AIDS and GIT Slides PDF, August 2024

AIDS AND THE GIT Dr LR Sewpaul Department of Anatomical Pathology Date: August 2024 INTRODUCTION AIDS – Acquired immunodeficiency syndrome Profound immune suppression Characterised by profound immunosuppression that leads to: Opportunistic infections S...

AIDS AND THE GIT Dr LR Sewpaul Department of Anatomical Pathology Date: August 2024 INTRODUCTION AIDS – Acquired immunodeficiency syndrome Profound immune suppression Characterised by profound immunosuppression that leads to: Opportunistic infections Secondary neoplasms Neurological manifestations INTRODUCTION The two major targets of HIV are the central nervous system and the immune system Gastrointestinal tract (GIT) houses most of the body’s lymphocytes, including activated memory CD4+ T cells that are preferential targets for HIV irrespective of mode transmission. INTRODUCTION Aim: Review the pathologic findings of neoplastic, noninfectious and infectious HIV-associated gastrointestinal disorders: Oral cavity Oesophagus Stomach Large and small bowel Anus and perianal area INTRODUCTION INFECTIONS: OTHER: Recurrent aphthous ulcers Candidiasis Hairy leukoplakia Herpes simplex infection(HSV) Cytomegalovirus infection(CMV) Human Papilloma Virus infection(HPV) Periodontal diseases MALIGNANCIES: Kaposi Sarcoma Lymphoma INFECTIONS - CANDIDIASIS Commonest infection of the esophagus but may infect any level of the GI tract. Risk factors: Immunosuppression Chemotherapy & corticosteroids Major abdominal surgery. Candida albicans is most commonly isolated. INFECTIONS - CANDIDIASIS Pathology White plaques that easily scrape away Ulcerated underlying mucosa Ulceration, pseudomembrane formation and inflammatory masses Ulcers are often multiple, irregular, and hemorrhagic, and may be confluent in advanced cases. INFECTIONS - CANDIDIASIS Granulomas (occasionally) Intra-epithelial neutrophils Different morphologies: Yeast-like = blastoconodia Pseudohyphae = budding yeast cells joined end to end True hyphae with septae INFECTIONS – CRYPTOCOCCUS This fungus is a rare but important cause of gastrointestinal infection. Two species cause disease in humans Cryptococcus neoformans Cryptococcus gatti Within the GIT, the colon is the most frequently involved site, followed by the esophagus Virtually all patients with gastrointestinal cryptococcosis have disseminated disease with multisystem organ involvement, and most have associated pulmonary and meningeal disease. INFECTIONS – CRYPTOCOCCUS Endoscopic lesions: Nodules and ulcers, sometimes associated with thick white exudates. Mucosa is normal in many cases. Inflammatory reactions depends on the immune status Suppurative, necrotizing inflammatory reaction Often with granulomatous features No reaction in anergic hosts. INFECTIONS – CRYPTOCOCCUS Both superficial and deep involvement may occur, and lymphatic involvement is common Fungal cells are surrounded by optically clear, smooth “halos” that represent the unstained or weakly stained capsules, and impart a “soap-bubble” appearance INFECTIONS - HISTOPLASMOSIS Histoplasma capsulatum var. capsulatum is endemic to the central United States, especially within the Ohio, Missouri, and Mississippi river valleys. It is most plentiful in soil enriched by avian or bat droppings. Disseminates through the mononuclear phagocyte system and gastrointestinal involvement occurs in more than 80% of patients with disseminated infection. INFECTIONS - HISTOPLASMOSIS It is the most common endemic mycosis in patients with AIDS. Histoplasmosis has also been described in association with infliximab therapy. Gastrointestinal symptoms include diarrhea, gastrointestinal bleeding, abdominal pain, dysphagia, nausea, vomiting, weight loss, and signs of small bowel obstruction. Gastrointestinal bleeding and anorectal disease are more common in patients with AIDS. INFECTIONS - HISTOPLASMOSIS The ileum is the most common site of involvement, followed by colon, stomach, and esophagus; any portion of the gastrointestinal tract may be involved. Associated lymphadenopathy is common. Ulcers are the most common gross lesion; they are often multiple, with annular raised borders, associated hemorrhage, and necrosis at the base. INFECTIONS - HISTOPLASMOSIS Nodules (often centered on lymphoid aggregates) and obstructive masses or strictures are also common Diffuse lymphohistiocytic infiltrates and nodules usually involving the mucosa and submucosa, with associated overlying ulceration. Non- specific ulceration and inflammation with numerous organisms present in the bowel wall also may be seen. INFECTIONS - HISTOPLASMOSIS Abdominal lymph nodes often show necrotizing granulomas Histoplasma organisms are small (2–5 μm), ovoid, usually intracellular yeast forms with single small buds at the more pointed pole = narrow- neck budding Organisms stain with PAS and Grocott stains. INFECTIONS - PNEUMOCYTOSIS Causative organism is pneumocystis jeroveci Extrapulmonary infection has been discovered in 2.5% of patients with AIDS at autopsy GI pneumocystosis develops after blood and lymphatic dissemination from the lung or from reactivation of latent GI infection that seeded previously Usually occurs when CD4 count < 50 INFECTIONS - PNEUMOCYTOSIS Sites of infection: oesophagus, stomach, duodenum and colon Non-specific, often erosive, esophago-gastritis or colitis, occasionally with small polypoid nodules Microscopy Granular, foamy eosinophilic casts identical to those seen in pulmonary disease, and often referred to as “honeycomb exudates,” may be seen within mucosal vessels or within the lamina propria. INFECTIONS - PNEUMOCYTOSIS The organisms are 5–7 μm spherules that have cup or crescent shapes when collapsed. Many contain characteristic single or paired comma-shaped internal structures. Organisms stain with GMS and toluidine blue. INFECTIONS - CMV Most common GIT pathogen overall in patients with AIDS Can develop anywhere in the GIT - from mouth to anus. Symptoms vary acc.: immune status and the site of infection Most common symptoms of GIT infection: diarrhea (either bloody or watery), abdominal pain, fever, and weight loss. Patients with esophageal infection often have dysphagia and odynophagia. INFECTIONS - CMV Ulceration: most common May be single / multiple Superficial / deep. May be very large (greater than 10.0 cm) Often have a well-circumscribed, “punched-out” appearance with intervening normal mucosa. Segmental ulcerative lesions and linear ulcers may mimic Crohn’s disease grossly INFECTIONS - CMV Crypt abscesses, crypt atrophy, and apoptotic enterocytes may be seen as well. Prominent aggregates of macrophages may be seen surrounding viral inclusions. Characteristic inclusions with virtually no associated inflammatory reaction may occur in severely immunocompromised patient INFECTIONS - CMV Infected cells show both nuclear and cytoplasmic enlargement. Characteristic “owl’s eye” intranuclear viral inclusions and basophilic granular intracytoplasmic inclusions. Inclusions are preferentially found in endothelial cells, stromal cells, and macrophages and rarely in glandular epithelial cells INFECTIONS – HERPES SIMPLEX VIRUS Herpes simplex virus (HSV 1 + 2) is a member of the herpesvirus group Also includes varicella zoster virus (HHV-3), Epstein–Barr virus (HHV- 4), Cytomegalovirus (HHV-5), and HHV types 6 + 7, and KSHV / HHV- 8 HSV infection may occur throughout the gastrointestinal tract most common in the esophagus and anorectum. INFECTIONS – HERPES SIMPLEX VIRUS HSV esophagitis: odynophagia, dysphagia, chest pain, nausea, vomiting, fever, and gastrointestinal bleeding. Ulcers are the most common gross finding in the esophagus, and these are usually associated with an exudate. The ulcers are often shallow and sharply demarcated, with surrounding relatively normal mucosa. Some patients have vesicles surrounding the ulcers. Many have non-specific erosive esophagitis. The diagnosis should be suspected in the presence of superficial punched-out ulcers (frequently covered with fibrinous material) at endoscopy INFECTIONS – HERPES SIMPLEX VIRUS Typical histologic findings, regard-less of site: Ulceration Inflammatory exudate that often contains sloughed epithelial cells Neutrophilic infiltrate in the lamina propria. Prominent aggregates of macrophages may be seen  Multinucleation Moulding Margination Nuclear inclusions Homogenous “ground glass” Or acidophilic inclusions with a surrounding clear halo INFECTIONS - HPV Human papillomaviruses (HPV) have been implicated in the pathogenesis of esophageal papilloma esophageal squamous cell carcinoma anal condyloma anal squamous intraepithelial lesions anal squamous cell carcinoma INFECTIONS - HPV Esophageal squamous papillomas(ESP) Most common benign epithelial tumor of the esophagus Usually asymptomatic, and found incidentally May cause epigastric pain, dysphagia, or signs of obstruction HPV – ESOPHOGEAL SQUAMOUS PAPILLOMA Endoscopically: discrete, sessile, or pedunculated white polyps with an exophytic or verrucoid appearance. HPV – ESOPHOGEAL SQUAMOUS PAPILLOMA Microscopically multilobulated lesions with fibrovascular cores that extend outward from the center of the papilloma Nuclei may be slightly enlarged with surrounding clear halos ANAL HPV INFECTION Condyloma acuminatum Most common tumor of the anal and perianal region Grossly Soft, fleshy, white to pink papillomatous lesions that can be single or multiple Large lesions may have a cauliflower-like appearance. ANAL HPV INFECTION Microscopically Papillary with acanthosis, surface maturation, and parakeratosis Koilocytic atypia is common (featuring enlarged, irregular, hyperchromatic nuclei with frequent binucleation and surrounding halos) HIV The two major entities associated with HIV in the absence of other demonstrable pathogens Chronic idiopathic esophageal ulcers AIDS enteropathy/colopathy Chronic HIV-associated esophageal ulcers Patients present with severe odynophagia, independent of food intake, chest pain, and weight loss. Massive, even fatal GI bleeding can occur if the ulcer erodes into vessels. Stricture formation rare. Pathological features The middle 1/3 of esophagus is the most common location, followed by the distal esophagus. Endoscopically: one or more well circumscribed lesions of variable depth. Can be large, greater than 3.0 cm with irregular margins and over-hanging, edematous edges. They are often linear. Mucosal bridges and sinus tract formation may occur. Pathological features Histologically, the ulcers contain granulation tissue with a mixed acute and chronic inflammatory infiltrate that often contains eosinophils. The ulcers may extend into the esophageal muscle layers. By definition, special histochemical stains and immunohistochemical stains for identifiable pathogens must be negative. AIDS (HIV) enteropathy/colopathy Loosely defined as the morphologic changes seen in the gut of patients with HIV/AIDS and chronic diarrhea, for which no other infectious cause has been identified. The controversy arises because asymptomatic patients may have similar morphologic findings on biopsy, and conversely severely symptomatic patients may have normal biopsies. Endoscopy and colonoscopy are usually normal. AIDS (HIV) enteropathy/colopathy Small bowel: microscopic features include villous blunting and atrophy, crypt hypertrophy, and increased intraepithelial lymphocytes. Variably increased mononuclear cells in the lamina propria Increased mitoses within glandular epithelial cells Increased numbers of apoptotic enterocytes at the surface and in the glands In the colon, inflammatory changes are similar but the most prominent change is increased apoptotic epithelial cells in the glandular epithelium. Human herpesvirus-8 (HHV-8) HHV-8, also known as Kaposi’s sarcoma-associated herpesvirus (KSHV) Strongly associated with Kaposi’s sarcoma Upper gastrointestinal involvement is more common than colonic disease. Lesions are often multifocal and consist of red to violet nodules, plaques, or polyps. Many lesions are submucosal, leading to difficulty in obtaining a satisfactory sample with endoscopic mucosal biopsy.  Histologic features Proliferation of capillary vessels with plump endothelial cells and inconspicuous spindle cell component in early lesions As the lesions progress, the spindled cells are more prominent and forms slit-like vascuar spaces. Extravasated red blood cells, hemosiderin and round eosinophilic globules are variably present Parasitic Infections of the Gastrointestinal Tract Coccidians Important when considering the DDx of diarrhea in AIDS patients All are capable of causing diarrhea (often prolonged) in otherwise healthy patients, especially infants and young children, travelers to developing nations, and individuals who are institutionalized. Transmission: fecal–oral route » directly or via contaminated food and water. Coccidians May be asymptomatic Symptomatic: present with diarrhea +/- fever, weight loss, abdominal pain, and malaise In immunocompetent persons, infection is usually self-limited Immunocompromised patients are at risk for chronic, severe diarrhea, with malabsorption, dehydration, and eventual death. Endoscopic findings are usually absent or mild. Cryptosporidiosis Species most commonly infecting humans include C. parvum, C. hominis, and C. meleagridis. Transmission is through contaminated food and water, and person-to-person spread via the fecal–oral route is common. Patients present with non-bloody, watery diarrhea that may be mucoid. Diarrhea is often protracted and associated with dehydration Cryptosporidiosis Most common in the small bowel - may infect any segment of the GIT Rarely infects the pancreaticobiliary tree Causing sclerosing cholangitis, pancreatitis, or acalculous cholecystitis. Endoscopy is usually normal  Pathologic features Characteristic appearance - 2–5 μm - Basophilic spherical body - Protrudes from the apex of the enterocyte at the luminal surface Have been referred to as “blue beads” in H&E sections They may be found in crypts or in surface epithelium Isosporiasis World-wide distribution More common in tropical / sub-tropical regions It causes infection in both humans and animals. Transmission: contaminated food or water Clinical: present with chronic diarrhea, dehydration, weight loss, anorexia, malaise, and abdominal pain, and malabsorption. Pathologic Features Endoscopy is usually normal Mild mucosal eryethema and granularity may be seen Small bowel is most commonly involved colon and biliary tree may be affected Pathologic Features Histologic changes include villous blunting villous fusion crypt hyperplasia mixed inflammation in the lamina propria, often with prominent eosinophils Isosporiasis Isospora is the largest coccidian (15–20 μm). Can be found within both epithelial cells and macrophages. Inclusions are both perinuclear and subnuclear. Organisms are located within a parasitophorpous vacuole  Microsporidiosis Coccidian least likely to infect immunocompetent persons. Have a worldwide distribution. Human-to-human transmission and fecal/oral spread are also common. Patients present with chronic, non-bloody, non-mucoid diarrhea, with associated dehydration, weight loss, and signs of malabsorption. Symptoms are often worse after meals. Disseminated infection may occur Pathologic features. The small bowel is the most common site of infection. Histologic findings Focal mild villous blunting Patchy lamina propria lymphoplasmacytic infiltrate Variably increased surface intraepithelial lymphocytes Vacuolization of the surface epithelium, and surface epithelial cell disarray. There may be minimal to no tissue reaction. Pathologic features The organisms are present as small spores 2–3 μm in size As well as large plasmodia that are located within the supranuclear cytoplasm of epithelial cells or occasionally lamina propria macrophages (most common with E. intestinalis). Toxoplasma gondii. GIT infection: primarily a disease of immunocompromised hosts In patients with concomitant ocular, central nervous system, cardiac, or pulmonary disease. Present with diarrhea, abdominal pain, vomiting, fever, and weight loss. Gastric and colonic involvement are most common, followed by the small bowel Toxoplasma gondii. Ulcers have been described grossly, with organisms usually located within the ulcer base. Both crescent-shaped tachyzoites As well as tissue cysts containing bradyzoites may be present within tissue sections  MYCOBACTERIUM AVIUM INTRACELLULARE COMPLEX Although M. Avium and M. Intracellulare are different species, but they are referred to as a complex because the infections they cause are so similar GIT is the commonest portal of entry and is twice as common as respiratory involvement. Common when CD 4 < 60 Clinical features are similar to TB Sites of infection: large and small bowel, liver and oesophagus  GASTROINTESTINAL TUBERCULOSIS Any part of the GIT can be affected by TB. The small bowel and the ileocaecal area are most common sites Severity of GIT involvement relates to the severity of pulmonary infections Commonest in individuals with cavitating lung lesions Pathogenesis: Organisms are swallowed and pass through the bowel mucosa without causing a local lesion, they then arrest in regional lymph nodes. Retrograde spread then leads to ulcerative small intestinal lesions Clinical features: chronic non-specific abdominal pain, fever, LOW and malaise  Morphological forms o Ulcerative: 60% cases, present with multiple superficial ulcers o Hypertrophic: 10% of cases, scarring fibrosis and heaped up mass lesions o Ulcerohypertrophic: 30% patients, intestinal wall becomes thickened and ulcerated by an inflammatory mass. Histological features o Areas of ulcerated mucosa o Abscess like neutrophilic infiltrate surrounded by epithelioid histiocytes o Granuloma formation with giant cells and caseous necrosis o Ziehl Neelsen positive AFBs Complications: severe enterocolitis, haemorrhage, perforation, obstruction, fistula formation, strictures and secretory diarrhea.  HIV ASSOCIATED LYMPHOMAS IN THE GIT Extranodal Non-hodgkins lymphomas occur in 10% of HIV infected patients The enteric tract is the most common site accounting for 30% of all HIV associated lymphoma The most common areas of the GIT being the small intestine and the colon 95% of the lymphomas are B-cell lymphomas EBV expression is found in most of these lymphomas References 1. ROBBINS AND COTRAN PATHOLOGIC BASIS OF DISEASE, Ninth Edition 2. General & Systemic Pathology, 5th Edition. J.C.E Underwood & S.S Cross 3. Muir’s Textbook of Pathology, 15th Edition. C. Simon Herrington