and Pallav Gupta2
(1)
Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
(2)
Department of Histopathology, Sir Ganga Ram Hospital, New Delhi, India
Viral infections most often represent reactivation of latent or subclinical infection in immunocompromised host. Both viral and host factors determine the susceptibility to infection. The susceptibility and severity of viral infections increases in conditions with inherited or acquired immunodeficiency, immunosuppressive drug therapy, or transplant recipients or in patients with compromised cellular immunity, e.g., AIDS.
The laboratory techniques utilized for the diagnosis of viral infections include direct visualization (cytology, histology, and electron microscopy), viral culture, detection of viral antigens (radioimmunoassay, enzyme immunoassay, and immunofluorescence), and serological detection of antibodies. Currently molecular techniques based on the detection of viral genome are being increasingly used for the diagnosis of viral infections.
Commonly encountered opportunistic viral pathogens are listed in Table 3.1.
Table 3.1
Common opportunistic viral pathogens
Family | Subfamily | Example |
|---|---|---|
DNA viruses | ||
ds DNA viruses | ||
Herpesviridae | Alphaherpesvirinae | |
Simplex virus | Human herpes virus 1 and 2 (HSV) | |
Varicella virus | Human herpes virus 3 (varicella-zoster) | |
Betaherpesvirinae | ||
Cytomegalovirus | Human herpes virus 5 (CMV) | |
Roseolovirus | Human herpes virus 6 and 7 | |
Gammaherpesvirinae | ||
Lymphocryptovirus | Human herpes virus 4 (EBV) | |
Rhadinovirus | Human herpes virus 8 (KSHV) | |
Polyomaviridae | Polyomavirus | JC, BK virus |
Papillomaviridae | Papillomavirus | Human papillomavirus (HPV) |
Ss DNA viruses | Parvovirinae | |
Parvoviridae | Erythrovirus | B19 |
Herpes Simplex Virus (HSV):
Herpes simplex virus (HSV) includes two serotypes HSV 1 and HSV 2. HSV can involve any organ or mucocutaneous site. However, HSV 1 is usually said to affect upper half of the body causing oral lesions and HSV 2 the lower half, involving genital organs. Neonatal herpes simplex is caused by HSV 2 in 70 % and by HSV 1 in 30 % cases. The infection is acquired during vaginal delivery and can be prevented by cesarean section.
Immunocompromised patients show extensive lesions and frequently develop disseminated disease involving the esophagus, upper respiratory tract, lung, and liver. Other organs like the adrenals, pancreas, intestine, and bone marrow may also be involved.
Microscopic examination reveals that the epithelial cells lining the vesicular cutaneous and mucosal lesions show eosinophilic homogenous cytoplasm and nucleomegaly with viral inclusions. The inclusions are 3–8 μm, round to oval, amphophilic, and homogenous with ground glass appearance surrounded by a halo, and multinucleation may also be present.
Tzanck smear can be prepared for rapid preliminary diagnosis. Cytological specimen like vesicular fluid and scrapings from the base of the lesions stained with Giemsa, Papanicolaou, or toluidine blue may show characteristic giant cells and acantholytic balloon cells with intranuclear inclusions of herpes. In herpes pneumonia, bronchial biopsy and brushings may show characteristic viral inclusions in alveolar lining cells. Immunohistochemistry and fluorescent techniques with specific antibodies can be applied on paraffin-embedded tissue.
Herpetic Esophagitis in an Immunocompromised Patient
Fig. 3.1
(a–c) A 43-year-old female patient a known case of ulcerative colitis on long-term steroids, presented with dysphagia; there was no significant weight loss. Upper GI endoscopy showed multiple ulcers in lower esophagus. Laboratory workup revealed hemoglobin of 10.1 g/dl, TLC 9800/cu mm with neutrophils 61, lymphocytes 30, eosinophils 2, and monocytes 7 %, respectively. The platelet count was 233,000/cu mm. Histopathological examination of the endoscopic esophageal biopsy from ulcerated area revealed herpetic esophagitis (a HE ×200, b, c HE ×400)
Cytomegalovirus (CMV):
CMV is an opportunistic pathogen and may produce persistent lifelong infection. It can be transmitted both vertically and horizontally through blood transfusion, sexual contact, and transplanted organs and from mother to the neonate by placenta, by cervicovaginal canal during child birth, or even through breast milk. Fetal transmission is seen in 20–30 % CMV-infected pregnant women.
In immunocompromised patients the severity of CMV disease correlates with the degree of immunosuppression. CMV-infected patients are known to develop superinfection with other pathogens like bacteria and fungi.
Tissue biopsy from the involved organ shows cytomegaly and nucleomegaly with the presence of characteristic intranuclear inclusions (Cowdry type A) in epithelial and/or endothelial cells. These inclusions are single, homogenous, and round to oval with smooth outline and appear amphophilic to basophilic in HE-stained sections. Intracytoplasmic inclusions may also be present. They are small, multiple, irregular, granular, and basophilic and are usually present in perinuclear zone; they are PAS and GSM positive. Immunohistochemistry performed on paraffin sections enhances the sensitivity of histological diagnosis.
Immunocompromised patients are unable to mount prompt immune response; hence, serodiagnosis may be inconclusive. PCR has replaced the cell culture as “gold standard” for CMV detection.
CMV Esophagitis in a Renal Allograft Recipient
Fig. 3.2
(a, b) A-48-year-old male patient receiving live-related renal allograft presented 3 months posttransplant with complaints of epigastric discomfort. Upper GI endoscopy revealed mucosal hyperemia of the esophagus with the presence of edema and multiple linear ulcers. Biopsy from the ulcer showed inflammatory infiltrate; endothelial cells lining the capillaries showed marked cytomegaly and nucleomegaly and prominent eosinophilic intranuclear inclusions (arrows) suggestive of CMV esophagitis (a HE ×200, b HE ×400)
CMV Duodenitis in a Renal Allograft Recipient
Fig. 3.3
(a–d) A-53-year-old male patient who received live-related renal allograft 10 years ago, presented with nausea and vomiting for 20 days. At admission to the hospital, his hemoglobin was 10.4 g/dl, and the serum creatinine was 3.31 mg/dl. TAC level was high; therefore, tacrolimus dose was reduced. Upper GI endoscopy revealed duodenal erosion. Duodenal biopsy showed that some of the glandular epithelial cells had nucleomegaly with intranuclear inclusions giving an owl eye appearance (arrows) suggestive of CMV duodenitis (a–d HE ×400)
CMV Gastritis in a HIV-Positive Patient
Fig. 3.4
A 56-year-old female patient with history of blood transfusion from a professional donor for ovarian surgery 8 years back presented with increased frequency of stools, large volume of watery diarrhea, occasional vomiting, loss of weight, and fever. Upper GI endoscopy revealed nodularity in the upper esophagus and stomach. Gastric biopsy showed mucosal ulceration along with cytomegaly and nucleomegaly with the presence of intranuclear “owl eye” inclusions in the glandular epithelial and endothelial cells (arrows), diagnostic of CMV gastritis (HE ×400). On subsequent investigations, the patient was found to be HIV positive with absolute CD4 count of 138/cu mm
CMV Colitis in Renal Allograft Recipient
Fig. 3.5
(a, b) A 40-year-old male patient who received live renal allograft 7 years back and was maintained on triple drug immunosuppression, presented with persistent loose motions, weakness, and loss of weight for 3 months. His hemoglobin at admission was 9.1 g/dl; other lab parameters were within normal limits. Upper GI endoscopy did not reveal any abnormality; however, lower GI endoscopy showed multiple ulcers throughout the colon and sigmoid; multiple punch biopsies were obtained. The histological examination showed that some of the glandular epithelial cells had nucleomegaly with intranuclear inclusions giving an owl eye appearance (arrows) suggestive of invasive CMV colitis (a, b HE ×400). CMV PCR was positive
CMV Lung Disease in a HIV-Positive Patient
Fig. 3.6
(a, b) A 6-year-old male child presented with breathlessness for 4 months with fever and loss of weight for 1 month. The patient was HIV positive and was on retroviral therapy. Both parents were also HIV positive. CT chest revealed large cavity in the upper lobe of right lung with mass effect on the lower lobe with diffuse lung disease (a). Lobectomy of the upper lobe of right lung was performed. Histological examination of the resected lobe of the lung revealed that at places lining alveolar cells showed cytomegaly and nucleomegaly along with intranuclear owl eyelike inclusions suggestive of CMV lung disease (b HE ×1000) (Contributors – S. Radha and Tameem Afroz, Aware Global Hospital, Hyderabad, India)
CMV Skin Disease in a Renal Allograft Recipient
CMV Disease in Fetus
Fig. 3.7
(a–c) A 55-year-old male patient receiving spousal renal allograft was being maintained on triple drug immunosuppression. He developed posttransplant diabetes mellitus for which he received insulin. Three months later, he presented with multiple vesicular eruptions over the right axilla, scrotum, and penile skin for 6 weeks followed by fever for 2 weeks. His serum creatinine was 2.51 mg/dl, and he was anemic with a hemoglobin level of 5.6 g/dl. The patient had polymorphonuclear leukocytosis, total WBC count being 24,500/cu mm with 83 % neutrophils. Skin biopsy from the axillary ulcers revealed massive nucleomegaly with intranuclear owl eyelike inclusions (arrows) diagnostic of CMV disease in several vascular endothelial cells (a–c HE ×400)
Fig. 3.8
(a–c) A 21-year-old primigravida delivered a stillborn fetus at 30 weeks of gestation. Fetal autopsy revealed massive hepatosplenomegaly with ascites. Provisional diagnosis of inborn errors of metabolism with hydrops fetalis was considered. Histopathological examination of both the kidneys showed fair number of tubular epithelial cells bearing intranuclear owl eyelike inclusions (a HE ×400). Immunohistochemistry with anti-CMV antibody showed positive staining in the cells showing nuclear inclusions. Sections from the liver and lungs also showed similar intranuclear inclusions in ductal and alveolar epithelial cells (b, c HE ×400). HIV status of fetus or parents was not known (Contributor – Prof. Vinita Agrawal, Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India)
