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Infectious Disease Pathology
Tuesday, March 10, 7:30 PM
Convention Center 306
Clinical histories are printed below.
Click on the case numbers for text and references of each case.
Click on each slide thumbnail image for an enlarged view
Infection and Intracellular Structures
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Moderator:
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J. STEPHEN DUMLER
Johns Hopkins University School of Medicine, Baltimore, MD
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Disclosure:
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In accordance with ACCME guidelines regarding disclosure, the USCAP policy requires that faculty members who have a significant financial or other relationship with a commercial company, entity, or service (which will be discussed in this Symposium) must disclose this to attendees. The Academy also requires that speakers disclose any products that are not labeled for the use under discussion. J. Stephen Dumler is the patent holder for a method to propagate antigens for serological tests for A. phagocytophilum infection for which royalties are received. The other speakers listed below have indicated they have nothing to disclose.
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Panelists:
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STEPHEN D. ALLEN, Indiana University School of Medicine, Indianapolis, IN
JAN M. ORENSTEIN, G. Washington University. Med. Ctr., Washington, DC
J. STEPHEN DUMLER, The Johns Hopkins University School of Medicine, Baltimore, MD
SHERIF R. ZAKI, Centers/Disease Control, Atlanta, GA
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Clinical Histories and Still Images are displayed below.
Click on slide thumbnail images for an enlarged view.
If you have any difficulties viewing these slides, email or call George Clay at +1.724.449.1137.
for Text and References
Submitted by: Stephen D. Allen - Indiana University School of Medicine, Indianapolis, IN
A 43-year-old man was transferred from an outside hospital for further evaluation and management of abdominal pain. The patient had abdominal pain for approximately 10 days and the pain had been worsening. He noted difficulty in swallowing, and had a 30 pound unintentional weight loss. He also stated he had gotten surgery for hemorrhoids and "intestine hanging out of my anus" approximately three weeks ago. The patient noted tenesmus with significant straining to produce a bowel movement. Although he also gave a history of diarrhea in recent weeks, his last bowel movement was normal and occurred three days ago. He had occasional nausea, but no emesis. He denied any chills, but had been having high grade fevers. Otherwise, he denied any shortness of breath or chest pain. His abdominal pain was cramping and worse in his left lower quadrant and suprapubic regions. His past medical history was significant for AIDS with his last CD4 count two weeks ago of 10. In addition, the patient had been incarcerated in northern Indiana, and was a recovering narcotic and alcohol addict. He had immigrated to the US from Puerto Rico in 1998. The patient denied a history of opportunistic infection and tuberculosis. He denied HAART, but outside records indicated he was admitted on a regimen of emtricitabine, kaletra, lamivudine, levoquin and bactrim. On physical examination, his initial temperature in the emergency room was 105.5 F. He was a cachectic Latino man with a mildly toxic appearance. HEENT examination was unremarkable. Chest examination revealed rales bilaterally. His abdomen was soft, mildly distended, and moderately tender diffusely, greatest in the left lower quadrant and suprapubic regions. There was a 2 cm, mobile mass in his scrotum. Laboratory data was notable for a white blood count of 1.9 with 13% bandemia, hemoglobin 9.6, platelets 85 and AST 223 (H). Blood and urine cultures were pending. A chest x-ray demonstrated a large amount of free intraperitoneal air and a suspected small left pleural effusion. A head CT was notable for mild generalized cerebral and cerebellar volume loss with a few scattered hypodense foci within the central pons. A CT of the abdomen and pelvis, with oral and intravenous contrast, demonstrated free intraperitoneal air over the upper abdomen with periportal, retroperitoneal and mesenteric lymphadenopathy as well as pleural effusion with bibasilar atelectasis, left greater than right. The patient underwent urgent exploratory laparotomy for suspected small bowel perforation.
Case 1 - Slide 1
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Case 1 - Figure 1
Shows a low power view of the inflammatory infiltrate within the mucosa and lamina propria of the small intestine specimen (H&E).
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Case 1 - Figure 2
Is a low power view adjacent to that shown in Figure 1 revealing transmural inflammation (H&E). Adjacent to this area was a prominent ulcer which extended from the mucosa to the serosal surface.
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Case 1 - Figure 3
Shows diffuse granulomatous inflammation in the submucosa (H&E).
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Case 1 - Figure 7
Higher magnification reveals clusters of small yeasts within macrophages. Note the retraction of the fungus cytoplasm from the cell wall ("halo") giving the false impression of a capsule (H&E x1000). The halo effect is not seen using Gomori methenamine silver (GMS) stain as demonstrated in Figures 8 and 9..
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Case 1 - Figure 8
GMS stain (x500) revealing myriads and aggregates of dark stained intracellular and extracellular budding yeasts.
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Case 1 - Figure 9
GMS stain (x1000) high power view revealing details of small yeasts, 2-to-4 µm in diameter, having single buds with narrow necks.
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for Text and References
Submitted by: Jan M. Orenstein - George Washington University Medical Center, Washington, DC
This 4 month old infant was well until one month prior to death, when he developed fever, conjunctival injection, red dry cracked lips, rash and irritability. Lab tests showed a leukocytosis with WBC greater than 30,000, anemia, thrombocytopenia, and markedly elevated CRP. He was initially treated with antibiotics, and then intravenous gammaglobulin (IVIG) and aspirin therapy were administered. An echocardiogram initially showed mild ectasia of the coronary arteries. The patient continued to have fever after IVIG therapy, so additional antibiotics and another dose of IVIG was given. Repeat echocardiogram 5 days later showed diffuse coronary artery dilatation. Fevers persisted and he was treated with pulse doses of steroids and 2 doses of Remicaid. The baby then developed ST segment elevation on EKG and elevated troponin levels. He was placed on a heparin infusion, and EKG changes improved, but further testing (MRI and MRA) showed that he had developed extensive aneurysms of the coronary, brachial, axillary, and iliac arteries. The patient was stable, acting appropriately, and eating well until the morning of his death, when he developed respiratory and cardiac arrest. Stat CT angiography following stabilization showed a ruptured right iliac artery aneurysm. He was emergently taken to the operating room and his right iliac artery was ligated. However, he continued to require blood transfusions and inotropic support for refractory shock and DIC. He again suffered cardiac arrest and could not be resuscitated.
Images provided include the gross appearance of the heart and an H&E-stained section of lung.
Case 2 - Figure 1
Light microscopic studies of tissues from a patient with Kawasaki Disease. H&E of ciliated bronchial epithelium, demonstrating amphophilic supranuclear RNA-containing cytoplasmic inclusion bodies (arrows).
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Case 2 - Figure 2
Gross heart specimen from a patient with Kawasaki Disease demonstrating coronary artery aneurysms.
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for Text and References
Submitted by: J. Stephen Dumler - The Johns Hopkins University School of Medicine, Baltimore, MD
An 80 year-old white man from northwestern Wisconsin developed a fever and was admitted to the hospital 4 days later with additional complaints of confusion and cough. He had been in good health until this incident. After treatment with a third-generation cephalosporin without clinical benefit, he was transferred to a tertiary care facility where he complained of muscle pain and hyperventilating. Aside from his recent antibiotic, he took no medicines and had no allergies, had oral surgery one month before, had a remote history of a tick bite, and had not recently traveled. On physical examination, his temperature was 39.7°C, pulse 100 beats/min, blood pressure was 140/80 mmHg, and respiratory rate was 34/min. He was tachypneic and coughing thick mucus, but the physical examination revealed only significant proximal leg muscle pain, delirium, and heme-positive stools, without other respiratory, cardiovascular, or neurological signs. Laboratory studies revealed hyponatremia (127 meq/L), WBC 14.3/µL, platelets 15,000/µL, hemoglobin 15.4 g/dL, blood urea nitrogen 56 mg/dL, and creatinine 4.2 mg/dL; arterial blood gasses revealed pH 7.48, pCO2 25 mmHg, bicarbonate 18 mmol/L, pO2 53 mmHg with 89.9% saturation. LDH was 1855 IU/L, AST 491 IU/L, and total bilirubin 3 mg/dL. Chest X-ray and EKG examinations were unremarkable. The patient was treated for apparent sepsis with ceftriaxone, gentamicin, and metronidazole. Sputum gram stain, culture and cytology were unrevealing; blood cultures were sterile. Urine output dropped and did not respond to either fluid or diuretic challenges, and he was transferred to the ICU. Profound thrombocytopenia continued and PT and aPTT were 14.4 and 43 seconds. A peripheral blood smear evaluation revealed possible intracellular cocci within leukocytes, supporting a diagnosis of sepsis. One day after admission, hypoxia continued and he had several episodes of hematemesis; fibrin split products were elevated, but his fibrinogen level was 438 mg/dL, the WBC dropped to 10.6/µL, and PT and aPTT climbed to 16.5 and 57 sec. He was treated with platelet transfusions and fresh frozen plasma, and antimicrobial coverage was expanded by adding clindamycin. BUN, creatinine, bilirubin, and AST levels continued to climb, and hemoglobin dropped to 6.9 g/dL, and he developed multiorgan failure and ARDS.
Case 3 - Slide 1
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Case 3 - Figure 1
Anaplasma phagocytophilum "morulae" or clusters within a band neutrophil of the patient with human granulocytic anaplasmosis. Note the basophilic staining and stippled appearance of the cluster that conforms to the size and shape of an intracytoplasmic vacuole. Wright stain, original magnification 1,000X
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Case 3 - Figure 2
Gastroesophageal junction ulcer with hemorrhage in the patient with human granulocytic anaplasmosis. H&E, original magnification 25X
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Case 3 - Figure 3
Gastroesophageal ulcer demonstrating budding yeast with pseudohyphae, most consistent with Candida albicans esophagitis. Giemsa stain, original magnification 1,000X
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Case 3 - Figure 4
Lung demonstrating intra-alveolar hemorrhage and mild interstitial lymphohistiocytic infiltrate and alveolar wall edema. H&E, original magnification 400X
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Case 3 - Figure 5
Liver demonstrating the mild lobular and periportal infiltrates composed predominantly of lymphocytes and histiocytes and Kupffer cell hyperplasia. H&E, original magnification 40X
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Case 3 - Figure 6
Liver demonstrating focal hepatocyte apoptosis among a mild lymphohistiocytic lobular infiltrate and Kupffer cell hyperplasia. H&E, original magnification 200X
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Case 3 - Figure 7
Spleen from patient with human granulocytic anaplasmosis that demonstrates lymphoid cell depletion with a relative increase in mononuclear phagocyte populations, many of which appear activate or are actively hemophagocytic. H&E, original magnification 400X
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Case 3 - Figure 8
Spleen from the patient with human granulocytic anaplasmosis demonstrating intracytoplasmic inclusions or morulae within neutrophils. Giemsa, original magnification 1000X
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Case 3 - Figure 9
Splenic neutrophil with intracytoplasmic morula. Note the membrane-bound inclusion that contains several pleomorphic bacteria that range in shape from coccoid to coccobacillary. The preparation was from formalin-fixed tissue previously embedded in paraffin and retrieved for transmission electron microscopy. Original magnification 15,000X
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Case 3 - Figure 10
Spleen demonstrating the presence of A. phagocytophilum (red color) within neutrophils in sinusoids. Immunohistochemistry using rabbit-anti-A. phagocytophilum.
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Case 3 - Figure 11
Immunohistochemical demonstration of A. phagocytophilum within neutrophils infiltrating the esophageal ulcer (left panel) and lung (right panel). Immunohistochemistry using rabbit-anti-A. phagocytophilum.
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Case 3 - Figure 12
A. phagocytophilum cultivated from the blood of a patient with human granulocytic anaplasmosis using the HL-60 promyelocytic cell line. The left panel demonstrates the typical morulae that appear within the cytoplasm of the infected HL-60 cell (LeukoStat stain; original magnification 1,000X). The right panel demonstrates the ultrastructural appearance of the morulae and bacterial contents in transmission electron microscopy (original magnification; 12,000X).
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for Text and References
Submitted by: Sherif R. Zaki - Centers for Disease Control, Atlanta, GA
In February 2003, a previously healthy 25 year old male visited his physician with head and body aches, nausea, abdominal pain, chills, fever of 99°-100°F, dry cough, and listlessness. Upon retrospective questioning, his wife reported that he had showed mild personality changes during the previous days. Six days later, the patient awoke disoriented with unsteady gait and slurred speech. He was evaluated in a local emergency department and admitted to the hospital. Physical examination revealed mild ataxia and confusion. Laboratory values were substantial for decreased sodium. A lumbar puncture revealed a white blood cell count of 24/µL, a red blood cell count of 10/µL, a glucose concentration of 58 mg/dL, and a protein concentration of 81 mg/dL. An electroencephalogram demonstrated generalized slowing. Magnetic resonance imaging of the brain was interpreted with a high T2 signal in the hypothalamus and bilateral mesial temporal lobes. The patient remained febrile and hyponatremic (range: 119--125 mmol/L) with declining mental status. On the fifth day of hospitalization, the patient was intubated, and twitching on his right side was noted. On day six, he was unresponsive and had near-constant myoclonic activity. On the 11th day, a computerized tomography scan of the head showed sulcal effacement and diffuse cerebral edema. The patient remained comatose and intermittently febrile. Despite aggressive critical care management, the patient died on the 14th hospital day. At autopsy, histopathologic evaluation showed severe meningoencephalitis involving the cortex and white matter of the cerebral hemispheres, deep gray nuclei, cerebellum, and spinal cord. Brain tissue submitted to a research laboratory was positive by polymerase chain reaction (PCR) for Naegleria.
Case 4 - Slide 1
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