Medical Image of the Week: Diffuse Gastric Bleeding and ALL

Figure 1. Technetium 99m tagged RBC scan showing abnormal radio tracer accumulation throughout the stomach (Panel A), and subsequently passing into the small bowel (Panel B).

A 26-year-old man with a medical history significant for acute lymphoblastic leukemia (ALL) presented with hypovolemic shock secondary to large volume hematemesis. The patient was diagnosed with ALL and treated with high dose chemotherapy followed by peripheral blood stem cell transplant from a matched unrelated donor one year prior to presentation. His treatment course was complicated by grade 4 acute graft versus host disease (GVHD) and CMV colitis. Blood work on admission showed hemoglobin of 6.4 g/dL and a leukocytosis. Patient was intubated for airway protection, transferred to ICU, and EGD was performed, which revealed diffusely friable mucosa, inflammation, and ulcerations throughout the gastric mucosa with only a few areas of normal appearing mucosa. Additionally, areas of spontaneous bleeding were seen. Selective arteriography within the right gastric and gastroduodenal arteries showed no active extravasation from the stomach or duodenum. However the gastroepiploic and right gastric arteries were prophylactically embolized. Subsequently, a technetium 99m tagged RBC scan demonstrated abnormal radio-tracer accumulation throughout the stomach with subsequent passage into the small bowel (Figure 1). The patient continued to have refractory gastric bleeding even with an increased dose of cyclosporine. Surgical measures including gastrectomy were discussed with the family. However, the family decided on comfort care. The patient died the following day.

Although gastric bleeding is rare in ALL patients in general, it is more commonly associated with certain condition such as GVHD and colitis following allogeneic stem cell transplantation (SCT). One of the retrospective studies with 447 SCT patients showed that 21.1% of study population experienced major GI bleeding, requiring transfusions or surgical intervention. Also, their mortality was shown to be twice higher than patients without bleeding complication, although most cases of bleeding were mild and occurred in the peri-transplant period with concurrent severe thrombocytopenia (1).

Hemorrhagic complications occur predominantly during the first month of post transplant, and bleeding is more commonly associated with allogeneic SCT compared to autologous SCT (2). This is mainly secondary to GVHD with gastrointestinal involvement, which leads to destruction and fragility of the epithelium as well as hyper-perfusion and proliferation of the blood vessels. As such, the risk of hemorrhage in patients with acute and chronic GVHD greater than grade I was 2.9 and 4.2 fold higher, respectively, and these patients had 10.8 fold higher risk of severe bleeding. The risk of bleeding is further increased by CMV infection, which infects vascular endothelial cells, narrows capillary lumens, and leads to ischemia and ulceration of gastric mucosa (3). The combination of GVHD and CMV infection could have synergistically damaged the gastric mucosa leading to severe refractory bleeding in our case.

Onyemaechi Okolo MD¹, Seongseok Yun MD PhD¹, Faiz Anwer MD, FACP²

¹Department of Medicine

²Department of Hematology & Oncology, Blood & Bone Marrow Transplantation Program

University of Arizona

Tucson, AZ, 85721

References

1. Pihusch R, Salat C, Schmidt E, Göhring P, Pihusch M, Hiller E, Holler E, Kolb HJ. Hemostatic complications in bone marrow transplantation: a retrospective analysis of 447 patients. Transplantation. 2002;74(9):1303-9. [CrossRef] [PubMed]
2. Törnebohm E, Lockner D, Paul C. A retrospective analysis of bleeding complications in 438 patients with acute leukaemia during the years 1972-1991. Eur J Haematol. 1993;50(3):160-7. [CrossRef] [PubMed]
3. Cheung AN, Ng IO. Cytomegalovirus infection of the gastrointestinal tract in non-AIDS patients. Am J Gastroenterol. 1993;88(11):1882-6. [PubMed]

Cite as: Okolo O, Yun S, Anwer F. Medical image of the week: diffuse gastric bleeding and ALL. Southwest J Pulm Crit Care. 2016;12(3):108-9. doi: http://dx.doi.org/10.13175/swjpcc010-16 PDF

Medical Image of the Week: CMV Cytopathic Effect

Figure 1. Cluster of 3 large cells, most likely infected type II pneumocytes, with a single prominent red stained nuclear inclusion surrounded by a clear halo. This appearance is the “cytopathic effect” needed to definitively diagnose active CMV infection.

Figure 2. Electron microscopy (8800x) of an infected cell showing  cytomegalovirus (CMV) virions within the nuclear inclusion (small black dots encircled).

Bronchoalveolar lavage (BAL) was performed on a 45-year old man with a history of treated mycosis fungoides and Sézary syndrome, who presented with fever and pulmonary infiltrates. BAL Papanicolaou stain (Figure 1, 400x) showed single cells (lymphocytes, arrows and alveolar macrophages, stars) and a small cluster of 3 large cells, most likely infected type II pneumocytes, with a single prominent red stained nuclear inclusion surrounded by a clear halo. Nuclear chromatin was marginated on the nuclear membrane creating this “owl’s eye” appearance. In vitro, infected cells show cytomegalovirus (CMV) virions within the nuclear inclusion (Figure 2, small black dots encircled, 8,800x)

The "owl's eye" appearance (Figure 1) is the “cytopathic effect” needed to definitively diagnose active CMV infection. While cells infected with adenovirus or herpesvirus may have nuclear inclusions, the cells typically are much smaller. CMV was cultured from the BAL, and no other pathogen was identified by cytology or culture. Quantitative PCR on blood for CMV was 144359 IU/ml.

Afshin Sam, MD; Felicia Goodrum, PhD; Robert Ricciotti, MD; Ken Knox, MD and Richard Sobonya, MD

Departments of Medicine, Immunobiology, and Pathology

University of Arizona Health Sciences Center

Tucson, AZ

Reference as: Sam A, Goodrum F, Ricciotti R, Knox KS, Sobonya R. Medical image of the week: CMV cytopathic effect. Southwest J Pulm Crit Care. 2014;9(6):341-2. doi: http://dx.doi.org/10.13175/swjpcc161-14 PDF

Medical Image of the Week: Cytomegalovirus Pneumonia

Figure 1. CT Chest, coronal cut showing left lower lobe consolidation.

Figure 2.  Pap stain highlights an enlarged cytomegalovirus-infected pneumocyte containing a single, dark intranuclear inclusion (arrow) with surrounding halo, giving the cell a characteristic “owl’s eye” appearance. Background cells consist of predominantly of macrophages and red blood cells (100x).

Figure 3. CMV-infected pneumocyte demonstrating an enlarged nucleus with a single dense intranuclear inclusion. The cytoplasm contains smaller basophilic inclusions with vacuolization and cytoplasmic projections (Pap stain, 100x).

A 29 year-old female with a history of systemic lupus erythematosus presented with a seven-day history of fever, dyspnea and a non-productive cough. She underwent renal transplantation four weeks prior to admission and was maintained on mycophenolate, tacrolimus, prednisone and prophylactic fluconazole, trimethoprim/sulfamethoxazole and valgangcyclovir. A CT chest was performed (Figure 1) and revealed left lower lobe consolidation. A BAL was performed in the left lower lobe and the cell count revealed 50% lymphocytes, 13% neutrophils and 37% macrophages. The BAL Papanicolaou stain showed enlarged cytomegalovirus-infected pneumocytes with the characteristic “owl’s eye” appearance (Figures 2 and 3). CMV quantitative PCR from serum resulted 648,615 IU/m.  The BAL culture grew CMV. The patient was started on treatment with valgangcyclovir with clinical improvement.

While often thought of as a “pneumonitis” with diffuse infiltrates, CMV can cause a lobar pneumonia in up to 30% of patients.  Prophylaxis is effective, but cases can occur despite a preemptive strategy.

Nathaniel Reyes MD^*, Julianna J. Weiel MSII⁺, Erika R. Bracamonte MD⁺, Linda Snyder MD^*
Department of Medicine, Division of Pulmonary and Critical Care Medicine*
Department of Pathology⁺

University of Arizona

Tucson, Arizona

Reference

Kang E, Patz E, Miller NL. Cytomegalovirus pneumonia in transplant patients: CT findings. J Comput Assisted Tomogr. 1998:20:295-9. [CrossRef]

Reference as: Reyes N, Weiel JJ, Bracamonte ER, Snyder L. Medical image of the week: cytomegalovirus pneumonia. Southwest J Pulm Crit Care. 2013;7(4):221-2. doi: http://dx.doi.org/10.13175/swjpcc131-13 PDF