Vascular TumorsBENIGN TUMORS AND TUMOR-LIKE CONDITIONS :Hemangioma: Most commonly are localized, however someinvolve large segments of body such asan entire extremity (called angiomatosis). The majority are superficial lesions (head or neck),but may occur internally (one third in liver). Malignant transformation occurs rarely if at all. Constitute 7% of all benign tumorsin infancy and childhood.
Capillary Hemangioma: Skin , subcutaneous tissues, and mucousmembranes of oral cavities and lips. May also occur in liver, spleen, and kidneys. The "strawberry type" of capillary hemangioma(juvenile hemangioma) of skin of newborn:-o Extremely common (1 in 200 births).o May be multiple.o Grow rapidly in first few months.o Begin to fade when the child is between ages1 and 3 years.o Regress by age 7 in 75% to 90% of cases.
Morphology: Gross:o Size : few millimeters to several centimeters.o Bright red to blue.o Level with surface of skin or slightly elevated.o Occasionally, they are pedunculated. Microscope :o Closely packed thin-walled capillaries which areblood-filled and lined by flattened endothelium,separated by scanty connective tissue stroma.
Infantile capillary hemangioma ,Photograph shows a strawberry-coloredlesion and swelling of left cheek.capillary hemangioma: numerousthin-walled blood-filled capillaries areseen in upper dermis(H&E).
Cavernous Hemangioma: Less common than capillary variety. Usually larger, less well circumscribed, andmore involve deep structures. Locally destructive and show no tendency to regress. Those in brain are most threatening. In von Hippel-Lindau disease: cavernoushemangiomas in cerebellum, brain stem, and eye;along with cystic neoplasms in pancreas and liver.
Morphology: Gross:o Red-blue, soft, spongy mass 1 to 2 cm in diameter.o Rarely giant forms. Microscope:o Large cavernous vascular spaces,partly or completely filled with blood,separated by scanty connective tissue stroma.o Intravascular thrombosis with associateddystrophic calcification is common.
Pyogenic Granuloma (Lobular Capillary Hemangioma): Exophytic red nodule attached by a stalk to skinand gingival or oral mucosa. Bleeds easily and often ulcerated. One third of lesions develop after trauma. Histologicaly : lobules of proliferating capillaries ,accompanied by extensive edema, and acute andchronic inflammatory infiltrate; resemblingexuberant granulation tissue. Recurrence occurs infrequently.
Granuloma gravidarum:o Pyogenic granuloma that occurs in gingiva of1% of pregnant women.o Regresses after delivery.o Highlight the role of estrogen in vascular growthand proliferation.pyogenic granuloma of index finger well developed lobular pattern.
Lymphangiomas:Lymphatic analog of hemangiomas of blood vessels.Capillary Lymphangioma: Occur subcutaneously in head and neck and in axilla. Slightly elevated or pedunculated lesions,1 to 2 cm in diameter, blister-like blebs that arefilled with exudate. Histologically: network of endothelium-lined lymphspaces beneath epidermis and distinguished fromcapillary hemangioma only by absence of blood cells.
Cavernous lymphangioma (Cystic hygroma): Occurs in children in neck or axilla, rarelyretroperitoneally. Occasionally achieve considerable size (up to 15 cm). Massively dilated cystic lymphatic spaces lined byendothelial cells and separated by scant interveningconnective tissue stroma that often containslymphoid aggregates. Cystic hygroma of neck occur in Turner syndrome .
Glomus Tumor (Glomangioma): Benign painful tumor. Arise from modified smooth muscle cells ofglomus body (a specialized arteriovenousanastomosis that is involved in thermoregulation). Most commonly found in distal portion of digits,especially under fingernails. Excision is curative.Morphology: Gross:o Usually small (under 1 cm in diameter).o Slightly elevated, rounded, red-blue, firm nodules.
Microscope :o Branching vascular channels separated byconnective tissue stroma.o The stroma contains aggregates, nests,and masses of specialized glomus cells thattypically arranged around vessels.o Individual cells are small, regular in size, roundor cuboidal, with scant cytoplasm and featuresvery similar to smooth muscle cells on electronmicroscopy.
Vascular Ectasias: Not true neoplasms. Include group of lesions characterized bylocalized dilation of preexisting vessels.Nevus Flammeus: Birth mark. Most common form of ectasia. Head and neck. Flat and color (light pink to deep purple). Histologically: dilation of vessels in dermis. The majority ultimately fade and regress.
Special form of nevus flammeus (port-wine stain):o Grow proportionately with child.o Thicken the skin surface.o No tendency to fade.Spider Telangiectasia (Arterial Spider): Pulsatile dilated subcutaneous arteries or arterioles. Blanches when pressure is applied. Face , neck, and upper chest. Most frequent in pregnant womenand in patients with liver cirrhosis. Hyperestrinism found in these twosettings is believed to play a role.
Hereditary Hemorrhagic Telangiectasia(Osler-Weber- Rendu Disease): Autosomal dominant disease. Genetic malformations consistingof dilated capillaries and veins. Present from birth and distributedover skin and mucous membranesof oral cavity, lips, respiratory, GIT,and urinary tracts. Rupture may occur causing serious nosebleeds,bleeding into gut, or hematuria.
Bacillary Angiomatosis : First described in AIDS patients. An opportunistic infection manifest as vascularproliferations that clinically resemble tumors. Involve skin, bone, brain, and other organs. Caused by infection with gram-negative bacilliof Bartonella family (Bartonella henselae, andB. quintana). These bacilli are difficult to be cultivated in lab. Can be demonstrated by molecular methods(polymerase chain reaction ). How these organisms cause vessel lesions is unclear.
Morphology: Gross : cutaneous one to numerous red papulesand nodules, or rounded subcutaneous masses. Microscope :o Proliferation of capillaries that exhibit epithelioidendothelial cells with nuclear atypia and mitoses.o Numerous stromal neutrophils, nuclear dust , and purplishgranular material consisting of causative bacteria.
INTERMEDIATE-GRADE (BORDERLINE, LOW-GRADEMALIGNANT) TUMORS:Kaposi Sarcoma:Four forms : Chronic, classic , or European KS:o Occurs primarily in older men of Eastern Europe.o Not associated wth HIV.o Remain asymptomatic and localized to skin andsubcutaneous tissue.o Viscera or mucosa involved only in 10% of patients.
Lymphadenopathic:o Also called African or endemic KS.o Common in Africa.o Skin lesions are sparse.o HIV-negative and HIV-positive cases occur. Transplant-associated(immunosuppression-associated)KS:o Occurs several months to few years postoperatively.o Aggressive.o Involving lymph nodes, mucosa, and visceral organsin half of patients.o Skin lesions may be absent. AIDS-associated KS:o Involvement of lymph nodes and gut and widedissemination occur early in course.
Morphology:Three stages identified: patch, plaque, and nodule. Patch stage:o Pink to red to purple solitary or multiple maculesthat are confined to distal lower extremities or feet.o Microscopically: dilated, irregular, and angulatedblood vessels lined by endothelial cells ; withinterspersed infiltrate of lymphocytes, plasma cells,and macrophages.
Plaque stage:o Over time lesions spread proximally andconvert into larger, violaceous, raised plaques.o Microscopically: Dermal dilated jagged vascular channelslined by plump spindle cells with perivascularaggregates of similar spindled cells. Scattered between vascular channels areextravasated red blood cells, hemosiderin-ladenmacrophages, lymphocytes, and plasma cells. Pink hyalin globules of uncertain nature inspindled cells and macrophages. Mitotic figures may be present.
Nodule stage:o At still later stage , lesions become nodularand more neoplastic.o Microscopically: Sheets of plump proliferating spindle cellsin dermis or subcutaneous tissues. In this cellular background are scattered smallvessels and slit-like spaces that contain red cells. Marked hemorrhage, lymphocytes, and macrophagesmay be admixed with this cellular background. Mitotic figures are common, as are the round pinkcytoplasmic globules.o Often accompanied by involvement of lymph nodesand viscera.
Microscopy shows spindle cells and slit like vascularchannels containing erythrocytes (H & E ×400)
Pathogenesis: In 1994, DNA fragments of a previously unrecognizedherpesvirus (Human Herpes Virus 8 [HHV-8] alsoknown as KS-associated Herpes Virus [KSHV])isolated from skin lesion of patient with AIDS. Subsequent studies have shown that regardless ofclinical subtype 95% of KS lesions are infected withKSHV. KSHV is transmitted sexually and by poorlyunderstood nonsexual routes. KSHV proteins disrupt the control of cellularproliferation and prevent apoptosis of endothelialcells, through production of p53 inhibitors anda viral homologue of cyclin D.
Clinical Course: Classic form of KS: resection of primary lesionsand recurrences is usually an adequate treatment,yielding an excellent prognosis. Radiation: for multiple lesions in a restricted area. Chemotherapy: for extensive or disseminated disease. In immunosuppression-associated KS: withdrawalor reduction of immunosuppression, supplementedwith chemotherapy or radiotherapy is often effective. In persons with AIDS: antiretroviral therapy.
Hemangioendothelioma: Representative of this group is epithelioidhemangioendothelioma:o Vascular tumor occurring around medium-sizedand large veins in soft tissue of adults.o Well-defined vascular channels are inconspicuous,and tumor cells are plump and often cuboidal,thus resembling epithelial cells.o Clinical behavior is variable: most are cured byexcision, but 40% recur, 20% to 30% metastasize,and 15% of patients die of the tumors.
Epitheliod hemangioendothelioma of liver,the epithelioid tumor cells grow within dilatedsinusoids with intervening collagenous fibrosis.The tumor cells of epithelioidhemangioendothelioma grow in sinusoids(long arrows) among non-neoplastichepatocytes as shown byImmunohistochemical staining for Hep-Par1(arrowhead).
MALIGNANT TUMORS:Angiosarcoma: Varying from highly differentiated tumors thatresemble hemangiomas (hemangiosarcoma) ;to those difficult to distinguish from carcinomaor melanoma. Occur in both sexes, more often in older adults. Anywhere in body but most commonly in skin,soft tissue, breast, and liver. Hepatic angiosarcomas are associated withcarcinogens: arsenic , Thorotrast , and polyvinylchloride (PVC).
May also arise in setting of lymphedema 10 yearsfollowing radical mastectomy for breast cancer. In such cases, the tumor arises from dilatedlymphatic vessels (lymphangiosarcoma). Angiosarcomas can be induced by radiation. May be associated with foreign material introducedinto body (either iatrogenically or accidentally). Clinically, angiosarcomas show local invasion anddistal metastasis. The majority of patients have poor outcome withvery few surviving 5 years.
Morphology: Gross :o Cutaneous angiosarcoma may begin as small,sharply demarcated, asymptomatic, often multiplered nodules.o Eventually most such tumors become large fleshymasses of pale gray-white soft tissue.o The margins blend with surrounding structures.o Central softening and areas of necrosis andhemorrhage are frequent.
Microscope :o All degrees of differentiation may be found.o From those that are vascular lined with plump,anaplastic endothelial cells.o To tumors that are quite undifferentiated,produce no definite blood vessels, markedly atypical,and have solid spindle cell appearance.o Endothelial cell derivation is demonstrated byimmunostaining for CD31, CD34, or vWF .
Angiosarcoma on ChestHigh-grade angiosarcoma. The tumor demonstrates diffusecytologic atypia and a combination of irregular vasoformative andsolid growth.High-grade angiosarcoma ,At high power, the widespreadnuclear hyperchromasia andpleomorphism are easily seen, asare the numerous mitotic figures.
Hemangiopericytoma: Neoplasms with a grossly fleshy or spongyconsistency ; and a thin-walled branching("staghorn") vascular pattern microscopically. Derived from pericytes (the cells normally arrangedalong capillaries and venules). Arise as slowly growing masses in retroperitoneumor lower extremities (especially thigh) ofmiddle aged women. Reaching 5 to 15 cm in maximum diameter. Two-thirds have a benign course, but one-thirdare malignant. Presence of necrosis, high mitotic rate, andnuclear pleomorphism, especially in a large tumor,is associated with aggressive behavior.