction (Ogilvie Syndrome) in patients with serious underlying medical conditions.2.Identify invasive and non-invasive treatment modalities for patients with Ogilive syndrome Acute colonic pseudo-obstruction. (ACPO), also known as Ogilvie Syndrome, is characterized by dilatation of the large intestine in the absence of mechanical obstruction; it usually occurs in adult patients with serious underlying medical conditions and is rarely seen in children. A 16 year-old girl, diagnosed with metastatic small cell osteosarcoma in April 2008, was referred to our quality-of-life service with incurable disease in July 2009. Her illness was complicated by ascites of unknown origin and pain secondary to extensive metastatic disease. Her pain was under reasonable control until the fall of 2010 when she began experiencing abdominal distension, gas retention, and constipation initially treated with metoclopramide and rectal tube. Progressive pain and distension resulted in an extensive evaluation, including colonoscopy, yielding the diagnosis of Ogilvie Syndrome. It is likely that chronic narcotic use, abdominal metastasis, and a paraneoplastic process contributed to development of ACPO in this patient. First line treatment for ACPO is conservative management with bowel rest and mechanical decompression. The case patient failed conservative measures and a trial of pharmacological therapy with neostigmine was undertaken based on efficacy data from the adult literature. Unfortunately, patient experienced a severe anaphylactic reaction with bronchospasm after administration of the first dose precluding future use. We urge clinicians to use caution, such as having anaphylactic medications available, if using this medication in patients with Ogilvie Syndrome and encourage further research in pediatric patients. After thoughtful reflection, the case patient elected to undergo aggressive therapy with a diverting ileostomy and had near immediate relief of her symptoms which persisted for 6 months. This case highlights an infrequent, but important, gastrointestinal complication which can occur in pediatric patients with serious co-morbid disease. It also illustrates the progression of therapies that can be undertaken to treat this disorder in children.

“Now I Understand”: Utilizing Family Meetings To Improve Communication and Comprehension in Palliative Care (780)

Case Description. A 16 year-old girl, diagnosed with metastatic small cell osteosarcoma in April 2008, was referred to our quality-of-life service with incurable disease in July 2009. Her illness was complicated by ascites of unknown origin and pain secondary to extensive metastatic disease. Her pain was under reasonable control until the fall of 2010 when she began experiencing abdominal distension, gas retention, and constipation initially treated with metoclopramide and rectal tube. Progressive pain and distension resulted in an extensive evaluation, including colonoscopy, yielding the diagnosis of Ogilvie Syndrome. It is likely that chronic narcotic use, abdominal metastasis, and a paraneoplastic process contributed to development of ACPO in this patient. First line treatment for ACPO is conservative management with bowel rest and mechanical decompression. The case patient failed conservative measures and a trial of pharmacological therapy with neostigmine was undertaken based on efficacy data from the adult literature. Unfortunately, patient experienced a severe anaphylactic reaction with bronchospasm after administration of the first dose precluding future use. We urge clinicians to use caution, such as having anaphylactic medications available, if using this medication in patients with Ogilvie Syndrome and encourage further research in pediatric patients. After thoughtful reflection, the case patient elected to undergo aggressive therapy with a diverting ileostomy and had near immediate relief of her symptoms which persisted for 6 months.

Anti Hu Syndrome With Atypical Electrodiagnostic Findings

Anti-Hu syndrome is a paraneoplastic process associated with lung malignancy. Patients usually present with a sensory neuropathy, cerebellar syndrome or limbic encephalitis. Although motor involvement is described it is relatively rare and forms part of a more complex presentation with multiple systems affected. J Neurol Res. 2012;2(3):119-122 doi: https://doi.org/10.4021/jnr111w

Teaching Neuro Images : Punctuate and curvilinear enhancement peppering the pons responsive to steroids

A 48-year-old man developed progressive vertigo, ataxia, and dysarthria. MRI demonstrated gadolinium-enhancing abnormalities in the pons and cerebellar peduncles (figure, A). Further investigations excluded neurosarcoidosis, CNS lymphoma, granulomatosis, and paraneoplastic or chronic infectious processes. In particular, 2 CSF examinations revealed mildly elevated protein levels (0.73 g/L, N < 0.40 g/L) without pleocytosis, tumoral cells, or oligoclonal bands. Figure Initial T1-weighted postgadolinium brain MRI (A) Symmetric enhancement of the pons and both cerebellar peduncles, with pattern highly suggestive of a perivascular distribution. (B) Near complete resolution with corticosteroids. (C) Recurrence of the same lesions without corticosteroids. The patient was treated with IV …

Functional colonic obstruction in an adult as a presenting feature of thymoma

Functional colonic obstruction is a colonic motility disorder with a number of causes. One cause is myenteric ganglionitis, which may result from paraneoplastic processes. We present the case of a previously healthy 53-year-old man who presented with a week's history of functional colonic obstruction. A transverse loop colostomy failed to resolve his symptoms and he subsequently underwent an extended right hemicolectomy. Histology demonstrated lymphocytic myenteric ganglionitis that was felt to be of paraneoplastic origin. The patient later developed bilateral ptosis and was diagnosed with ocular myasthenia gravis. Further investigation revealed the presence of a thymoma that was resected, resulting in an improvement to his symptoms. We present this case and a review of the literature to illustrate the importance of seeking out a paraneoplastic cause for functional colonic obstruction in adults as early resection of the tumour may help alleviate symptoms and avoid bowel surgery.

A 10-Year-Old Boy with Muscle Cramps

A 10-year-old boy was evaluated for a 4-month history of muscle cramps. Initially, the cramps occurred twice weekly, usually in his calves. More recently, he had been having cramps in both arms and hands which lasted for up to 5 minutes. On occasion, his fi ngers would get “stuck” for several minutes before he could straighten them. Although he still participates in gym class, his mother reported he had become more cautious about physical activity. There was no history of fever, chills, night sweats, weight loss, visual problems, nausea, vomiting, or diarrhea, although in the past year, he also has noted “dark spots” on his ankles and lower extremities. His past history was unremarkable, although his brother has autism with sensory integration problems. On exam, the patient was alert and appeared healthy. Weight and height were in the 50th percentile. Pulse 88, respiratory rate 16, blood pressure 107/61. There were several 2 to 3 cm hyperpigmented patches with irregular borders on his lower extremities. HEENT exam was unremarkable. Lungs were clear. S1 and S2 were normal without murmurs, rubs, or gallops. Abdomen was soft and non-tender without masses or organomegaly. He was Tanner 1. Both testes were descended. Back was straight. Extremities were normal. Muscle mass was normal without tenderness. On neurologic examination, deep tendon refl exes were 2+ bilaterally. Toes were downgoing. Muscle strength was 5/5 throughout. Cranial nerves II through XII were intact. On initial laboratory evaluation, hemoglobin was 9.7 g/dL, white blood cell count 8,600/mm3 with 45% neutrophils, 41% lymphocytes, 10% monocytes; platelet count 178,000 mm3. MCV was 74, MCH 21, RDW 22 (normal 12.5-16), reticulocyte count 4.5%. Chem14 and ionized calcium were normal save for an albumin of 2 g/dL. GGT was normal. Sedimentation rate and C-reactive protein were normal; CPK was 510 IU/L (normal 27-248 IU/L). Robert Listernick, MD, moderator: I know this may be a profound metaphysical, philosophical question, but what’s a muscle cramp? Nancy Kuntz, MD, pediatric neurologist: You couldn’t have picked a topic more sure to create excitement and argument among neuromuscular specialists than, “What are cramps?” and “What does one do about them?” Both clinicians and patients refer to cramps as persistent or continuous unwanted muscle activity beyond what’s functional. The sensation of “getting stuck” is myotonia, in which there’s delay in relaxation of the muscles; the contraction is normal, but muscle membrane abnormalities make it diffi cult for the muscle to relax. Myotonia is uncomfortable, and people complain about pain. In the evaluation of cramps, family history is important, looking for other individuals with cramping, weakness, or who have the sensation of muscles “getting stuck.” What some patients label “cramps” is instead myokymia — localized involuntary muscle quivering — which may be caused by certain drugs or occur as a result of a paraneoplastic process. Finally, sometimes a cramp is just a cramp. Dr. Listernick: Are there clues on exam to the presence of myotonia rather than simple cramps? Dr. Kuntz: One clue is the presence of percussion myotonia. You hit a relaxed muscle with a refl ex Dr. Listernick is professor of pediatrics at Feinberg School of Medicine, Northwestern University, and director of the Diagnostic and Consultation Service, Division of General Academic Pediatrics, Children’s Memorial Hospital, Chicago, IL. fi rm rounds • fi rm rounds • • fi rm rounds • fi rm rounds

Electronic Updates for JTO Readers

In this issue of Journal of Thoracic Oncology (JTO), we have included our first video clip in the article by Nadal and colleagues.1 It is an excellent example of opsoclonus myoclonus syndrome (OMS) as a paraneoplastic process. This is a wonderful example of this entity and demonstrates the power of a video clip to help educate us. We have accepted another short video clip for a future issue. I would encourage all of you to keep this possibility in mind for potential submission to JTO. I hope this video clip will be the first of many.

Bilateral Hand Weakness and Numbness

HISTORY: 51year old right-handed male who had 3 months of tingling in his right hand's fingers. He rapidly developed weakness of the boht hands in the next few months. His arms felt "heavy" and he was having difficulty performing daily activities such as dressing himself, shaving, and eating. By presentation, the symptoms were equal in both hands/arms. He also endorses a 5 kg weight loss. The patient smokes about 1 PPD since age 16 and drinks alcohol socially. He worked as a materials handler at a federal mint until a few months ago, when he stopped working due to hand weakness. PHYSICAL EXAMINATION: CN II-XII were intact. There was noticeable atrophy in both hands with occasional fasciculations. Strength in the proximal arms was normal. He had diminished 2-3/5 strength in finger extension, 3-4/5 in finger abduction, 4/5 in finger flexion, and 4/5 in thumb abduction. Lower extremities had full strength. Reflexes were 2+ and symmetric. There was decreased pinprick sensation in the lower forearms and hands and decreased vibratory sensation in both hands. DIFFERENTIAL DIAGNOSIS: 1. Inflammatory/immune polyneuropathy 2. Brachial plexopathy 3. Paraneoplastic process 4. Vasculitis 5. Cervical spine disease with ulnar neuropathy TEST AND RESULTS: Blood work: B12, ESR, RF, ANA, HCV, pareneoplastic panel, and TSH are unremarkable. CSF with slightly high protein, but otherwise normal.No systemic markers of vasculitis. MRI: Moderate to severe spinal stenosis at C6/7 with bilateral neuroforaminal narrowing (symptoms do not correlate to this level) Moderate spinal stenosis at C5/6 and C7/T1 No abnormality of either brachial plexus Degenerative changes in lower c-spine with moderate canal and neuroforaminal stenosis EMG: Decreased ulnar sensory and motor function; median and radial nerves normal Severe chronic partial denervation in 1st dorsal interosseous and flexor digitorum profundus Other C7-innervated muscles showed mild chronic partial denervation FINAL/WORKING DIAGNOSIS: Lewis-Sumner Syndrome (variant of chronic inflammatory demyelinating polyneuropathy) TREATMENT AND OUTCOMES: 1. Oral prednisone. Follow-up in 4 months showed no further progression of peripheral neuropathy 2. Steroids will be continued for 3 months, if no evidence of axonal regeneration then IV gamma globulin will considered 3. Physical therapy

Pulmonary Amyloidosis as a Paraneoplastic Process in Head and Neck Cancer

The LaryngoscopeVolume 121, Issue S4 p. S134-S134 Triological Society 2011 Combined Sections Meeting Posters Pulmonary Amyloidosis as a Paraneoplastic Process in Head and Neck Cancer Matthew K. Lee M.D, Matthew K. Lee M.D Division of Head and Neck Surgery, David Geffen School of Medicine at UCLASearch for more papers by this authorAbie H. Mendelsohn M.D, Abie H. Mendelsohn M.D Division of Head and Neck Surgery, David Geffen School of Medicine at UCLASearch for more papers by this authorPaul A. Kedeshian M.D, Paul A. Kedeshian M.D Division of Head and Neck Surgery, David Geffen School of Medicine at UCLASearch for more papers by this author Matthew K. Lee M.D, Matthew K. Lee M.D Division of Head and Neck Surgery, David Geffen School of Medicine at UCLASearch for more papers by this authorAbie H. Mendelsohn M.D, Abie H. Mendelsohn M.D Division of Head and Neck Surgery, David Geffen School of Medicine at UCLASearch for more papers by this authorPaul A. Kedeshian M.D, Paul A. Kedeshian M.D Division of Head and Neck Surgery, David Geffen School of Medicine at UCLASearch for more papers by this author First published: 28 June 2011 https://doi.org/10.1002/lary.22011AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume121, IssueS4Supplement: Triological Society 2011 Combined Sections Meeting Posters2011Pages S134-S134 RelatedInformation

Voltage-Gated Potassium Channel-Complex Antibody-Associated Limbic Encephalitis

Limbic encephalitis is characterized by the subacute progression of short-term memory loss, disorientation, confusion, and agitation. Hallucinations, behavioral and personality changes, temporolimbic seizures, sleep disturbances, and dysautonomia may also occur. The pyramidal layer of the hippocampus and the amygdaloid nuclei are particularly susceptible and demonstrate neuronal loss, reactive gliosis, and perivascular lymphocytic cuffing. Magnetic resonance imaging (MRI) typically reveals increased signal in limbic structures on T2, fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging (DWI). Historically, limbic encephalitis has been conceptualized as a paraneoplastic process characterized by autoantibodies associated with underlying neoplasms: small cell lung, lymphoma, thymoma, testicular, breast, teratoma, prostate, rectal, retinoblastoma, oligodendroglioma, melanoma, and leiomyosarcoma. Although a definitive pathophysiologic mechanism for autoimmune limbic encephalitis remains unknown, multiple autoantibodies are implicated, including voltage-gated potassium channel complex antibodies (VGKC-complex Ab.) Idiopathic autoimmune limbic encephalitis also occurs. We present the longitudinal course of a man who developed cognitive and behavioral disturbances ultimately attributed to VGKC complex autoimmunity.

An Unusual Presentation of Liver Failure in a Patient with Primary Gastrointestinal Hodgkin's Lymphoma

Introduction. Hodgkin's lymphoma (HL) presenting either with primary bowel involvement or with cholestasis is unusual. The combination of primary gastrointestinal HL presenting with cholestasis and ductopenia has not been previously described. Case Report. We present a case of primary gastrointestinal HL with evidence of liver involvement, but also with prominent ductopenia on liver biopsy and associated intrahepatic cholestasis. A 50-year-old man with a history of Crohn's disease presented with a bowel obstruction, for which he underwent a small bowel resection. Histology revealed HL. His course was complicated by cholestatic liver failure. A subsequent liver biopsy revealed both focal involvement by lymphoma and ductopenia, resembling vanishing bile duct syndrome (VBDS). He was treated with chemotherapy with improvement in his cholestasis, but he eventually succumbed due to further complications of his disease and treatment toxicities. Conclusion. This case of primary gastrointestinal HL associated with ductopenia does not meet classic criteria for VBDS, but the clinical presentation and pathology are suggestive of a VBDS-like paraneoplastic process. Therapies for HL in the setting of cholestatic liver failure require special consideration, but some reports of durable remissions and recovery of liver function have been reported.

Headache in Patients with Cancer

Contemporary cancer research has led to unparalleled advances in therapeutics and improved survival. Even as treatment options continue to improve, quality of life should remain a priority. Headache drastically impacts the quality of life of patients with cancer and has a wide etiological scope, making diagnosis a challenge. Intracranial mass lesions are only one cause; others include extracranial tumors, paraneoplastic processes, and the consequences of diagnostic and therapeutic interventions used in cancer care. Fortunately, cancer-related headache is treatable, but a sound understanding of the variable etiologies is crucial to appropriate diagnostic evaluation and treatment. In this review, we highlight the important causes of headache in the patient with cancer, and consider the epidemiology, pathophysiology, clinical course, and treatment options for each.