Mild Normocytic Anemia Research Articles

S1745 Not All Colonic Masses Are Adenocarcinoma

INTRODUCTION: Acute lymphoblastic leukemia (ALL) is a hematologic malignancy primarily affecting bone marrow, but with potential for blast cell to infiltrate extramedullary structures, most commonly the central nervous system. The gastrointestinal tract is not considered a primary site of disease involvement unless disease relapses. CASE DESCRIPTION/METHODS: A 20 year old man with celiac disease and Philadelphia negative, CD20+ B-cell ALL presented with abdominal pain. ALL was diagnosed 10 months prior and followed by treatment with AYA protocol of CALGB 10403 chemotherapy regimen, which consisted of vincristine, daunorubicin, pegaspargase, and prednisone. Rituximab was added due to CD20 + status. Regimen adjustment was required due to adverse effects of hepatitis and pancreatitis related to pegaspargase. After receiving 2 cycles of blinatumomab, a bone marrow biopsy supported clinical remission. Four weeks thereafter, the patient presented with severe abdominal pain, worse in the right lower quadrant. Exam revealed diffuse abdominal tenderness. Labs noted a mild normocytic anemia of 11.9 g/dL and thrombocytopenia of 119 K/MM3. Abdominal computed tomography measured 1.8 cm wall thickening in the appendix and cecum. Colonoscopy demonstrated multiple large, smooth, and firm polypoid masses in the cecum, with smaller satellite lesions in the ascending colon, an additional fungating mass in the distal ascending colon. Colonic mass biopsies demonstrated extensive leukemic infiltrate, consistent with B-ALL, which stained positive for PAX5, CD10, CD34, TdT, and negative for CD20. Chemotherapy and immunotherapy was reinitiated, with future plans for stem cell transplant. DISCUSSION: Although ALL with GI involvement is rarely reported, leukemic GI infiltration is identified in up to 25% of autopsies. As immune therapy has been theorized to leave extramedullary compartments vulnerable to incomplete disease eradiation, there is a potential for disease to exist undetected. Support for early endoscopy in patients undergoing immunotherapy and presenting with GI complaints may help to exclude GI involvement prior to declaring remission. A future prospective trial to identify risk factors for patients with ALL at high risk for GI infiltration would be valuable to determine those more likely to benefit from early endoscopic evaluation, and thus avoid unnecessary procedures in a population already at elevated procedural risk due to immunocompromised state and common presence of cytopenias.Figure 1.: Picture 1: CT abdomen/pelvis depicting cecal thickening of 18.47 mm.Figure 2.: Picture 2: A & B Colonoscopic findings of cecal masses, C. Colonoscopic findings of distal ascending colon mass.Figure 3.: Picture 3: A. Histology of leukemic infiltration in the colon, B. PAX5 positive immunohistochemistry staining, C. CD34 positive immunohistochemistry staining, D. TdT positive immunohistochemistry staining.

S2290 Venous and Arterial Thromboembolism: Unusual Harbinger of Ulcerative Colitis in a 64-Year-Old

INTRODUCTION: Arterial and venous thromboembolic events are known extraintestinal manifestations of inflammatory bowel disease (IBD). Since elderly patients with IBD require tailored treatment strategies, establishing the initial diagnosis and assessing the etiology of future symptoms are critical. We present a 64-year-old male who underwent left iliofemoral vein and artery thrombectomy for phlegmasia with subsequent diagnosis of severe active ulcerative colitis. CASE DESCRIPTION/METHODS: A 64-year-old otherwise healthy white male presented with a 3-month history of abdominal pain, hematochezia, 20 lb unintentional weight loss, and left lower extremity pain. He quit smoking one year prior to presentation and denied family history of IBD or colon cancer. Vital signs were stable and physical exam revealed left leg swelling and tenderness, cyanosis of the left great toe, and positive fecal occult blood test. Labs showed mild normocytic anemia and elevated fecal calprotectin. The abdominal CT showed thrombosis of the left femoral vein, right sided subsegmental pulmonary embolus, distal abdominal aorta mural thrombus, and left iliac artery occlusion (Figure 1). Anticoagulation was not initiated given concerns for lower gastrointestinal bleed. An Inferior Vena Cava filter was placed the following day with stenting of the left common and external iliac arteries, and thrombectomy of the left common femoral, superficial femoral, and external iliac veins. A colonoscopy showed severe inflammation from the rectum to the descending colon (Figure 2). Colonic biopsies showed active chronic colitis with cryptitis and crypt abscesses consistent with ulcerative colitis (UC). Patient was started on steroids, discharged on hospital day 5, and readmitted 5 days later for right leg pain. The Doppler ultrasound showed an occlusive acute Deep Vein Thrombosis (DVT) of the right posterior-tibial vein, nonocclusive DVT of the right common femoral, superficial femoral, and popliteal veins, and occlusion of right proximal superficial femoral artery. He was started on heparin drip, switched to apixaban on hospital day 5, and discharged on hospital day 8. DISCUSSION: The risk of venous thromboembolism is quite high in elderly adults with UC. The literature suggests that thrombosis and hypercoagulability are features of IBD involved in the occurrence of thromboembolic events. Therefore, it is imperative to consider IBD as a differential diagnosis in elderly patients presenting with unprovoked thromboembolism and gastrointestinal bleeding.Figure 1.: Mural thrombus of the distal abdominal aorta and high-grade left iliac artery occlusion.Figure 2.: Colitis up to the descending colon.

Sarcoma de Kaposi clásico con compromiso gastrointestinal multifocal. Reporte de un caso

Although intestinal involvement occurs in more than half of the cases with KS that are HIV positive, it is uncommon in the classical form, as it occurs in approximately 10% of the patients. We present the case of a 60-year-old male patient with a one-year disease time characterized by having violaceous lesions on the feet and the hands, slightly pruritic and 2 months of epigastralgia and constipation with weight loss of approximately 12 percent of his total body weight. In the physical examination multiple violaceous papule-like lesions are shown on the hands and the feet, some coalescing to form plaques. Laboratory tests revealed a mild normocytic normocytic anemia, the serology for viral hepatitis B and C was negative, HIV negative and ELISA test too. An upper endoscopy was performed and multiple maculopapular and erythematous-violaceous lesions were observed in the esophagus, the stomach and the duodenum. In the colonoscopy, multiple lesions with similar characteristics in the ileum, throughout the colon and in the rectum were recognized. The biopsy result was compatible with the KS in all lesions and it was confirmed with the positive HVV-8 immunohistochemistry. This case highlights the likelihood of presenting GI SK in elderly patients with gastrointestinal compromise and cutaneous findings, HIV negatives as well as the need to realize an adequate discarding by performing endoscopic studies with the biopsies to optimize treatment.

Síndrome ascítica em Melopsittacus undulatus (Shaw, 1805) devido à hipoproteinemia por nutrição deficiente

The present study aimed to describe the first report of ascetic syndrome in poultry due to deficient nutrition hypoproteinemia, seeking to present data on the patient's history, care, diagnostic methods and treatments performed. At the Veterinary Hospital Veterinário Professor Ivon Macêdo Tabosa of the Federal University of Campina Grande, a specimen of Melopsittacus undulatus presented a large increase in volume in the abdominal region with a floating aspect for approximately six days. First, the bird was evaluated clinically, then it was subjected to imaging and laboratory tests (blood count and biochemistry). The performance of imaging exams has made it possible to rule out several causes, such as egg retention, neoplasms, peritonitis, among others. In addition, the anamnesis detected a history of food composed of a diet with sunflower seeds and rice straw. After evaluating the results of the blood count and biochemistry, a picture of mild hypoproteinemia and normocytic normocytic anemia was found. As treatment, aspiration of ascetic fluid was carried out and a change of diet to an extruded diet. After 15 days, the animal was again evaluated, showing to be active and without a picture of ascetic syndrome associated with a picture of hypoproteinemia, with clinical improvement after changing the seed diet for a formulated diet.

Bilateral Hip Pain - Soccer Player

HISTORY: A 16-year-old Asian male presented with 2 weeks of worsening groin pain. Pain began after a difficult soccer practice, without a specific inciting injury. Patient was evaluated by team’s athletic trainer and was referred to orthopedic surgery where x-rays were negative. One week later, patient presented to local pediatric emergency center with intermittent fevers, worsening pain and inability to ambulate. He denied any recent travel outside the US or new exposures. PHYSICAL EXAM: afebrile in no acute distress with tenderness to palpation over paraspinal muscles, costovertebral processes L3-L4 and quadriceps musculature. Patient walked with antalgic gait and found to have 2/5 strength hip flexion bilaterally with 5/5 strength in all other muscle groups. Cardiac, pulmonary and abdominal exam were unremarkable. There was no lymphadenopathy present on exam. DIFFERENTIAL DIAGNOSIS: 1. Ankylosing Spondylitis 2. Illiopsoas Abscess 3. Epidural abscess 4. Osteomyelitis 5. Malignancy TEST AND RESULTS: -ESR: elevated at 94 mm/hr, CRP: elevated at 4.57 mg/dL -CBC: mild normocytic anemia without leukocytosis or thrombocytopenia -CK, CMP, Uric Acid, LDH within normal limits -Blood culture: negative -Rheumatologic studies: ANA, adolase, ANCA were negative -Testicular US: negative -MRI of lumbar spine and pelvis: signal enhancement within the bones of pubis symphisis with significant surrounding soft tissue edema -Bone biopsy: focally degenerated bone, mixed chronic inflammation, fibrosis with reactive changes. No microorganisms present on special stains -Bone aerobic/anaerobic cultures: negative -Quantiferon gold: POSITIVE, mycobacterium sputum PCR: POSITIVE -Chest x-ray: negative FINAL/WORKING DIAGNOSIS: Tuberculosis osteomyelitis of the pelvis TREATMENT AND OUTCOMES: 1. Treatment with ethambutol, isoniazid, pyrazinamide, and rifampin daily until cleared by infectious disease 2. Close follow up with Infectious disease clinic with monitoring labs every 2 weeks 3. Indomethacin PRN for pain 4. Range of motion and strengthening exercises for bilateral hip flexors with physical therapy 5. Regular follow up with local department of health

Bilateral Hip Pain - Soccer Player

HISTORY: A 16-year-old Asian male presented with 2 weeks of worsening groin pain. Pain began after a difficult soccer practice, without a specific inciting injury. Patient was evaluated by team’s athletic trainer and was referred to orthopedic surgery where x-rays were negative. One week later, patient presented to local pediatric emergency center with intermittent fevers, worsening pain and inability to ambulate. He denied any recent travel outside the US or new exposures. PHYSICAL EXAM: afebrile in no acute distress with tenderness to palpation over paraspinal muscles, costovertebral processes L3-L4 and quadriceps musculature. Patient walked with antalgic gait and found to have 2/5 strength hip flexion bilaterally with 5/5 strength in all other muscle groups. Cardiac, pulmonary and abdominal exam were unremarkable. There was no lymphadenopathy present on exam. DIFFERENTIAL DIAGNOSIS: 1. Ankylosing Spondylitis 2. Illiopsoas Abscess 3. Epidural abscess 4. Osteomyelitis 5. Malignancy TEST AND RESULTS: -ESR: elevated at 94 mm/hr, CRP: elevated at 4.57 mg/dL -CBC: mild normocytic anemia without leukocytosis or thrombocytopenia -CK, CMP, Uric Acid, LDH within normal limits -Blood culture: negative -Rheumatologic studies: ANA, adolase, ANCA were negative -Testicular US: negative -MRI of lumbar spine and pelvis: signal enhancement within the bones of pubis symphisis with significant surrounding soft tissue edema -Bone biopsy: focally degenerated bone, mixed chronic inflammation, fibrosis with reactive changes. No microorganisms present on special stains -Bone aerobic/anaerobic cultures: negative -Quantiferon gold: POSITIVE, mycobacterium sputum PCR: POSITIVE -Chest x-ray: negative FINAL/WORKING DIAGNOSIS: Tuberculosis osteomyelitis of the pelvis TREATMENT AND OUTCOMES: 1. Treatment with ethambutol, isoniazid, pyrazinamide, and rifampin daily until cleared by infectious disease 2. Close follow up with Infectious disease clinic with monitoring labs every 2 weeks 3. Indomethacin PRN for pain 4. Range of motion and strengthening exercises for bilateral hip flexors with physical therapy 5. Regular follow up with local department of health

3082 Overdosing From Down Under: An Atypical Route of Methamphetamine Use Resulting in Bowel Ischemia

INTRODUCTION: Methamphetamines are sympathomimetic medications that cause a surge in catecholamines, which leads to a significant abuse potential. The National Survey on Drug Use and Health reported in 2017 that 5.4% of the population, which at that time made up over 14.7 million people have used methamphetamines at least once in their lives. The usual routes of administration include oral, nasal or intravenous. However, novel anal routes are being seen in current literature and clinicians should be aware so they can notice the severe and potentially life threatening side effects. CASE DESCRIPTION/METHODS: The case involves a 29-year-old male with history of benzodiazepine and methamphetamine use who came to the hospital with complaints of rectal pain and hematochezia. He reported continued daily intravenous drug use but also divulged that he had been inserting methamphetamines rectally for the past 5 days. He reported that recently, the bag burst and caused him significant hemorroidal irritation and bleeding. Most of the drugs passed rectally per the patient and the bleeding was improving by the time of admission. Vitals were stable and labs were significant for mild leukocytosis, mild normocytic anemia, and a urine drug test showed elevated amphetamines and benzodiazepines. Due to the continued hematochezia, gastroenterology was consulted and a flexible sigmoidoscopy showed distal ischemic changes in the rectum and an anal ulcer that showed chronic inflammation on biopsy. Through the hospital course, his symptoms improved and he was eventually discharged after extensive education and two weeks of rectal mesalamine. DISCUSSION: This case highlights two important points. The first deals with the unusual route of administration, which is helpful to know so that providers can address proper removal of the source. Methamphetamines have rapid gastrointestinal absorption, so it would be important to evacuate the rectal area to prevent further intoxication. The second key aspect of this case deals with the resulting side effect of bowel ischemia. A handful of case reports describe this adverse effect and patients range from having fatal to self-limited outcomes. However, these cases do not all address the route of drug ingestion but direct anal exposure would likely increase the risk of bowel ischemia due to the local vasocontrictive mechanism. Thus, it is vital to initially ask how patients administered the methamphetamines and evaluate the patient's clinical course for bowel injury secondary to ischemia.

1714 A Case of a Primary Large Cell Neuroendocrine Carcinoma of the Esophagus Disguised as a Food Impaction

INTRODUCTION: Neuroendocrine carcinomas (NECs) are defined epithelial neoplasms with predominant neuroendocrine differentiation. They primarily arise from the gut and bronchopulmonary systems with the possibility of distant metastasis. We present a case of an esophageal neuroendocrine neoplasm with unique endoscopic/radiographic features on presentation disguised as a food impaction. CASE DESCRIPTION/METHODS: A 50-year-old Caucasian male with past medical history of tobacco dependence; presented to the ED with complaints of solid food dysphagia for 1.5 months with unintentional weight loss of 15 lbs and intractable hiccups. On arrival, he was hemodynamically stable. Physical exam was unremarkable. Laboratory testing revealed mild normocytic anemia of 12.3, otherwise unremarkable. An upper endoscopy was performed revealing a large amount of meat in the mid-esophagus; however, after further manipulation there appeared to be bleeding from the mucosa (Figure 1). Upon closer inspection, a mass originating from the lateral esophageal wall was caked with food debris giving it the appearance of meat. CT Chest was performed showing a large heterogenous esophageal mass (8.1 cm v 5.7 cm) extending from the mid-esophagus to the GE junction with no evidence of direct invasion (Figure 2). Biopsies returned positive for large cell neuro-endocrine carcinoma with diffuse synaptophysin and Ki67 positivity. PET-CT performed as outpatient showed prominent peri-gastric lymphadenopathy. EUS was attempted but failed due to inability to pass the ultrasound scope. CT surgery subsequently performed a McKeown transthoracic esophagectomy for definitive therapy as outpatient. He recovered well from the procedure with positive radial margins and lymph nodes on pathology and is now undergoing adjuvant radiation and chemotherapy. DISCUSSION: Esophageal NEC is a rare entity with a generally dismal prognosis when high-grade. A study out of a large volume, tertiary center reported approximately 40 cases over a 20-year period. Given the sparsity of esophageal NECs, most studies are retrospective case series and are from outside the USA. It is reported that esophageal NECs represent only 0.4-1.4% of the gastrointestinal NECs a majority of which arise from the mid-esophagus. To our knowledge, there is no reports of a single case with similar endoscopic and radiographic findings which makes it unique. There is also limited data reported on the endoscopic/phenotypic appearance of large cell neuroendocrine carcinomas of the esophagus.

Zator płucny i guz lewego przedsionka u pacjentki z nowotworem płuca — trudności diagnostyczno-terapeutyczne

A 64 year-old female with a history of hypertension and chronic obstructive pulmonary disease after radical treatment (radiotherapy and chemotherapy) of squamous cell carcinoma of the right lung in 2016, was admitted to the Depart- ment of Cardiology due to pulmonary embolism, confirmed in an angio-CT. Moreover, cancer recurrence on the right lung and a mass spreading through the right upper pulmonary vein to the left atrium (LA) that might be considered to be a thrombus, were demonstrated. The patient, for the week before admission, had suffered from exercise dyspnoea, pain in the lower limbs, and syncope. On admission, the patient presented in a serious general condition. In laboratory tests, elevated D-dimer and NT-proBNP (450 pg/ml) concentrations as well as mild normocytic anaemia were revealed. Echocardiography showed preserved systolic (ejection fraction = 55%) and impaired diastolic left ventricle function, without signs of valvular heart disease. In transoesophageal echocardiography (TEE) in the LA an additional echo of 18 × 12 mm, spreading through the right upper pulmonary vein that might be considered to be a thrombus was revealed. However, due to the location of neo- plastic lesions in the right lung, a cancerous tumour spreading throughout could not be excluded. An abdominal and pelvis CT did not reveal any metastasis. Low molecular weight heparin in a therapeutic dose and acetylsalicylic acid were incorporated into the therapy. A mul- tidisciplinary consultation (oncologist, cardiac surgeon, cardiologist, anaesthesiologist) was conducted and the mass in the LA was initially qualified for surgical resection. Prior to surgery, spirometry and the exclusion of thromboembolic material in the lower limb veins were required. Spirometry demonstrated moderate bronchial obstruction. In ultrasound of the lower limb, deep vein thrombosis was excluded, but a few hypoechal nodules in the shank muscles of the right lower limb were visualised. A suspicion of metastases was confirmed using angio-CT. In the TEE performed after five days of low molecular weight heparin therapy, the previously described mass in the LA reduced its echogenicity and dimensions (to 10 × 8 mm). The patient’s general condition improved slightly. The patient was re-consulted by the cardiac surgeon and, due to presence of distant metastases, was disqualified from surgery. Another oncologist consultation was performed, and further diagnostic and therapeutic aims were established. The therapeutic dose of heparin was maintained.

A Rare Case of High-Grade Metastatic Cystic Pancreatic Neuroendocrine Tumor

A 63-year-old female with a history of nicotine dependence and new-onset poorly controlled diabetes mellitus presented with nausea, vomiting, fatigue and progressive unintentional weight loss for 6 months. She did not report any fever, night sweats, abdominal pain, gastrointestinal bleeding or recent change in bowel habits. Initially her symptoms were attributed to poorly controlled diabetes. Consequently, due to persistent symptoms laboratory evaluation was performed, which showed mild normocytic anemia and minimally elevated ALT to 49 U/L. A liver ultrasound was obtained which demonstrated multiple lesions within the liver that were predominantly cystic but with some solid components, with the largest lesion measuring 3.1 x 3.9 x 3.6 cm. A subsequent colonoscopy was unremarkable and CT of the abdomen and pelvis revealed a large 5.7 x 4.5 cm cystic mass in the tail of pancreas abutting the gastric wall in addition to multiple low attenuating lesions of the liver that were predominantly cystic with minimal peripheral enhancement (Figure 1). She underwent liver biopsy which demonstrated a well to moderately differentiated pancreatic neuroendocrine neoplasm (positive for chromogranin, synaptophysin, and Islet1 while negative for PAX8, Ki67 of 24%). Overall, pancreatic neuroendocrine tumors (PNETs) are uncommon with an incidence of approximately ˜0.5 per 100,000 annually, and cystic tumors are rarer, comprising approximately 10% of all PNETs. In comparison to solid PNETs, cystic tumors are less likely to be locally invasive or metastatic, are less likely to be functional and generally have a lower proliferation rate1,2. Cystic tumors are also less likely to be part of a multiple neuroendocrine neoplasia syndrome. In fact, purely cystic tumors are generally regarded as indolent, however, this case is an exception to that rule.1279_A.tif Figure 1: CT abdomen and pelvis with contrast demonstrating a cystic mass in the tail of pancreas along with multiple cystic masses in the liver.

Exceptional microorganisms on blood smear.

A 67-year-old woman with metastatic pancreatic adenocarcinoma was referred for acute respiratory distress syndrome and severe sepsis. She had a totally implantable central venous access device for chemotherapy administration and home parenteral nutrition. Laboratory workup at admission revealed increased C-reactive protein (209 mg/L), mild normocytic anemia (hemoglobin 8.6 g/dL), and severe acute thrombocytopenia (platelet count 3 × 109/L, as compared to 257 × 109/L 8 days before). White blood cell count, absolute neutrophil count, and blood smear were normal. Laboratory tests excluded disseminated intravascular coagulation. The patient was treated with cefotaxime and metronidazole. Forty-eight hours later, blood smear examination done on a sample taken through the intravenous line revealed yeasts (Image 1, panels A-E-B-D). Moreover, some bacilli were also observed (Image 1, panels C-E). Yeasts and budding yeasts in monocyte and neutrophil cytoplasm, extracellular branching pseudohyphae (arrow, respectively panels A-E-B-D May–Grünwald–Giemsa stain, original magnification 100× and 20×). Extra- and intracellular bacilli (arrowhead, respectively panels C-E, May–Grünwald–Giemsa stain, original magnification 100×) This exceptional observation of microorganisms on blood smear led to microbiological tests, identifying Candida albicans and Klebsiella pneumoniae. Severe thrombocytopenia was most likely related to severe sepsis. The patient was admitted to a palliative care unit. Nothing to report.

Strongyloidiasis: An Incidental Discovery on Colonoscopy in an Asymptomatic Immunocompromised Host

Strongyloidiasis can range from asymptomatic eosinophilia in an immunocompetent host to disseminated disease with septic shock in an immunocompromised host. In this case, we present the incidental finding on routine colonoscopy of strongyloidiasis in an immunocompromised host. A seventy-one year-old gentleman with past medical history notable for Chronic Lymphocytic Leukemia on therapy with imatinib presented for an esophagogastroduodenoscopy (EGD) and colonoscopy for evaluation of intermittent solid food dysphagia, weight loss, and normocytic anemia. He denied any odynophagia, abdominal pain, diarrhea, constipation, hematochezia, or melena. Physical examination was normal and cursory review of the laboratory data revealed only a mild normocytic anemia. EGD was normal. Colonoscopy revealed severe pandiverticulosis and in the ascending colon, a small (< 1cm) raised sessile lesion was encountered with an odd appearance to it. It did not have the classic pattern of either a tubular or sessile serrated adenoma when examined under white light (Image 1) or narrow band imaging (Image 2). The lesion did not evert when poked by the biopsy forceps, making an inverted diverticulum unlikely. Snare cautery polypectomy was performed and later to our surprise, the pathology returned back as it being an eosinophilic abscess with numerous strongyloides organisms present (Image 3) Upon further review of the patient's chart, it was noted that he had peripheral eosinophilia for years but this had gone largely unnoticed. The patient received anti-helminthic therapy with ivermectin and did well with complete resolution of his peripheral eosinophilia over time. The most common manifestations of strongyloidiasis are mild waxing and waning gastrointestinal (i.e. diarrhea), cutaneous (i.e. rash, pruritus), or pulmonary symptoms (i.e. cough, dyspnea) that can persist for years. More often than not, patients are asymptomatic and the presence of peripheral eosinophilia is the only marker to suggest a parasitic infection. In addition, as in our case, there are no classic endoscopic features of strongyloidiasis and it can mimic that of other diseases. Overall the prognosis of strongyloidiasis is good if detected early and treated appropriately. It is especially important to be worried about infection in immunocompromised individuals given they are at risk for developing a potentially fatal hyperinfection syndrome that can result in multi-organ failure and death.Figure: Image 1- White Light View of Lesion.Figure: Image 1- Narrow Band Imaging View of Lesion.Figure: Image 3- Strongyloides filariform larvae seen in upper left portion of slide with surrounding eosinophilia.

Incidental Discovery of Early Strongyloides stercoralis Colitis in an Active Duty Service Member

Strongyloides stercoralis is a potentially lethal parasitic infection with a broad range of clinical and endoscopic manifestations. While hyperinfection can result in dramatic colonoscopic findings that mimic ulcerative colitis, asymptomatic patients may exhibit more subtle findings such as erythema or nonspecific white lesions. A 43-year-old Nigerian born woman was referred to the gastroenterology clinic for workup of longstanding constipation. She reported onset related to her uncomplicated spontaneous vaginal deliveries. Varied laxative use yielded no improvement. The patient denied weight loss, fatigue, tenesmus, urgency, or incomplete evacuation. Travel history was remarkable for recent travel to Nigeria and annual vacations in Belize. Abdominal exam was unremarkable. A rectal exam revealed a palpable mass in the left lateral rectal wall. Laboratory evaluation was notable for a mild normocytic anemia and peripheral eosinophilia. Computed tomography of the pelvis with contrast revealed retroversion of the uterus with suggestion of mass effect on the rectum and sigmoid colon. Defacography confirmed mild uterine prolapse and a small rectocele. A subsequent optical colonoscopy revealed grossly normal colonic mucosa, with exception of external hemorrhoids and punctate white papules in the proximal right colon. Biopsy and histologic examination of the lesions revealed colonic mucosa with eosinophilic infiltrate and filariform S. stercoralis larva. The patient was subsequently treated with ivermectin, and referred to urogynecology for pelvic floor physical therapy. This case illustrates subtle colonoscopic findings of S. stercoralis colitis. Endoscopy in foreign born patients with a history of exotic travel requires a high index of suspicion for diagnosis of parasitic infections. In this case, the burden of parasitic disease was unlikely a prime contributor to her presenting symptom profile; however, the biopsy of suspicious lesions led to an early diagnosis of a potentially life threatening infection. Recognition of the more subtle colonoscopic findings is key to early diagnosis and treatment to prevent significant morbidity and mortality.Figure

Late-Onset Biallelic Mismatch Repair Deficiency Syndrome

A 33-year-old man with a history of successfully treated low-grade follicular lymphoma 2-years prior was evaluated for recurrent aching upper abdominal pain, early satiety, and fatigue. He denied overt gastrointestinal bleeding, but reported occasional night sweats, chills, and weight loss. His family history was notable for esophageal cancer in his father and gastric cancer in his mother. Physical examination showed 2 café-au-lait macules on the lower abdomen but no lymphadenopathy, abdominal tenderness, or mass was appreciated. Laboratory tests showed mild normocytic anemia and normal liver enzyme levels. An abdominal computed tomographic (CT) enterography showed bowel-wall thickening and luminal narrowing extending over the proximal jejunum (Figure A, arrow). Positron emission tomography showed corresponding activity, highlighting the small bowel as the primary source (Figure B). A CT-guided biopsy showed metastatic adenocarcinoma of an unknown primary favoring a gastrointestinal source. Upper endoscopy was unremarkable. Colonoscopy showed multiple large adenomas in the proximal colon (Figure C). The patient underwent small-bowel surgical excision. Histologic examination of the specimen showed a biphasic tumor containing both mucinous and gland-forming parts (Figure D, top, H&E). Immunohistochemistry testing of the adenocarcinoma showed intact MLH1, MSH2, and PMS2 nuclear staining but abnormal (absent) MSH6 nuclear staining in both normal and tumor mucosa (Figure D, bottom). The diagnosis of biallelic mismatch repair deficiency (BMMRD) syndrome (also known as constitutional mismatch repair deficiency) was made, which is a rare autosomal-recessive hereditary cancer syndrome that results from biallelic germline mutations in 1 of the 4 mismatch repair genes: MLH1, MSH2, MSH6, and PMS2. The combination of café-au-lait macules, small-bowel adenocarcinoma, adenomatous colon polyps, and a history of lymphoma was highly suggestive of BMMRD. The absence of MSH6 expression in the tumor and normal tissue indicated biallelic MSH6 mutations. The tumor spectrum of BMMRD is broad, including hematologic, brain, and gastrointestinal tract tumors.1Wimmer K. Kratz C.P. Vasen H.F. et al.Diagnostic criteria for constitutional mismatch repair deficiency syndrome: suggestions of the European consortium ‘care for CMMRD' (C4CMMRD).J Med Genet. 2014; 51: 355-365Google Scholar These individuals often have dermatologic findings of neurofibromatosis type 1, such as café-au-lait macules. Although most often a childhood cancer syndrome, BMMRD has a less-penetrant phenotype in which individuals remain unaffected until the third or fourth decade of life (as in our patient). In addition, tumor immunohistochemistry testing often is difficult to interpret in BMMRD cases because the control (normal tissue) has absent MMR staining. Unlike the autosomal-dominant mutation of a MMR gene in Lynch syndrome, BMMRD is much less understood.2Vasen H. Ghorbanoghli Z. Bourdeaut F. et al.Guidelines for surveillance of individuals with constitutional mismatch repair-deficiency proposed by the European Consortium ‘Care for CMMR-D’(C4CMMR-D).J Med Genet. 2014; 51: 283-293Google Scholar, 3Durno C. Boland C.R. Cohen S. et al.Recommendations on surveillance and management of Biallelic Mismatch Repair Deficiency (BMMRD) syndrome: a consensus statement by the US Multi-Society Task Force on colorectal cancer.Gastroenterology. 2017; 152: 1605-1614Google Scholar Although BMMRD recommendations for screening young persons have been formulated, the surveillance and tumor spectrum in adults remains less clear.3Durno C. Boland C.R. Cohen S. et al.Recommendations on surveillance and management of Biallelic Mismatch Repair Deficiency (BMMRD) syndrome: a consensus statement by the US Multi-Society Task Force on colorectal cancer.Gastroenterology. 2017; 152: 1605-1614Google Scholar This case illustrates several important points. First, one should maintain a high suspicion for hereditary cancer syndromes. Second, the finding of café-au-lait macules can be an important clue to BMMRD. Third, BMMRD has a broad tumor spectrum that includes multiple polyps and should be in the differential diagnosis of colonic adenomatous polyposis. Finally, the syndrome most often presents in childhood but may have a late-onset presentation, highlighting the need for increased awareness of this condition by adult gastroenterologists.

Intoxicação natural por Senecio brasiliensis em equinos

RESUMO: Intoxicações por plantas do gênero Senecio representam uma importante causa de morte em animais de produção, sendo Senecio brasiliensis a espécie mais envolvida nos casos de intoxicação espontânea. Nesse trabalho, são descritos os aspectos epidemiológicos, clínicos e anatomopatológicos de um surto de intoxicação natural por Senecio brasiliensis em equinos. Dois equinos, de um total de dezoito, foram afetados. Os casos ocorreram em uma propriedade rural no município de São Martinho da Serra, Rio Grande do Sul, Brasil. Grande quantidade de exemplares de Senecio brasiliensis em estágio de brotação foi encontrada na área onde os equinos estavam. Os animais eram da raça Crioula, sendo uma égua com quatro anos e um potro com cinco meses. A égua apresentou evolução aguda da doença com duração de três dias e o potro evolução crônica de dois meses. As principais manifestações clínicas observadas em ambos os equinos incluíam apatia, anorexia, emagrecimento, desidratação e sinais neurológicos. Além disso, havia moderado edema subcutâneo na região ventral do abdômen e marcada icterícia nas mucosas ocular, oral e vulvar da égua e palidez das mucosas no potro. Na avaliação bioquímica do potro, havia acentuado aumento da atividade sérica da gamaglutamil transferase (119 U/L), aumento da fosfatase alcalina (434 U/L) e hipoalbuminemia (2,1g/dL). No hemograma do mesmo, observou-se leve anemia normocítica e normocrômica (30% de hematócrito; VCM: 39,5 fL; HCM: 15,3pg). As alterações presentes em ambas as necropsias foram observadas principalmente no fígado, que estava difusamente aumentado de tamanho, escuro e firme. Na superfície de corte, observaram-se acentuação do padrão lobular e hemorragia. Histologicamente, no fígado dos equinos, havia graus variados de necrose coagulativa, hemorragia, fibrose, proliferação de ductos biliares, hepatomegalocitose e bilestase. Nas diferentes seções analisadas do encéfalo, havia alterações astrocitárias restritas à substância cinzenta, predominantemente, no córtex telencefálico. Os astrócitos degenerados eram similares aos astrócitos de Alzheimer tipo II. O diagnóstico da intoxicação nesses casos foi baseado na epidemiologia, no quadro clínico, nas lesões de necropsia e nos achados histopatológicos. Cabe ressaltar que a necrose de coagulação e a discreta fibrose e proliferação de ductos biliares observados na égua, constituiu uma apresentação subaguda da intoxicação, enquanto que a fibrose, mais predominante no potro, caracterizou uma hepatopatia crônica.

Impact of TET2 deficiency on iron metabolism in erythroblasts.

Sideroblastic anemia is characterized by the presence of ring sideroblasts (RSs), which are caused by iron accumulation in the mitochondria of erythroblasts and are present in both the acquired and congenital forms of the disease. However, the mechanism leading to RS formationremains elusive. Acquired sideroblastic anemia is usually observed in myelodysplastic syndrome (MDS). Because a subset of MDS harbors a somatic mutation of TET2, it may be involved in iron metabolism and/or heme biosynthesis in erythroblasts. Tet2 knockdown (Tet2trap) induced exhibited mild normocytic anemia and elevated serum ferritin levels in 4-month-old mice. Although typical RSs were not observed, increased mitochondrial ferritin (FTMT) amounts were observed in the erythroblasts of Tet2-knockdown mice. Quantitative real-time polymerase chain reaction demonstrated significant dysregulation of genes involved in iron and heme metabolism, including Hmox1, Fech, Abcb7, and Sf3b1 downregulation. After the identification of a cytosine-guanine island in the promoters of Fech, Abcb7, and Sf3b1, we evaluated DNA methylation status and found significantly higher methylation levels at the CpG sites in the erythroblasts of Tet2-knockdown mice. Furthermore, Tet2 knockdown in erythroblasts resulted in decreased heme concentration and accumulation of FTMT. Therefore, TET2 plays a role in the iron and heme metabolism in erythroblasts.

Neospora caninum oocyst shedding in a naturally infected dog from Italy.

Although the seroprevalence of Neospora caninum infection in dogs can be relatively high, there are few reports of dogs naturally shedding N. caninum oocysts. Worldwide, the prevalence of Neospora excretion in canine faeces ranges from 0.03% to 4.9%. A mixed-breed male household dog of about 8years in age living in the district of Pisa (Tuscany, Central Italy) was referred for dysorexia, weakness and general lymph node enlargement. Clinical pathology demonstrated mild normocytic and normochromic anemia, thrombocytopenia and hypoproteinemia with hypoalbuminemia. Serology for Leishmania, Ehrlichia canis and Anaplasma phagocytophilum was negative. From lymph node and bone marrow analysis, T cell lymphoma, high grade, pleomorphic type, clinical stage V, was diagnosed. The dog was treated with a chemotherapy induction protocol with vincristine, cyclophosphamide, and prednisone for 8weeks. A faecal sample collected from the dog 7days after the beginning of the treatment and analysed by flotation test and a McMaster method, revealed the presence of 300 OPG N. caninum-like unsporulated oocysts of about 10-11μm in diameter. An aliquot of the same faecal sample analysed by PCR with species-specific primer pairs Np6+/Np21+ was positive for N. caninum DNA, while specific serology performed on sera collected at the first visit and a month later by IFAT, were positive with a titer of 1: 50 and 1:400, respectively. Soon after the dog died. Naturally occurring systemic illness or iatrogenic immunosuppression may predispose dogs to proliferation of the parasite. The dog was receiving chemo-immunosuppressive treatment for T cell lymphoma. For this reason it is possible to suppose that emission of Neospora oocysts in this dog was caused by reactivation of a latent infection.

Paraganglioma of the organ of Zuckerkandl associated with a somatic HIF2α mutation: A case report.

Paragangliomas of the organ of Zuckerkandl (OZ-PGL) are rare tumors that, in >70% of cases, occur in association with succinate dehydrogenase complex iron sulfur subunit B (SDHB) or SDHD gene mutations. The aim of the current study was to determine whether a somatic genetic defect in the hypoxia-inducible factor 2α (HIF2α) gene was present in a case of sporadic OZ-PGL. A 32-year-old African female presented with uncontrolled hypertension during the first trimester of pregnancy. A diagnostic hysteroscopy was performed 3 months after delivery, precipitating a hypertensive crisis. Thereafter, the patient was diagnosed with noradrenaline-secreting OZ-PGL. A complete blood count identified mild normocytic anemia of an inflammatory origin. Surgical removal of the tumor resulted in normalization of plasma and urinary normetanephrine levels. Genetic testing for germline mutations (including large deletions) in the von Hippel-Lindau tumor suppressor, SDHB, SDHC and SDHD genes was normal. However, a heterozygous missense mutation (c.1589Cys>Tyr) was detected in exon 12 of HIF2α, which results in a substitution of alanine 530 with valine (Ala530Val) in the HIF2α protein. A germline mutation was excluded based on the negative results of blood DNA testing. A three-dimensional homology model of Ala530Val was constructed, which showed impaired HIF2α/VHL interaction and decreased HIF2α ubiquitination. 1H-high-resolution magic-angle-spinning nuclear magnetic resonance spectroscopy detected low succinate levels and high α and β glucose levels. To the best of our knowledge, the present case represents the first of its kind to associate a somatic HIF2α gain-of-function mutation with OZ-PGL. It is therefore recommended that patients without germline SDHx mutations should be tested for HIF2α mutations.

CD5-Negative Mantle Cell Leukemia Shows Frequent 17p Deletion and Marrow Involvement Mimicking Marginal Zone Lymphoma

Introduction: Mantle cell lymphoma is characterized by the t(11;14)(q13;q32) and can usually be recognized by its typical CD5+/CD23- immunophenotype. However, phenotypic variations have been observed and such variants can resemble other types of B-cell neoplasms, including chronic lymphocytic leukemia (CLL/SLL) and marginal zone lymphoma. In particular, the CD5- variant is diagnostically challenging. Some CD5- mantle cell lymphomas have been reported to have an indolent clinical course, while others follow an aggressive course similar to typical mantle cell lymphoma. To our knowledge, CD5- mantle cell leukemia has not been fully characterized. To further our understanding of this disease entity for diagnostic workup and risk assessment, we evaluated clinical, morphologic, immunophenotypic, and genetic features in a cohort of CD5- mantle cell leukemia.Methods: Among 111 cases of mantle cell leukemia identified from our database over a 2-year period, 12 were CD5- with t(11;14) and absolute peripheral lymphocytosis (>5,000/uL). Antigen expression was defined by flow cytometry as positive, dim positive, or negative. Conventional chromosome analysis and FISH were performed on all cases, including probes for 11q22.3 (ATM), 12 (CEP 12), 13q14, 13q34, 17p13 (TP53) and t(11;14) (IGH-CCND1). Other parameters obtained included age, gender, CBC, blood and bone marrow histology, and IgVH mutational status.Results: Of the 12 patients, 7 were female with a median age of 67 years (range: 55-88 years). Patients presented with marked lymphocytosis (mean: 55 K/uL) and mild normocytic anemia (mean: 11.3 g/dL). The average platelet count was within the low normal range (mean: 173 K/uL). Flow cytometric analysis showed that all cases expressed CD19 and surface light chain restriction (10 kappa and 2 lambda), and lacked CD5 and CD10. All except one case expressed CD20. CD23 was negative in 8 cases and dim positive in 4 cases. Thus, the leukemic phenotype was suggestive of a marginal zone lymphoma. Morphologically, the leukemic cells were small to medium sized with round nuclei and scant to moderately abundant cytoplasm. Bone marrow biopsy was performed in 6 of 12 cases. All 6 cases showed marrow involvement (mean: 45%; range: 25-85%) with interstitial and intrasinusoidal distribution patterns. While the marrow histology was suggestive of involvement by marginal zone lymphoma, immunohistochemical testing for cyclin D1 revealed positive nuclear staining in the leukemic cells. FISH for t(11;14) was positive in all 12 cases. In contrast, conventional chromosome analysis detected t(11;14) in only 6 cases (3 blood and 3 marrow samples). Additional cytogenetic abnormalities were detected in 8 (67%) patients. Five (42%) cases showed 17p deletion. Other abnormalities included 13q- (3/12; 25%), 11q- (2/12; 17%), and trisomy 12 (1/12; 8%). IgVH analysis was performed in 2 cases, and both exhibited IgVH hypermutation.Conclusions: CD5- mantle cell leukemia comprised approximately 11% of mantle cell leukemia in our series. In addition to t(11;14), other chromosome abnormalities were identified in the majority of the cases (67%). Deletion of 17p was most frequent, likely representing a more aggressive form in contrast to the previously described indolent form. The leukemic immunophenotype and marrow infiltration features resembled marginal zone lymphoma, indicating the importance of detecting t(11;14) for proper classification and clinical management of the disease. We observed that FISH was much more sensitive in detecting t(11;14) than conventional chromosome analysis. Therefore, performing FISH for t(11;14) and 17p- would be useful for diagnostic workup of mature B-cell leukemia regardless of CD5 positivity. Our limited observation of IgVH hypermutation in CD5- mantle cell leukemia would suggest future studies to investigate this potential relationship for prognostic implications. DisclosuresNo relevant conflicts of interest to declare.

Lymph Node Primary Gastrinoma: A Case Report

Introduction: Zollinger-Ellison (ZE) syndrome is caused by gastrin-secreting tumors of neuroendocrine origin. Subsequent gastric acid hypersecretion leads to peptic ulcer disease, malabsorption and diarrhea. Here we present a rare case of a lymph node primary gastrinoma.Figure 1Figure 2Figure 3Case report: A previously healthy 55 y/o female presented with chronic heart burn and epigastric pain associated with diarrhea, intermittent melena and unintentional 100 pound weight-loss over 1 year. Proton pump inhibitors (PPI) and histamine receptor-2 blockers did not alleviate her symptoms. No family history of tumors were noted, including those related to multiple endocrine neoplasia type I (MEN-I, Wermer syndrome). Blood labs were normal other than mild normocytic anemia and hypoalbuminemia. Upper endoscopy showed LA grade B esophagitis, as well as multiple ulcers in the second and third portion of duodenum. CT scan did not show any abnormalities, including masses. Given clinical suspicion, gastrin and chromogranin A levels were measured, which were markedly elevated at 2341 pg/mL and 2737 ng/mg, respectively. Octreotide scan showed a foci of activity in the proximity of pancreatic head. Endoscopic ultrasound (EUS) showed a round, hypoechoic 1.3 cm lymph node near the pancreatic head that underwent fine needle aspiration (FNA). On cytology review of smears and cell block, there were monotonous bland cells that stained positive for gastrin, synaptophysin and chromogranin. Gastric fluid pH was measured at this time, while on twice daily oral PPI therapy, and was found to be 2. She then underwent exploratory laparotomy. She was found to have a peri-duodenal lymph node, which was resected and confirmed to have intranodal gastrinoma. No other masses or lesions were identified. There was resolution of her symptoms and hypergastrinemia to 87 pg/mL, and have remained stable for 7 months post-surgery. Discussion: ZE syndrome is a rare cause of hyper-gastrinemia that leads to acid hypersecretion. Typically when a lymph node is involved it represents metastatic disease; however, in this case report we present a rare case of lymph node primary gastrinoma. This is supported by clinical symptoms, EUS findings, correlating octreotide scan, hypergastrinemia with low gastric pH, and the subsequent surgical resection of a lymph node that resulted in the resolution of her symptoms and normalization of her labs.