Path 3

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Pathology

Lecture 18

prof. dr hab. n. med. Andrzej Marszaek

soft tissue tumors bone tumors

SOFT TISSUE TUMORS (SARCOMAS)

Soft tissues are of mesenchmal origin, in this group we include tumors of: muscles, tendons, fat, fibrous tissue, synovial tissue, vessels, and nerves.

Localization: 60% in the extremities,

(lower : upper extremities = 3:1); 30% in the trunk

(40% of them in the retroperitoneum) 10% in the head and neck


Incidence: 0.7% of all cancers in the general population

(but 6.5% of all malignancies in children)

2 cases/100,000 population/year (in USA in 1996 6400, and in 2004 8680 new cases).


Epidemiology: usually de novo in rare cases as a malignant transformation of a

benign lesions except: malignant peripheral nerve sheath

tumors (neurofibrosarcoma, malignant schwannoma) can arise from neurofibromas in patients with neurofibromatosis


Etiology: factors have been implicated in the patho-genesis of soft tissue sarcomas A. Environmental factors trauma/previous injury (rarely) can arise in scar tissue (prior operation, burn,

fracture, or foreign body implantation, with latency from 2 to 50 years)

chemical carcinogens (polycyclic hydrocarbons, asbestos, phenoxy herbicides, Agent Orange, and dioxin)

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B. latrogenic factors in cancer patients who are treated with radiation

and survive at least 5 years (latency even 10 years)

C. Viruses HIV type 1 Kaposi's sarcoma (KS) human herpes virus (HHV8) AIDS-associated

KS, classic KS, and KS in HIV-negative homosexual men (in all aforementioned cases could be herpesvirus-like DNA+)


D. Immunologic factors congenital or acquired immunodefi-ciency E. Genetic factors Li-Fraurneni syndrome (familial cancer syn-drome, with germ-line abnormalities of the tumor suppressor gene p53) increased incidence of soft tissue sarcomas and other malignancies (breast cancer, osteosarcoma, brain tumors, leukemia, and adrenal carcinoma)


E. Genetic factors neurofibromatosis 1 (NF-1, peripheral form, von

Recklinghausen's disease) with multiple neurofibromas and cafe au lait spots.

germ-line mutation of the Rb-1 locus inherited retinoblastoma is associated with the development of osteosarcorna

familial predisposition for desmoid tumors, lipomas, leiomyomas, neuroblastomas, and paragangliornas


F. Other factors - IGF- 2 is produced by some sar-comas (autocrine growth factor and a motility factor) - antibodies to IGF-1 receptors block the stimulation of growth by IGF-2 in vitro but do not affect IGF-2-induced motility.


CLASSIFICATION large and heterogeneous group of neoplasms approximately 20 different types of sar-comas are recognized


CLASSIFICATION rhabdomyosarcoma skeletal muscle fibers

with cross-striations leiomyosarcomas interlacing fascicles of

spindle cells representing smooth muscle fea-tures

liposarcomas adipocytes angiosarcomas rich network of blood

vessels unclassified sarcomas

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CLASSIFICATION but morphologic, immunohistochemical,

and experimental data suggest that most (if not all) arise from primitive multipotential mesenchymal cells, which in the course of neoplastic transformation undergo differentiation along one or more lines


CLINICAL BEHAVIOUR for treatment most soft tissue sarcomas can be lumped together the most common presentation is an asymptom-atic mass but may cause: compression, traction, or entrapment of nerves or muscles sarcomas tend to metastasize through the blood rather than the lymphatic system (5% of cases)


diagnosis by: HE IHC cytogenetics molecular studies ultrastructure


IHC (basic): cytokeratins vimentin smooth muscle actin desmin S-100 CD 31 CD 34


cytogenetic markers: t(2;13) Alveolar rhabdomyosarcoma t(11;22) Ewings sarcoma/PNET t(11;22) Desmoplastic small round cell tumor t(12;16) Myxoid liposarcoma t(9;22) Myxoid chondrosarcoma t(12;22) Clear cell sarcoma t(X;18) Synovial sarcoma

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Lipoma Angiolipoma

liposarcoma

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Leiomyoma there are several types of leiomyomas

cutaneous leiomyomas located in the dermis genital leiomyomas are solitary tumors that arise from smooth muscle

bundles located in the superficial subcutaneous tissue of genital areas (nipple, areola, axilla, scrotum, penis, vulvar labia, and anal skin)

vascular leiomyomas (angioleiomyomas) arise from the smooth muscle of blood vessels.

more fre-quent in females usually located in the soft tissues of the lower limbs (is an example of

spontaneously painful nodule together with: traumatic neuroma, glomus tumor, eccrine spiradenoma, and angiolipoma)

grossly: are yellow or yellowish pink, sharply circumscribed, and fairly firm microscopically: made up of intersecting fasci-cles of smooth muscle

cells encircling vascular lumina lined by normal endothelial cells

Leiomyosarcoma relatively rare tumor typically occurs in adults and the elderly increasing frequency in immunosuppressed patients most soft tissue leiomyosarcomas are located in the extremities

grossly: well circum-scribed as the leiomyomas but are larger and softer and fresh necrosis, hemorrhage, and cystic degeneration; microscopically: fascicular pattern, with the tumor bundles intersecting each other at wide angles;

Rhabdomyosarcoma three major categories of rhabdomyosarcoma: pleomorphic, embryonal, and alveolar pleomorphic rhabdomyosarcoma

the least common of the three categories. located in an extremity (thigh) almost exclusively in adults

microscopically: very pleomorphic, numerous tumor giant cells evidence of skeletal muscle differentiation (cross striations) or demonstration of specific ultrastructural or immunohistochemical markers

treatment before 1960 100% death (5yrs) now: surgery + chemo- + RTG 5-zrs survival:

botryoid embryonal RMS 95% classic embryonal RMS 66% alveolar RMS 54%

in 20% metastases: lungs, bones, lzmph nodes

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Embryonal Rhabdomyosarcoma Embryonal rhabdomyosarcoma arises from unsegmented and

undifferentiated mesoderm and is common in the head and neck region (particularly the orbit, nasopharynx, middle ear, and oral cavity), retroperitoneum, bile ducts, and urogenital tract

large majority occur in children between the ages of 3 and 12 years, but they can also be seen in younger patients and in adults

grossly: tumor is poorly circumscribed, white, and soft; when growing beneath a

mucosal membrane, such as the vagina, uri-nary bladder, or nasal cavity, it frequently forms large polypoid masses resembling a bunch of grapeshence the name sarcoma botryoides the appearance is quite similar to that of an aller-gic nasal polyp, and, as such, is deceptively benign

microscopically: small and spindle shaped cells;

highly characteristic feature of the polypoid ("botryoid") tumors is the presence of a dense zone of undifferentiated tumor cells immediately beneath the epithelium, Cross striations may or may not be present

Alveolar Rhabdomyosarcoma

Alveolar rhabdomyosarcoma may be related to the embryonal form and it is said to occasionally coexist with it

it differs from the embryonal subtype in several ways

it predominates in an older age group (10 to 25 years) occurs more frequently in the extremities: - the most common locations being forearms, arms, and perirectal and

perineal regions

microscopically: small, round, or oval tumor cells are seen separated in nests by connective tissue septa

Pleomorphic Rhabdomyosarcoma

v w miniach u osb starszych

v znaczny pleomorfizm

v nieregularnie uoone komrki

v wielojdrowe olbrzymie komrki

FIBROUS TUMORS

BENIGN Nodular Fasciitis

Palmar fibromatosis Abdominal fibromatosis (desmoid tumor)

MALIGNANT

Fibrosarcoma

Fibrosarcoma common tumor of adults (BUT can occur in any age group) can arise from superficial and deep connective tissues such as: fascia, tendon, periosteum, and scar; grow slowly or rapidly; and often appear well circum-scribed usually are soft and cellular and may contain areas of necrosis and hemorrhage microscopically:

the well-differentiated tumors are easily recognized as fibroblastic cells are arranged in fascicles that intersect each other at acute angles resulting in a herringbone appearance individual cells resemble fibroblasts

capable of distant metastases (50%) survival rate in a recent large series was 41% at 5 years and 29% at 10 years

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