Pathology+of+Vascular+and+Cardiac+Tumors%2C+Text.pdf

Pathology of Vascular and Cardiac Tumors Michael Yakubovskyy, MD, PhD Professor of Pathology Ross University School of Medicine 1  Classification Vascular Tumors Cardiac Tumors Tumor-lik...

Pathology of Vascular and Cardiac Tumors Michael Yakubovskyy, MD, PhD Professor of Pathology Ross University School of Medicine 1  Classification Vascular Tumors Cardiac Tumors Tumor-like Vascular ectasias Cardiac myxoma Benign tumors conditions Bacillary angiomatosis Rhabdomyoma Hemangioma Hemangioblastoma Sarcoma, any type Benign tumors Malignant tumors Lymphangioma Metastatic tumors Glomus tumors Tumors of Kaposi sarcoma intermediate Hemangioendothelioma malignancy Hemagiosarcoma Malignant tumors Lymphangiosarcoma 2  Learning Objectives Compare and contrast the following vascular and cardiac tumors and tumor-like vascular lesions - LO1. Tumor-like vascular conditions: vascular ectasia and bacillary angiomatosis - LO2. Benign vascular tumors: hemangioma, hemangioblastoma, lymphangioma, and glomus tumor - LO3. Vascular tumors of intermediate malignancy: Kaposi sarcoma - LO4. Malignant vascular tumors: hemangiosarcoma and lymphangiosarcoma - LO5. Benign cardiac tumors: myxoma and rhabdomyoma in terms of - Epidemiology: age, sex, and predisposing factors - Organs affected - Clinicopathologic presentation - Treatment - Prognosis 3 LO1. Tumor-like vascular conditions: vascular ectasia and bacillary angiomatosis Vascular Ectasia Localized vascular ectasia: dilation of preexisted blood vessels; not a neoplasm - Clinicomorphologic types Telangiectasia - Including spider telangiectasia Nevus flammeus - Including port-wine stain Generalized hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease) 4 LO1. Tumor-like vascular conditions: vascular ectasia and bacillary angiomatosis Telangiectasia Dilation of single small blood vessels in the skin or mucous membranes 5 LO1. Tumor-like vascular conditions: vascular ectasia and bacillary angiomatosis Spider Telangiectasia Radial array of dilated subcutaneous arteries/arterioles (tentacles) around a central core - DDx with congenital lesions: pressure applied to the central core causes the tentacles to disappear Location: face, neck, and upper chest Etiology - Hyperestrinism in pregnancy - Liver cirrhosis 6 LO1. Tumor-like vascular conditions: vascular ectasia and bacillary angiomatosis Spider Telangiectasia: Presentation 7 LO1. Tumor-like vascular conditions: vascular ectasia and bacillary angiomatosis Nevus Flammeus A birthmark, seen in 25 – 50% of newborns Congenital capillary malformation Predominant neck and head location Subtypes - “Stork bite”on the nape and “angel kiss” on the face Usually regresses spontaneously - Port wine stain: red/ruby, rough Does not regress 8 LO1. Tumor-like vascular conditions: vascular ectasia and bacillary angiomatosis “Stork Bite” and “Angel Kiss” 9 LO1. Tumor-like vascular conditions: vascular ectasia and bacillary angiomatosis Port-Wine Stain A type of nevus flammeus, which - Does not regress - Grows with a child - Thickens the skin surface May be a component of Sturge-Weber syndrome - Port-wine stain in trigeminal nerve distribution - Leptomeningeal angiomas/malformations Brain involvement: seizures, hydrocephalus, mental retardation 10 LO1. Tumor-like vascular conditions: vascular ectasia and bacillary angiomatosis Port Wine and Stain 11 LO1. Tumor-like vascular conditions: vascular ectasia and bacillary angiomatosis Sturge-Weber Syndrome 12 LO1. Tumor-like vascular conditions: vascular ectasia and bacillary angiomatosis Hereditary Hemorrhagic Telangiectasia Syn.: Osler-Weber-Rendu disease An ADD, mutations in TGF-ß signaling pathway Presentation - Multiple telangiectasias located in the skin and mucosal membranes (nasal, oral, respiratory, GI, urinary) Seen by naked eye - May be present at birth or appear later Complications: rupture —> bleeding (e.g., epistaxis) 13 LO1. Tumor-like vascular conditions: vascular ectasia and bacillary angiomatosis Hereditary Hemorrhagic Telangiectasia: Presentation 14 LO1. Tumor-like vascular conditions: vascular ectasia and bacillary angiomatosis Bacillary Angiomatosis Focal vascular proliferation, not a neoplasm Primarily affected organs: skin, bone, brain Immunocompromized host Opportunistic infection: Bartonella species - B. henselae (the cause of cat-scratch disease) - B. quintana (the cause of trench fever) Pathogenesis: bacteria —> production of HIF-1α by infected host tissues —> production of VEGA —> vascular proliferation Treatment: antibiotics 15 LO1. Tumor-like vascular conditions: vascular ectasia and bacillary angiomatosis Bacillary Angiomatosis: Presentation B: Identification of Bartonella with Wartin-Starry 16 (silver) stain LO2. Benign vascular tumors: hemangioma, hemangioblastoma, lymphangioma, and glomus tumor Hemangioma Any age Location: skin > visceral organs (liver) Classification - Capillary hemangioma Subtype: juvenile (Robbins) or infantile (Uptodate) hemangioma - Infancy and childhood - Often regresses spontaneously by the age of 7 - Cavernous hemangioma - Pyogenic granuloma: inflamed hemangioma Subtype: granuloma gravidarum: pregnant women, gums 17 LO2. Benign vascular tumors: hemangioma, hemangioblastoma, lymphangioma, and glomus tumor Capillary Hemangioma: Morphology Gross appearance: red-to-blue nodule Histology - Closely packed thin-walled capillaries filled with blood and lined by benign endothelium - Proliferation of benign endothelial cells between capillaries No capsule 18 LO2. Benign vascular tumors: hemangioma, hemangioblastoma, lymphangioma, and glomus tumor Capillary Hemangioma: Morphology Infantile hemangioma 19 LO2. Benign vascular tumors: hemangioma, hemangioblastoma, lymphangioma, and glomus tumor Cavernous Hemangioma More often visceral distribution, if compare with capillary hemangioma Histology: large cavernous channels lined by the endothelium filled with RBCs - No capsule Significance: bleeding, especially from cavernous hemangioma of the liver 20 LO2. Benign vascular tumors: hemangioma, hemangioblastoma, lymphangioma, and glomus tumor Cavernous Hemangioma, Liver: Presentation 21 LO2. Benign vascular tumors: hemangioma, hemangioblastoma, lymphangioma, and glomus tumor Pyogenic Granuloma (L), Granuloma Gravidarum (R), Histology 22 LO2. Benign vascular tumors: hemangioma, hemangioblastoma, lymphangioma, and glomus tumor VHL Syndrome and Hemangioblastoma VHL syndrome/disease: an ADD; loss/inactivation of VHL tumor-suppressor gene on chr. 3p Manifestations - Hemangioblastoma: benign vascular tumor that produces cysts as within as outside itself Location: cerebellum, brain stem, spinal cord, and retina - Risk of renal cell carcinoma - Risk of pheochromocytoma and other tumors 23 LO2. Benign vascular tumors: hemangioma, hemangioblastoma, lymphangioma, and glomus tumor Hemangioblastoma in VHL Syndrome: Distribution, MRI (T1, Gadolinium-Enhanced), and Gross Presentation 24 LO2. Benign vascular tumors: hemangioma, hemangioblastoma, lymphangioma, and glomus tumor Lymphangioma A lymphatic analog of hemangioma Children Skin and subcutis: neck, head, and axillae Morphologic types (analogous to hemangioma) - Capillary lymphangioma - Cavernous lymphangioma Cystic hygroma on the neck 25 LO2. Benign vascular tumors: hemangioma, hemangioblastoma, lymphangioma, and glomus tumor Glomus Tumor (Glomangioma) A benign tumor from the glomus body - Glomus body: a cluster of arteriovenous anastomoses involved into thermoregulation lined by glomus cells (modified smooth muscle cells) Usual location: fingers, toes, palms, feet, often under the fingernails Features: paroxysmal pain, cold sensitivity 26 LO2. Benign vascular tumors: hemangioma, hemangioblastoma, lymphangioma, and glomus tumor Glomus Tumor: Presentation 27 LO3. Vascular tumors of intermediate malignancy: Kaposi sarcoma Kaposi Sarcoma (KS) Origin: (?) lymphatic endothelium Borderline clinical behavior - Usually asymptomatic - Does not recur after excision - Good response to radio- and chemotherapy - May invade and metastasize Etiology: HHV-8 (syn.: KSHV) Transmission: sexual intercourse, blood transfusion, saliva, etc. Skin is primarily affected 28 LO3. Vascular tumors of intermediate malignancy: Kaposi sarcoma KS: Variants Chronic (European/classic) KS Lymphadenopathic (African/endemic) KS Transplant-associated KS AIDS-associated KS - Dramatic decline in incidence with introduction of antiretroviral treatment 29 LO3. Vascular tumors of intermediate malignancy: Kaposi sarcoma KS: Gross Appearance Skin lesion: pink-red-purple patch—> plaque —> nodule - Patch: flat lesion - Plaque: elevated flat-topped lesion - Nodule: elevated dome-shaped lesion Visceral lesion: nodule 30 LO3. Vascular tumors of intermediate malignancy: Kaposi sarcoma KS: Gross Presentation 31 LO3. Vascular tumors of intermediate malignancy: Kaposi sarcoma KS: Histology Cords of pleomorphic spindle-shaped cells - Resemble fibroblasts, but do not produce collagen Small vessels and slit-like spaces - Rows of RBCs Interstitium: RBCs, hemosiderin, macrophages, and plasma cells 32 LO3. Vascular tumors of intermediate malignancy: Kaposi sarcoma KS: Histologic Presentation 33 LO4. Malignant vascular tumors: hemangiosarcoma and lymphangiosarcoma Hemangiosarcoma Origin: endothelium Adults, M = F Location: skin, soft tissues, breast, and liver Etiology, known: irradiation, chemicals - Hepatic hemangiosarcoma: arsenic, thorotrast, and polyvinyl chloride (PVC) Locally invasive; highly metastatic Poor prognosis: 5-yr survival rate —> “0” 34 LO4. Malignant vascular tumors: hemangiosarcoma and lymphangiosarcoma Hemangiosarcoma: Morphology Gross appearance - Large fleshy mass - No distinct borders - Hemorrhages and necrosis Histology - Sheets of pleomorphic cells - High mitotic activity - Vascular-like channels with RBCs - (+)CD31: endothelial marker Asterisk: liver tissue; arrows: tumor 35 LO4. Malignant vascular tumors: hemangiosarcoma and lymphangiosarcoma Lymphangiosarcoma Etiology: chronic lymphedema - Mainly after radical mastectomy - Latent period: ≈ 10 yrs Morphology: resembles hemangiosarcoma Prognosis: similar to hemangiosarcoma 36 LO5. Benign cardiac tumors: myxoma and rhabdomyoma Cardiac Myxoma The most common primary cardiac tumor Gross appearance - Usual location: left atrium - 5 – 6 cm in diameter, with a short stalk - May obstruct the mitral valve orifice Histology - Stellate or spindle-shaped cells embedded in - Myxoid stroma 37 LO5. Benign cardiac tumors: myxoma and rhabdomyoma Cardiac Myxoma: Clinical Correlates Constitutional symptoms and signs: systemic inflammatory response syndrome due to production of IL-6 (fever, fatigue, weight loss, anemia, elevated ESR and CRP) Complications - Valvular obstruction - Systemic embolization with brain infarcts 38  LO5. Benign cardiac tumors: myxoma and rhabdomyoma Cardiac Myxoma: Gross Presentation 39 LO5. Benign cardiac tumors: myxoma and rhabdomyoma Cardiac Myxoma: Histo Presentation 40 LO5. Benign cardiac tumors: myxoma and rhabdomyoma Cardiac Rhabdomyoma The most common childhood cardiac tumor Predisposition/genetics - ½ is associated with tuberous sclerosis complex (TSC) covers in NP2 module - ½: sporadic Prognosis: may regress spontaneously 41 LO5. Benign cardiac tumors: myxoma and rhabdomyoma Cardiac Rhabdomyoma: Morphology Usually multiple Usual location: ventricular wall Histology: large cardiomyocytes laden with glycogen granules —> “spider cells” 42  Summary 1. Spider teleangiectasia:... 2. Port-wine stain including Sturge-Weber syndrome: … 3. Hereditary hemorrhagic teleangiectasia: … 4. Bacillary angiomatosis: … 5. Capillary hemangioma: … 6. Infantile hemangioma: … 7. Pyogenic granuloma: … 8. Cavernous hemangioma: … 9. von Hippel Lindau syndrome:... 10.Glomus tumor:... 11.Kaposi sarcoma:... 12.Hemangiosarcoma: … 13.Lymphangiosarcoma:... 14.Cardiac myxoma: … 15.Cardiac rhabdomyoma: … 43 The End 44