Onc Final 2.2

features of bacterial infections causing lymphadenopathy?

• gram negative (pink) bacilli/coccobacilli

• facultative IC + facultative anaerobe

• elevated IgM = 1st sign of infection

• yersinia pestis, francisella tularensis, bartonella henselae

yersinia pestis vector? symptoms? growth?

• flea/rodent → bubonic plague

  • T3SS virulence factor = direct injection

• fluctuant LN (buboes); vessel blockage → gangrene

• grows on blood, chocolate, macconkey agar → fried egg colonies; bipolar staining pattern (safety pin) w/ giemsa

francisella tularensis vector? symptoms? types?

• rabbit/tick → tularemia

  • non-motile

• LAD (cervical), fever, myalgia, cough, abdominal pain, diarrhea

• ulceroglandular (tick bite → papule → ulcer) + oculorglandular (contaminated fluid in eye → purulent conjunctivitis)

yersinia pestis and francisella tularensis medication?

• ciprofloxacin/levofloxacin (severe, tularemia) OR streptomycin/gentamicin (mild tularemia)

  • both if pneumonic/septicemic

• doxycycline

bartonella henselae vector? symptoms? meds?

• cat/flea → cat scratch disease

  • flagellated (motile)

• enlarged nodes close to site of flea bit/cat scratch

  • severe immunocompromised pts (via HIV) → bacillary angiomatosis/BA (vasc. proliferation in skin + LN)

• warthin-starry stain

• azithromycin (LAD) + rifampin (HSM) OR doxycycline w/ rifampin (neuroretinitis)

human herpes virus-8 (kaposi sarcoma) genome? family? symptoms?

• enveloped dsDNA, herpesviridae

• primary infection in immunocompromised pts (AIDS)

  • KS = lesions on skin (similar to BA), GI, LN

• epithelioid + spindle cells (histopathology) → mostly lymphocytes/plasma cell

epstein-barr virus (HHV-4) genome? family? symptoms? unique features?

• enveloped dsDNA, herpesviridae

• LAD, splenomegaly, pharyngitis (classic infectious mono)

  • atypical (reactive) lymphocytes

  • replicate in B cell, latent in memory B cell, grow + immortalize B cell

• VCA-IgG → IgM, EA, heterophile Ab = (+) monospot

• burkitt lymphoma → VCA-IgG, EA, EBNA

cytomegalovirus (HHV-5) genome? family? symptoms? unique feature?

• enveloped dsDNA, herpesviridae

• less severe LAD + pharyngitis, atypical lymphocytosis (T-cell)

  • persistent, latent infection

• heterophile-negative mono

human papillomavirus (HPV) genome? family? symptoms? genome structure? unique features?

• naked DNA (circular), papillomaviridae

• LAD, cervical cancer, leads to warts/papillomas

• E6 binds p53, E7 binds Rb, L1= capsid protein,

• virus-like particle vaccine; test w/ pap smear

human T-cell lymphotropic virus (HTLV) genome? family? symptoms? types? associated with?

• enveloped + RNA, retroviridae

• LAD, nodular rash affect scalp, axillae, groin

• TAX = HTLV1 (red papule/nodule + plaque), HAM= HTLV2 (demyelinating)

• associated w/ ATLL: lymphocytes w/ condensed chromatin + multilobed nuclei/flower

lymphoma description? categorization?

• neoplasm from LN (painless LAD) → variable presentation (e.g atypical sites, leukemic presentation)

• Hodgkin → localized, single group of nodes w/ contiguous spread (B Sx + LAD)

• non-Hodgkin → multiple LN w/ EN involvement; non-contiguous spread (children + adults)

hodgkin lymphoma risk factors? composition? staging?

• 20 or 55+, prior EBV infection, autoimmune disease, immunosuppressants

• reed-sternberg cells (bilobed nuclei/owl eyes) expressing CD15,30 (membranous golgi) → release cytokines → generate reactive cells

  • B cell marker (-)

• single LN region/site → 2+ → bilateral involvement → diffuse involvement

subtypes of hodgkin lymphoma?

• nodular sclerosis** → common, collagen bands sclerose nodes, mediastinal mass

• mixed cellularity → eosinophil (IL5), neutrophil, MO, PC

• lymphocyte rich → small lymphocyte; malignant = range of morph

• lymphocyte depleted → diffuse reticulin fibrosis w/ hypocellular infiltrate; atypical neoplastic

• nodular lymphocyte predominant → no RS (lack CD15/30); popcorn cell w/ CD20 (B cell markers + CD45)

non-hodgkin lymphoma association? symptoms?

• autoimmune diseases (sjogren, hashimoto, AIDs), viral infection (HIV, EBV, HTLV), immunosuppressive therapy

• rapidly progressive mass, painless LAD, splenomegaly, B Sx (weight loss, night sweat, fever)

• B cell origin + derive from germinal follicle (express CD10,20)

  • whole mass is neoplastic cells

burkitt lymphoma type? etiology? characteristics?

• peripheral/mature B cell neoplasm; int. B cell (more common in kids)

• t(8;14) → inc. c-MYC (cell growth); mature B cell marker (CD10, 20)

• GC; starry sky (via tingible MO + mitotic figures); EBV

• HIV associated (LN or EN), african (large jaw) or sporadic (pelvic/abdominal lesion → ileocecal + peritoneum)

• Tx w/ rituximab (anti CD20)

burkitt lymphoma TLS risk?

• rapid cell breakdown

  • hyperK/P

  • hyperuricemia

  • hypoCa

  • DIC

• prevention w/ IV hydration, allopurinol (inhibits XO= dec. uric acid), rasburicase

diffuse large B cell lymphoma (DLBCL) type? etiology? characteristics?

• peripheral/mature B cell neoplasm (from CLL/Richter or follicular)

• BCL2/6, MYC overproduction> gene arrangement; mature B cell marker (CD10, 20)

• most common; ill defined, effacement → aggressive

  • seen in HIV pts (AIDS defining), in testes + CNS

• Tx w/ R CHOP (rituximab, cyclophosphamide, doxorubicin/hydroxy, vincristine/oncovin, prednisone)

follicular lymphoma type? etiology? characteristics?

• peripheral/mature B cell neoplasm (small B cell) → GC B cell

• t(14;18) → inc. BCL2 (inhibit apoptosis = lack tingible MO); mature B cell marker (CD10, 20)

• indolent w/ painless “waxing/waning” LAD

  • reactive/crowded follicles, diffuse effacement, EN extension

mantle cell lymphoma type? etiology? characteristics?

• peripheral/mature B cell neoplasm (small B cell) → naive mature B cell

• t(11;14) → inc. cyclin D1 (inc. G1/S); mature B cell marker (CD 20, 5)

• post-germinal; aggressive form → pt. present w/ late stage

  • expand to adj. follicle

  • males more

EN marginal cell lymphoma type? etiology? characteristics?

• peripheral/mature B cell neoplasm (small B cell) → mature B cell

• t(11;18); mature B cell marker (CD19, 20, 22)

• post-GC; associated w/ chronic inflammation → sjogren, chronic gastritis (MALToma, H pylori)

  • mucosal ulceration, EBER ISH, CD56 + perforin

  • regression w/ removal of inciting agent

adult T cell lymphoma (ATLL) type? etiology? symptoms?

• peripheral/mature T/NK cell neoplasm

• cause via HTLV + IV drug use; CD2-5

• LAD, cut. lesions, lytic bone lesions, inc. Ca

  • common in japan, west africa, caribbean (DONT CONFUSE w/ MM)

cutaneous T cell lymphoma type? etiology? types?

• peripheral/mature T/NK cell neoplasm

• T cell neoplasm affecting skin/blood, LN or viscera

• mycosis fungoides (local) or sezary syndrome (diffuse)

  • erythematous patch → plaque → tumor; cerebriform nuclei

plasma cell dyscrasias? diagnostic tools?

• disorders characterized by proliferation of single plasma cell clone, overproduction of monoclonal Ig

• serum → SPE (quantifies M protein = amt. of myeloma), SIE (characterizes M protein = IgG or IgA), light chains (better than urinalysis)

• urine → protein electrophoresis (ID + quantify BJP= free light chain), immunofixation electrophoresis (characterizes BJP as k or λ)

monoclonal gammopathy of undetermined significance (MGUS) overproduction? clinical features? BM biopsy?

• any Ig, M spike w/o other MM symptoms

• asymptomatic; risk progression to MM

• <10% monoclonal plasma cells

multiple myeloma (MM) overproduction? clinical features? BM biopsy?

• IgG>IgA>Ig light chain (M spike)

• sheets of malignant plasma cells replace hematopoietic act. in BM

  • CRAB: hyperCa (via RANK), renal insufficiency (BJP), anemia, bone lytic lesion (back pain, via RANK), infection risk, primary amyloidosis (light chain deposit)

• >10% monoclonal plasma cells, clockface chromatin + intracytoplasmic inclusions

  • smear → rouleaux formation

• smoldering → asymptomatic

waldenstrom macrogloulinemia (WM) overproduction? clinical features? BM biopsy?

• IgM (w M spike)

• anemia, LAD, hyperviscosity (via IgM = def. coagulation), HSM, peripheral neuropathy, visual defect

• >10% monoclonal B cells w/ plasma cell features + intranuclear pseudo inclusions w/ IgM; BJP

light chain amyloidosis overproduction? clinical features? BM biopsy?

• free light chains (k or λ) → accumulates via altered physiochemical property

• nephrotic syndrome, restrictive cardiomyopathy, macroglossia, neuropathy

• variable plasma cell burden; congo red stain (shows amyloid deposits w/ birefringence)

solitary plasmacytoma overproduction? clinical features? BM biopsy?

• IgG, light chain (localized)

• localized bone pain or mass

• clonal plasma cells in isolated lesion

heavy chain disease overproduction? clinical features? BM biopsy?

• truncated heavy chains (a,y,u) w/o light chains

• diarrhea, weight loss, LAD (a-HCD), respiratory or systemic symptoms

• abnormal plasma cells produce heavy chains; often diffuse marrow infovlemetn

langerhan cell histiocytosis mechanism? symptoms? characteristics?

• group of neoplastic proliferative disorders of langerhan cells (DC → APC in skin)

• lytic bone lesion, skin rash, otitis media involving mastoid bone

• “coffee bean” nuclei + birbeck granules (tennis racket) on EM w zipper like appearance, pentalaminar structure

mastocytosis mechanism? types?

• neoplastic clonal proliferation of mast cells → KIT mut.

• cutaneous → urticaria pigmentosa/maculopapular cut. mastocytosis, diffuse cut. mastocytosis, mastocytoma of skin

• systemic → less burden (indolent; BM), higher burden (smoldering; hematological neoplasm association; aggressive; mast cell leukemia)

rosai-dorfman mechanism? symptoms? characteristics?

• reactive disorder; medullary/cortical sinus histiocytosis w/ massive LAD; emperipolesis (engulf intact cells)

• painless, massive LAD; bilateral cervical fever, weight loss

• can involve EN sites + present w/ multiple concurrent sites of involvement

  • emperipolesis (cytoplasm contains intact engulfed cells)

  • CD68 (histiocytosis), S100

hemophagocytic lymphohistiocytosis mechanism? types? symptoms?

• reactive condition characterized by enhanced phagocytosis

• familial (inability to regulate MO killing via NK and/or T cell = widespread proliferation of act. MO w/in RES) or acquired (via infections like EBV)

  • skin rash, fever, inc. IL2, act. MO effacing + dec. hematopoiesis

• acute febrile illness, HSM

dermatomyositis hypertrophic, osteoarthropathy mechanism? associated tumor? ?

• heliotrope rash, gottron papules, prox. weakness

  • ovarian, lung, pancreatic

• clubbing, periostitis

  • lung adenocarcinoma

MSK/Derm

acanthosis nigricans, lesler-trelat mechanism? associated tumors?

• velvety hyperpigmented plaques

• sudden eruption of multiple seborrheic keratoses

• GI adenocarcinoma

MSK/Derm

hypercalcemia, pure red cell aplasia, trosseau syndrome mechanism? associated tumors?

• inc. Ca → stones, bones, groans, psychiatric overtones

  • squamous cell carcinoma (lung, head/neck), breast, renal

• selective absence of erythroid precursor → thymoma

• recurrent superficial thromboses → pancreatic, lung, gastric

endocrine

cushing syndrome, SIADH mechanism? associated tumors?

• inc. cortisol, central obesity, striae, HTN

• hyponatremia, euvolemia, low serum osmolality

• small cell lung carcinoma (SCLC)

endocrine

opsoclonus-myoclonus ataxia, subacute cerebellar degeneration mechanism? associated tumors?

• chaotic eye movement → neuroblastoma (child), breast/lung (adult)

• ataxia, dysarthria, nystagmus → gynecologic, breast, lung

neuromuscular

lambert-eaton myasthenia, limbic encephalitis mechanism? associated tumors?

• prox. muscle weakness, autonomic symp., improve w/ use

• multifocal CNS symptoms

• small cell lung carcinoma (SCLC)

neuromuscular

carcinoid syndrome mechanism? associated tumors?

• flushing, diarrhea, bronchospasm, inc. 5-HIAA

• neuroendocrine tumor (GI, lung)