Introduction

• infectious diseases are important to hematologists because:

1)     they may simulate malignancies (lymphoma and leukemia)

2)     may directly or indirectly cause anemia or abnormal peripheral blood counts

3)     may involve direct infection of hematopoietic or lymphoid tissues

Infections related to Lymphoid Tissues

• characteristics

1)     lymph node enlargement (deuh!)

2)     pain

Ø  if pain is present generally it characterizes infectious and reactive conditions

Ø  if absent but still have lymphadenopathy, more characteristic of neoplasms

Ø  many exceptions

3)     formation of Buboes may occur

Granulomatous lymphadenitis

• morphologic category that describes any condition the epitheloid granulomas are found in lymph nodes

Tuberculosis

• mycobacterial infections involve nodes either 1^o or as part of a general systemic infection
• 2^o node involvement – occurs when drainage of a primarily-infected organ produces infection of the nodes in the path of the lymphoid drainage of that organ
• SCROFULA = 1^o tuberculous lymphadenitis of the neck
• Morphological hallmark of mycobacterial infection = tuberculoid granuloma

Ø  consists of clusters of polyhedral &/or spindle-shaped histiocytes with abundant, eosinophilic cytoplasm

Ø  Central Necrosis and Langerhans’ multinucleated giant cells may or may not be present

• Acid-fast technique to diagnosis/examine
• Culturing is more sensitive but takes longer (up to 8 weeks); allows for ID of the exact species of mycobacterium and allows for drug sensitivity testing

Histoplasmosis

• causative fungus – Histoplasma capsulatum
• deep fungal infection with granuloma formation
• cames from bird or bat droppings
• endemic in the Mississippi and Ohio river valleys
• Diagnosis – visualization of budding yeasts in hematoxylin/eosin stained sections or via silver impregnation stains

Coccidioidomycosis

• most infectious mycotic organism
• causative agent – Coccidioides immitis (a dimorphic mold like histoplasmosis)
• endemic in the desert Southwest

Other fungal infections

• granulomas admixed with a suppurative (neutrophilic) exudate

Ø  sporotrichosis – Sporothrix schenckii

Ø  American blastomycosis – Blastomyces dermatitidis – Broad Based budding yeast

• Cryptococcus neoformans

Ø  encapsulated yeast that can cause meningoencephalitis in normal individuals but more often in immunocompromised

Ø  present in soil and bird (pigeon) poop

Ø  infection by inhalation

Ø  generally mild and asymptomatic, even while CNS spread is going on

Ø  may form a solitary pulmonary granuloma similar to the coin lesions caused by Histoplasma

• Aspergillus

Ø  mold that causes allergies in healthy persons

Ø  in neutropenic persons – serious sinusitis, pneumonia, and fungemia

Ø  secrete three toxins important in human disease

1.     aflatoxin – made by the species growing on peanuts; may be a major cause of liver cancer in Africa

2.     Mitogillin – potent inducer of IgE

3.     RIP’s – RNA N-glycosidases that depurinate rRNA, resulting in the arrest of protein synthesis

Ø  allergic bronchopulmonary aspergillosis

Ø  sensitization to Aspergillus spors induces Type III and Type IV hypersensitivity reactions

Ø  Colonizing aspergillosis – implies growth of the fungus in pulmonary cavities with minimal or no invasion of the tissues

Ø  “fungus balls”

Ø  Invasive aspergillosis – opportunistic infection confined to immunosuppressed and debilitated

v  primary lesions are in the lungs

v  also widespread hematogenous dissemination to heart valves, brain, kidneys is common

Ø  Aspergillus forms fruiting bodies and septate filaments, branching at acute angles (45 degrees)

• Mucormycosis

Ø  opportunistic infection of neutropenic ,immunocompromised,and ketoacidotic diabetic patients

Ø  caused by the different “bread mold” fungi (inc Mucor, Absidia, Rhizopus-collectively referred to as the Phycomycetes)

Ø  Three primary sites of Mucor invasion are:

1)     nasal sinuses

2)     lungs

3)     GI tract

Ø  in diabetics, the fungus may spread from nasal sinuses to the orbit and brain, giving rise to rhinocerebral mucormycosis

Ø  the phycomycetes 1) cause local tissue damage 2) invade arterial walls  3) penetrate the periorbital tissues and cranial vault.

Cat Scratch Disease

• infectious form of lymphadenitis
• Causative organism – Bartonella henselae – small, pleomorphic cell wall deficient, Gram (-) rod
• Natural habitat – claws of cats
• Clinical presentation

Ø  classical – enlargement of cervical or axillary node draining the area of inoculation

• more common in children
• almost always benign clinically
• minority of cases develop complication including – encephalitis, retinitis, osteomyelitis, arthritis, hepatitis, and pleuritis
• TREATMENT: gentamicin (parental only)
• Can be severe in immunocompromised

Ø  severe skin infections and deep soft tissue masses

Ø  MICRO: lesion are characterized by proliferation of small blood vessels lined by plump endothelial cells that are filled with many of the bacilli = bacillary angiomatosis

Ø  Bacillary peliosis – liver (and sometimes the spleen) develops large blood-filled cystic structures associated with heavily-infected stromal cells

Toxoplasmosis

• causative organism – Toxoplasma gondii – protozoan?
• Infection occurs via the ingestion of uncooked meat or by contact with the feces of infected cats.
• Usually mild and self-limited; organism not seen MICRO in immunocompetent hosts
• MICRO: the lymphadenitis shows marked follicular hyperplasia with reactive germinal center formation; formation of nests of epithelioid histiocytes

Human Immunodeficiency virus

• characterized by a generalized lymphadenopathy that may clinically look like malignant lymphoma
• Early stages of the infection – marked hyperplasia of the follicular B-lymphocytes, producing a follicular hyperplasia
• The follicles gradually decrease in size because the parafollicular B-cells undergo blast transformation and proliferate, yielding a pattern of hyperplastic parafollicular areas surroundind relatively atrophic follicles – here it looks morphologically like a large cell lymphoma
• Final stage of HIV infection – that of totally atrophic lymphoid tissue depleted of lymphocytes

Epstein Barr Virus (EBV)

• DNA virus; member of the herpesvirus group
• Infectious mononucleosis

Ø  acute viral infection characterized by severe pharyngitis, prostration, lymphadenopathy, and fever.

Ø  Common in teenagers and young adults

Ø  Most people sero-positive but probably were asymptomatic

Ø  Complications: hepatitis, splenic rupture, and myocarditis

Ø  Pathology

-        EBV targets the B lymphocyte, stimulated the production and transformation of t-killer lymphocytes.

-        These T cells appear in great numbers in the peripheral blood and have been referred to as Downey cells.

-        The Downey cells are large and have abundant cytoplasm which is more opaque than that of normal lymphocytes; The nucleus is also larger and has more chromatin.

-        The Downey cells are not just a characteristic of EBV infection, but can aid in the diagnosis.

Ø  The reactive lymph nodes can show proliferation of blast-transformed lymphocytes that may be so striking as to morphologically mimic malignant lymphoma

Ø  Serologic findings: heterophile antibodies; can measure with one simple step

Ø  Can now measure IgM-class antibodies to the virus itself

• Burkitt’s Lymphoma

Ø  high grade malignant neoplasm of B lymphocytes that has the fastest growth of any human cancer

Ø  two epidemiologic /clinical varieties

1)     African Burkitt’s lymphoma

• 98% carry the EBV genome

2)     Non-Africa or “American” Burkitt’s lymphoma

• a small minority carry the EBV genome

• Post-transplant lymphoproliferative disorder

Ø  multisystem lymphoma-like proliferation of immunoblasts and plasmacytoid lymphocytes in iatrogenically immunosuppressed organ transplant patients

Ø  thought to be caused by EBV infection of B lymphocytes compounded by the loss of host T cell function brought on by the immunosuppressive therapy

Ø  Morphologically, indistinguishable from malignant lymphoma

Ø  Sme cases behave like high grade malignant lymphomas and kill the patient while others respond to antiviral therapy and regress.

Visceral leishmaniasis

• causative organism – Leishmania donovani or Leishmania tropica – flagellated protozoa that live in histiocytes /macs in the human host
• vector – sandfly – Phlebotomus
• the reticuloendothelial system is the target of the parasitization
• spleen becomes massively enlarged
• MICRO – spear preps show huge numbers of parasites, in their amastigote (w/o flagella) stage.
• Other clinical manifestations: hepatomegaly, fever, gray discoloration of the hands, feet, abdomen, and face
• Persian Gulf War veterans – fatigue, low grade fever, malaise, and occasionally diarrhea

Infections Related to Blood and Bone Marrow

Malaria

• most common form of hemolytic anemia in the world
• causative agents: Plasmodium falciparum, P. vivax, P. ovale, P. malariae
• vector – female Anopheles mosquito
• REMEMBER that P. falciparum does not have an extra-erythrocytic stage and does not form hypnozoites
• P. vivax and P. ovale can cause a late relapse because they have a dormant liver stage (hypnozoites)
• Diagnosis: examination of the peripheral blood smear to look for parasitized erythrocytes
• Clinical presentation: fever, chills, myalgia, malaise, prostration, and headache
• Death can occur as a result of anemia or renal failure
• Blackwater fever – P. falciparum complication in which severe, catastrophic hemolytic anemia occurs

Lymphatic filariasis

• causative organisms – Wuchereria bancrofti and Brugia malayi
• vector – Culex mosquito
• macroscopic adults live in the human lymphatic channels and produce tremendous lymphedema in the drainage areas
• Elephantiasis – scrotum and lower extremities
• Pachyderm-like, hyperkeratatic, fibrotic skin covers the affected areas
• The larval forms may appear in the peripheral blood smear

Human Immunodeficiency Virus

• myelodysplastic syndrome – may produce pancytopenia in excess to that expected by the zidovudine effect
• See HIV lecture notes for more details.

Human T-cell Lymphotropic Virus Type I (HTLV-I)

• cousin of HIV-1; similar modes of transmission
• retrovirus
• infects T-lymphocytes and causes adult T cell leukemia/lymphoma
• also assoc. with a transverse myelopathy that produces spastic paraparesis
• alarming incidence in IV drug users and female prostitutes

Parvovirus B19 (5^th disease)

• etiologic agent of erythema infectiosum
• mild viral exanthem of childhool
• causes nonimmune hydrops fetalis – leads to fetal death
• infects red blood cells only
• transient aplastic crisis

Tags: Aspergillus, Blackwater fever, Burkitt's Lymphoma, Coccidioidomycosis, falciparum, granulomas, Granulomatous lymphadenitis, heterophile, Histoplasmosis, Human Immunodeficiency Virus, hypnozoites, lymph node enlargement, lymphadenopathy, Lymphatic filariasis, Lymphoid Tissues, Lymphotropic Virus, Malaria, neoplasms, Parvovirus, Tuberculosis, Visceral leishmaniasis

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