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Infectious Disease Pathology
Monday, March 3, 2008, 7:30 PM
Convention Center 108/110/112 Zoonotic Bacterial Infections
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Moderator:
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STEPHEN DUMLER
Johns Hopkins University School of Medicine
Baltimore, MD
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Disclosure:
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The speakers have indicated they have nothing to disclose.
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Clinical histories are displayed below.
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for Text and References
Submitted by: Wun-Ju Shieh - Infectious Diseases Pathology Activity, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA
A 38-year-old female working in a media company in New York City noticed a painless small papule on her left clavicle that was not erythematous nor pruritic. Three days later, the lesion became erythematous, with surrounding edema and measured approximately 1 cm in diameter. The following day, she took an oral antibiotic that remained from a previous prescription because of mild headache and malaise, and also applied topical Bacitracin on the skin lesion. After two days of self-treatment with no apparent improvement, the patient visited a local infectious disease physician. The skin lesion was 5 cm in diameter, with a raised border and central depression. It was associated with significant edema obscuring her clavicle and intense erythema involving the upper left chest and shoulder. Several small satellite vesicles surrounded the lesion and left cervical lymphadenopathy were noted on physical examination. A small amount of serous fluid from the wound was sent for Gram stain and culture, which yielded no growth. The initial diagnosis was an arthropod bite with secondary infection and ciprofloxacin was prescribed. She returned to the clinic two days later with no significant gross change of the lesion. A complete blood count and serum electrolyte obtained at that time were within normal limit. After one week of continuous antibiotic treatment, the lesion had improved significantly. However, after seeing pictures of similar lesion on the internet, the patient visited another infectious disease physician for second opinion. A skin biopsy was taken for histopathologic evaluation and subsequent diagnostic workup. She was continued on ciprofloxicin for another week with complete resolution of the lesion.
Case 1 - Slide 1
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Case 1 - Figure 1
Skin biopsy from the edge of the eschar shows intact epidermis. Superficial ulceration and fibrinopurulent membrane typically associated with acute lesion of cutaneous anthrax were not seen. H & E stain, original magnification x 12.5.
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Case 1 - Figure 2
The adjacent dermis shows edema, focal hemorrhage, and perivascular mononuclear cell infiltrates. H & E stain, original magnifications x 12.5
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Case 1 - Figure 3
A higher magnification of the dermis illustrates the edema and intense perivascular mononuclear inflammatory cell infiltrates. H & E stain, original magnifications x 50.
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Case 1 - Figure 4
This higher magnification further demonstrates the polymorphous nature of the perivascular inflammatory cell infiltrate dominated by mononuclear phagocytes and lymphocytes with focal hemorrhage. H & E stain, original magnification x 158.
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for Text and References
Submitted by: Margie Scott
This 56 year old healthy active Arkansas outdoorsman had noted a firm, non-tender persistent 'lump' of the left neck measuring 3x4cm for a period of greater than 6 months. This was first brought to the attention of his primary care provider last November at which time he reported a brief period of fevers and sweats that began about the time he noted the lump. He was treated empirically with a broad spectrum antibiotic and noted resolution of the fevers and sweats, but persistence of the neck mass. Despite two additional courses of empiric antibiotics, the mass remained becoming somewhat softer to the touch. CBC, basic metabolic chemistry panel and Urinalysis testing were all within normal limits. Chest X-ray was normal. No cultures were obtained. A series of serologic studies focusing on tick-born diseases were obtained (RMSF, Ehrlichia, tularemia, Bartonella, Borrelia) and the patient was scheduled for elective lymph node excision the following May. The H&E slide and four images provided are from the excised lymph node.
Please note: During the operative procedure the surgeon placed a phone call to determine how to best handle the specimen.
Case 2 - Slide 1
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Case 2 - Figure 1
Low power view of infected lymph node showing necrosis, foci of surrounding histiocytes and scattered granulomas at margin of lesion (H&E, 10x)
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Case 2 - Figure 2
High power view of lymph node giant cells demonstrating amber colored polarizable foreign material within cytoplasm (H&E, 40x)
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Case 2 - Figure 3
Discrete zonal necrosis with surrounding palisading histiocytes and adjacent giant cells mixed within nodal lymphocytes. (H&E, 10x).
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Case 2 - Figure 4
High power of interface between confluent zonal necrosis and histiocytic rim. (H&E, 40x).
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for Text and References
Submitted by: Benjamin M. Greenberg - The Johns Hopkins University School of Medicine, Baltimore, MD
A 65-year-old Iranian immigrant man living in the United States was in his usual state of good health until a return visit to Iran 15 months prior to his diagnosis. In Iran, he developed right upper quadrant pain accompanied by a fever. An abdominal ultrasound examination revealed gallstones, and a cholecystectomy was performed. His postoperative course was uncomplicated, but 2 months later he developed right flank pain and bilateral knee pain. He then developed bitemporal headaches without constitutional symptoms, followed by otalgia and subtotal hearing loss on the right. Within weeks, there was progression and extension of hearing loss to the left. His symptoms persisted despite antibiotic treatment for presumed ear infection. He developed horizontal diplopia along with anorexia, nausea, and vomiting in association with his headaches. Evaluation of a cerebrospinal fluid sample was ''normal,'' although no results were available for review. The patient experienced a gradual, slowly progressive neurocognitive decline characterized by mild confusion, dysarthria, low mood, anhedonia, insomnia, and sexual dysfunction.
By the time he returned to the United States 9 months after his initial presentation, the patient had suffered a 13.6-kg weight loss and had persistent gastrointestinal and neurologic signs. An audiogram confirmed bilateral sensorineural hearing loss. There were mild cognitive impairments in verbal fluency, sequencing, and copying of written figures. Other neurologic functions were normal. A magnetic resonance image of the brain revealed diffuse, bilateral white matter T2 hyperintensities without parenchymal enhancement. Cerebrospinal fluid studies revealed a mild pleocytosis (white blood cells, 13/mm3, predominantly mononuclear cells) with normal protein (35 mg/dL) and glucose (54 mg/dL) concentrations. There were 2 oligoclonal bands, and the immunoglobulin (Ig) G index was 0.7 (normal range, up to 0.9). Serologic studies for human immunodeficiency virus, syphilis, neuroborreliosis, Ehrlichiosis, and Whipple disease's PCR were negative, as were routine blood and cerebrospinal fluid cultures. Serologic studies for known autoimmune and rheumatologic disorders were negative. Serologic studies for hepatitis C, A, and B surface antigens were negative, but there was evidence of anti-hepatitis B surface antibodies. Because of the magnetic resonance image evidence of a diffuse and symmetric white matter involvement, including prominent involvement of the subcortical u-fibers, and lack of enhancement, a panel of studies directed at late-onset leukodystrophies was obtained, again without diagnostic benefit. Despite clinical improvement in cognitive deficits with antidepressant treatment, the magnitude of white matter lesions led to a decision to obtain a brain biopsy. Perioperative magnetic resonance images revealed an evolving, leptomeningeal enhancing lesion in the left Sylvian fissure.
Case 3 - Slide 1
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Case 3 - Figure 1
Right frontal cortex and white matter biopsy reveal meningoencephalitis characterized by a lymphocytic infiltrate in the leptomeninges and surrounding cortical vessels (H&E).
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Case 3 - Figure 2
Right frontal cortex and white matter biopsy reveal meningoencephalitis characterized by a lymphocytic infiltrate in the leptomeninges and surrounding cortical vessels (H&E).
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Case 3 - Figure 3
Inflammatory cells were especially abundant in the white matter around vessels and infiltrating through the parenchyma (H&E).
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Case 3 - Figure 4
Inflammatory cells were especially abundant in the white matter around vessels and infiltrating through the parenchyma (H&E).
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Case 3 - Figure 5
Marked reactive astrogliosis is demonstrated throughout the cortex and white matter (H&E).
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Case 3 - Figure 6
Marked reactive astrogliosis is demonstrated throughout the cortex and white matter (H&E).
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Case 3 - Figure 7
Immunostaining of major histocompatibility complex class II antigens (human leukocyte antigen DR marker) demonstrates the marked activation of microglia.
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Case 3 - Figure 8
Immunophenotyping of the T cell infiltrates in the white matter and cortex revealed that the majority of the CD4 and CD8 T cells were CD81 lymphocytes.
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Case 3 - Figure 9
No significant myelin destruction was shown in Luxol fast blue stains.
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for Text and References
Submitted by: Rebecca A. Irvine - University of New Mexico, Albuquerque, NM
A 54-year-old Caucasian, non-Hispanic woman from the East Mountains, near Albuquerque, New Mexico, was transferred to an Emergency Department from an Urgent Care Center. She had initially presented with a 5-day history of back and abdominal pain, sinus-headache type pain, "flu"-like symptoms and, most recently, bloody stool and emesis. At the Urgent Care center it had been noted that she was anuric with a WBC of 52K. She arrived at the E.D. unresponsive with agonal respirations and was promptly intubated. Despite continuous efforts at resuscitation, she was pronounced dead less than two hours after admission. There was no record of administration of broad-spectrum antimicrobials or obtaining a chest radiograph.
An automated complete blood count could not be obtained. Manual reading showed a WBC of 31.7K, 67% PNMs and a platelet count of 45K. There was a pronounced left shift and toxic granulation was noted. Additionally, many bacteria were identified in antemortem blood specimens. Liver function testes were elevated and BUN & creatinine were 35 and 1.7 mg/dL, respectively. Lactic acid was greater than 12.0 mg/dL and quantitative D-DIMER was greater than 20.00.
Her past medical history included a breast lumpectomy, lumbar spine surgery, appendectomy, tobacco use, past ethanolism (none for three years) and an allergy to penicillin. She had previously been in her usual state of health. There was no foreign travel, no transfusion history and family members were unaware of any contact with vectors.
A complete autopsy was performed under the jurisdiction of the Medical Examiner approximately 11 hours after death. The decedent appeared acutely ill, without any identifiable external injuries. Grossly there was marked pulmonary congestion with a combined lung weight of 2,150 grams. The lungs were without focal or regional consolidation and while "wet", they were not "beefy" or airless. Frank blood was present throughout the upper gastrointestinal tract, without a focal source. There was no lymphadenopathy or recurrent mammary carcinoma.
Case 4 - Slide 1
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Case 4 - Figure 1
Lung alveolar spaces with fibrin microthrombi and focal intra-alveolar bacteria overgrowing the septa.
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Case 4 - Figure 2
Occlusive fibrin thrombus in a pulmonary venule within which bacteria can be easily identified.
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Case 4 - Figure 3
Abundant intravascular bacteria are noted on multiple sections.
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Case 4 - Figure 4
Kidney with fibrin thrombi in capillary loops, overgrown with bacteria.
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for Text and References
Submitted by: Christopher D. Paddock - Centers for Disease Control and Prevention, Atlanta, GA
A 78 year-old woman-from northern Maryland presented to her physician in August 2006 following several days of fever, headache, myalgia, nausea, vomiting, and a generalized maculopapular rash. Physical examination revealed a temperature of 99.7° F and >50 small (5 to 6 mm), nonpruritic maculopapules involving her trunk and extremities, including her palms. A 1 × 1 cm, nontender, nonpruritic, ulcerated lesion with central necrosis was also identified on her right upper back. There was no adenopathy. Her serum alanine aminotranferase (ALT) and aspartate aminotransferase (AST) levels were mildly elevated at 38 U/L and 41 U/L, respectively. Her white blood cell and platelet counts were within normal limits. During the weeks preceding her illness, the patient had not traveled out of the United States, and she did not recall a specific arthropod bite or exposure.
The patient was admitted to a hospital with diagnosis of Rocky Mountain spotted fever and started on intravenous doxycycline, with rapid resolution of her fever. A 4 mm punch biopsy of the necrotic lesion on her back was obtained. The specimen was bisected with one portion submitted for routine histopathology, and the other submitted to the Centers for Disease Control and Prevention for further diagnostic evaluation.
Case 5 - Slide 1
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Case 5 - Figure 1
Skin punch biopsy specimen with extensive, superficial and deep, perivascular inflammatory infiltrates and focal necrosis and ulceration of the epidermis (H&E).
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Case 5 - Figure 2
Necrosis of the superficial dermis and partially occlusive fibrin thrombi in small vessels of the subjacent tissue (H&E).
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Case 5 - Figure 3
Perivascular inflammatory cell infiltrate comprised predominantly of lymphocytes and macrophages; involved vessels exhibit prominent swelling of endothelial cells (H&E).
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Case 5 - Figure 4
Infiltrates extending into the panniculus and eccrine ducts (H&E).
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Case 5 - Figure 5
Immunohistochemical stain for spotted fever group rickettsiae identifying scattered collections of intracellular coccobacilli within the inflammatory infiltrates.
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