Pathology

soft tissue tumors

bone tumors

Lecture 18
prof. dr hab. n. med. Andrzej Marszaek

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

SOFT TISSUE TUMORS (SARCOMAS)

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

SOFT TISSUE TUMORS (SARCOMAS)

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).

SOFT TISSUE TUMORS (SARCOMAS)

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)

SOFT TISSUE TUMORS (SARCOMAS)

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+)

SOFT TISSUE TUMORS (SARCOMAS)

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

SOFT TISSUE TUMORS (SARCOMAS)

CLASSIFICATION
large and heterogeneous group of
neoplasms
approximately 20 different types of sarcomas are recognized

SOFT TISSUE TUMORS (SARCOMAS)

D. Immunologic factors
congenital or acquired immunodefi-ciency
E. Genetic factors
Li-Fraurneni syndrome (familial cancer syndrome, 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)

SOFT TISSUE TUMORS (SARCOMAS)

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.

SOFT TISSUE TUMORS (SARCOMAS)

CLASSIFICATION
rhabdomyosarcoma skeletal muscle fibers
with cross-striations
leiomyosarcomas interlacing fascicles of
spindle cells representing smooth muscle features
liposarcomas adipocytes
angiosarcomas rich network of blood
vessels
unclassified sarcomas

SOFT TISSUE TUMORS (SARCOMAS)

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

SOFT TISSUE TUMORS (SARCOMAS)

SOFT TISSUE TUMORS (SARCOMAS)

CLINICAL BEHAVIOUR

diagnosis by:

for treatment most soft tissue sarcomas can be

lumped together
the most common presentation is an asymptomatic 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)

HE
IHC
cytogenetics
molecular studies
ultrastructure

SOFT TISSUE TUMORS (SARCOMAS)

SOFT TISSUE TUMORS (SARCOMAS)

IHC (basic):

cytogenetic markers:

cytokeratins
vimentin
smooth muscle actin
desmin
S-100
CD 31
CD 34

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

Lipoma

Angiolipoma

liposarcoma

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

Rhabdomyosarcoma
three major categories of rhabdomyosarcoma:

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;

treatment

pleomorphic, embryonal, and alveolar

before 1960 100% death (5yrs)

pleomorphic rhabdomyosarcoma

now:
surgery + chemo- + RTG 5-zrs survival:
botryoid embryonal RMS 95%
classic embryonal RMS 66%
alveolar RMS 54%

the least common of the three categories.

located in an extremity (thigh)
almost exclusively in adults
microscopically:
very pleomorphic,

in 20% metastases: lungs, bones, lzmph nodes

numerous tumor giant cells

evidence of skeletal muscle differentiation (cross striations)
or demonstration of specific ultrastructural or immunohistochemical markers

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 grapes
hence the name sarcoma botryoides the appearance is quite similar to
that of an aller-gic nasal polyp, and, as such, is deceptively benign

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

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

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