Path Quiz Case 36:
Images and history:
Kaposi's sarcoma (KS) is a low-grade, spindle-cell neoplasm
first described by Moritz Kaposi, in 1872.
Visit:
AIDS: Cutaneous
lesion associated with AIDS ;
AIDS related malignant tumours.
Although the exact pathogenesis of KS is not known, infection
with HHV-8 / KS-associated herpes virus , combined with other genetic
and environmental factors, has been strongly implicated as the cause of
this disease.
HHV-8 has been detected in KS cells of patients in all 4
epidemiologic groups, suggesting that the virus is a common pathogenetic
factor for all KS types.
(HHV-8 has also been
implicated in the pathogenesis of multicentric Castleman's disease and
primary effusion lymphomas.)
HHV-8 infects CD19(+) B
cells as well as T cells, monocytes, endothelial- derived spindle cells
and CD34 (+) cells in the peripheral blood of patients with Kaposi's
sarcoma. There are three subtypes of HHV-8 (A, B and C). Type C
infection is usually not associated with extracutaneous disease.
The tumour begins
as a reactive proliferation but behaves as a multifocal neoplasm in
advanced stage.
The spindle cells in
Kaposi's Sarcoma are thought to be the proliferating component while the
endothelial cell population is thought to undergo a reactive hyperplasia.
Some authors have suggested that the spindle cell elements show
endothelial differentiation.
Chronic stimulation of endothelial cells (possibly by viral infection) can
produce differentiation to spindle shaped cells.
Kaposi's
sarcoma: immunohistologic evidence for an endothelial origin. Arch
Pathol Lab Med. 1981;105(5):274-5.
;
Histogenesis of Kaposi's sarcoma and angiosarcoma of
the face and the scalp.J
Invest Dermatol.
1989;93(2 Suppl):119S-124S.
;
Histogenesis
of Kaposi's sarcoma associated with AIDS: a histologic,
immunohistochemical and enzyme histochemical study.Pathol Res Pract.
1987 Oct;182(5):658-68.
;
Histogenesis
of Kaposi's sarcoma in patients with and without acquired immune
deficiency syndrome (AIDS).J Clin Pathol. 1986
Jul;39(7):742-9.
Origin of spindle-shaped cells in
Kaposi sarcoma.Lymphology.
1994 Mar;27(1):41-4.
Recent studies have
indicated that the spindle cells are derived from the lymphatic
endothelium.
The
Histogenesis of Kaposi's sarcoma (KS) cell: immunomorphological comparison
with endothelial cells of normal human skin, lymphangioma and hemangioma.
Arch Dermatol Res 1994;286:212 ;
Expression of D2-40 in lymphatic endothelium of
normal tissues and in vascular tumours.
Histopathology.
2005 Apr;46(4):396-402.
;
Monoclonal antibody D2-40, a new
marker of lymphatic endothelium, reacts with Kaposi's sarcoma and a subset
of angiosarcomas.
Mod Pathol.
2002;15(4):434-40
Kaposi's sarcoma can be
subdivided into 4 epidemiologic groups:
| 1. Classic variant:
Usually
affects elderly men of Eastern
European and Mediterranean origin ; Usually present In fifth and
seventh decade ; More common in men than in women, with a ratio15 to 1
;
Presents as multiple firm, purple-blue or reddish-brown plaques
and nodules ;
Typically appear initially on
the hands and feet ; Progress
up the arms and legs over a period of years or decades;
Involve the
viscera or mucosa about 10 percent of patients ; Untreated
lesions evolve from flat discolorations
or patches to plaques and then to raised nodules that become
confluent ; Histologic features - spindle-shaped tumour cells surrounding hyperemic vascular slits,
extravasated erythrocytes, hemosiderin,
and fibrosis ;
Increased risk of lymphoma ; Homosexual men may be at
increased risk for classic type KS. |
|
2. Epidemic (HIV- associated):
In 1981, Friedman-Kien et
al. described Kaposi's sarcoma involving lymph nodes, viscera, and
mucosa as well as skin in young homosexual men ; This aggressive and
frequently fatal epidemic
variant of KS affected homosexual men with AIDS, 20
times as frequently as it did male patients with hemophilia and
AIDS who had similar degrees of immunosuppression ; This variant is also
observed in intravenous drug users ; Epidemic variant of KS has an
extensive distribution and rapid progression. |
| 3. Immunosuppression
associated: Present in
organ-transplant
recipients and patients who are receiving corticosteroid or immunosuppressive
therapy for a variety of medical conditions ;
This type of KS
tends to be aggressive, involving lymph nodes, mucosa, and
visceral organs in about half of patients, sometimes in the
absence of skin lesions ; The presence of concurrent lymphoma,
tuberculosis, or transfusion-related HIV infection makes it
difficult to diagnose KS accurately. |
| 4. African (endemic) :
In the 1950s, KS was recognized as being common
in portions of Africa. It was reported in
Uganda and Zambia.
In eastern and southern Africa, KS makes up 25 to 50 percent of
soft-tissue sarcomas in children.
Subtypes:
Lymphadenopathic type
: Usually noted in children. The patients have a poor
prognosis.
Nodular disease: Resembles
classic type.
Aggressive atypical variant :
Characterized by generalized, infiltrative skin lesion in adults. This
variant responded poorly to conventional treatment. |
Histopathological features:
Image1 ;
Image2 ;
Image3 ;
Image4
Multiple
clinicopathologic forms of KS, which are not mutually exclusive and can
have overlapping features, have been described.
Patch ; plaque ; nodular ; lymphadenopathic
; infiltrative ; florid ; telangiectatic ; ecchymotic ; keloidal
; angiomatous ; inflammatory ; anaplastic ; lymphangiomatous ; and generalized lymphedema
.
Patch Stage:
Flat lesion characterized by proliferation
of numerous jagged vascular spaces in the dermis ; The vascular spaces are parallel to the
epidermis ; The slit like vessels are present around preexisting blood vessel , skin adnexa and between collagen fibres. ( 'Promontory sign' )
; Vessels are lined by plump, mildly atypical endothelial cells ; Perivascular lymphocytes and plasma cells
; Extravasated red blood cells
and hemosiderin may be present ; The features resemble granulation tissue.
Plaque Stage:
Spindle cells are more prominent than those in the 'patch stage' ;
Dermal proliferation of the spindle cells together with
poorly defined slit-like blood vessels ; Involves the reticular dermis and even the subcutis ;
Hemosiderin deposition is prominent ;
Eosinophilic globules are present .
Nodular Stage:
Well defined lesion characterized by prominent interlacing bundles of
spindle cells around slit like blood vessels and extravasation of red
blood cells ; These features are more prominent than those in the 'plaque
stage' ; Dilated thin walled vessels are present at the periphery ;
Mitotic figures are present ;
Eosinophilic hyaline globules are present (intra and extra cellular)
; These are PAS- positive and stain bright red with Mallory's trichrome.
Lymphangioma-like Kaposi's sarcoma
(LLKS):
Clinically, the lesions have a bulla like appearance.
Histologically, the tumour is characterized by permeation of dermal
collagen by irregular anastomosing vascular channels lined by a flattened
endothelium.
The
biopsy specimens also reveal areas with characteristic light microscopic
features of KS. All tumour cells, show a strong and diffuse
reactivity for anti-HHV-8 LNA-1 and anti-CD34.
Lymphangioma-like
Kaposi sarcoma.
J
Cutan Pathol. 2005;32(4):286-92.
;
Lymphangioma-like Kaposi's sarcoma: etiology and
literature review. J
Am Acad Dermatol.
2000;43(1 Pt 1):123-7. ;
Benign lymphangioendothelioma
(acquired progressive lymphangioma): a lesion not to be confused with
well-differentiated angiosarcoma and patch stage Kaposi's sarcoma:
clinicopathologic analysis of a series.
Am J Surg Pathol.
2000;24(8):1047-57.
;
Lymphangioma-like variant of
Kaposi's sarcoma: clinicopathologic study of seven cases with review
of the literature.
Am J Dermatopathol.
1997;19(1):16-22.
Anaplastic variant of Kaposi's Sarcoma:
Cases have been reported in Africa.
Characterized
by :- Greater cellularity ; Nuclear pleomorphism ; Frequent
mitotic activity.
Kaposi's sarcoma: histopathological study of 159
cases from Malawi.
J Clin Pathol.
1977;30(8):687-95.
;
Kaposi's
sarcoma in Uganda: a clinico-pathological study.Int
J Cancer.
1971;8(1):122-35.
Immunohistochemistry:
Kaposi's sarcoma is positive for both CD31 and CD34. Some cases are
positive for factor VIII-related antigen. Human herpes virus type- 8 can be detected by PCR
in paraffin-embedded tissue. Recently, a monoclonal antibody to
human herpes virus 8 latent nuclear antigen-1 has become commercially
available for immunohistochemical analysis. Kaposi sarcoma shows
strong, diffuse, nuclear staining for human herpes virus 8 latent
nuclear antigen-1.
CD31 immunoreactivity in
mesenchymal neoplasms of the skin and subcutis: report of 145 cases
and review of putative immunohistologic markers of endothelial
differentiation.J
Cutan Pathol. 1995;22(3):215-22.
Endothelial cell markers CD31,
CD34, and BNH9 antibody to H- and Y-antigens--evaluation of their
specificity and sensitivity in the diagnosis of vascular tumors and
comparison with von Willebrand factor.Mod
Pathol. 1994;7(1):82-90.
Immunohistochemical detection of human herpes virus-8 latent nuclear
antigen-1 is useful in the diagnosis of Kaposi sarcoma.Mod
Pathol. 2004;17(4):456-60.
Early vascular lesions
should be differentiated from telangiectasia, pigmented purpuric
dermatosis ,acroangiodermatitis
(Acro-angiodermatitis. A
simulant of Kaposi's sarcoma.
Am
J Dermatopathol. 1987; 9 (2):85-9.)
and low grade angiosarcoma. Vessels in KS are more irregular. An
inflammatory infiltrate which includes plasma cells is present in
early lesions of KS.
Regressed KS lesions
following therapy may be misdiagnosed clinically and histologically as pigmented purpuric dermatitis
if the pathologist is not aware of the previous history.
The histologic differential diagnoses of KS include
other vascular tumours, such as
spindle cell hemangioendothelioma , kaposiform hemangioendothelioma, and angiosarcoma.
Spindle cell hemangioendothelioma:
In addition
to a solid spindle cell component resembling KS, there are dilated and cavernous vascular
spaces.
Kaposiform hemangioendothelioma is a pediatric tumour composed of
multiple lobules, each of which resemble either KS or capillary hemangioma,
and is often associated with Kasabach-Merritt syndrome. HHV-8 has not been
associated with kaposiform hemangioendothelioma.
Angiosarcoma is
characterized by a
complex anastomosing pattern and marked nuclear atypia. The presence of
hyaline bodies and deposits of haemosiderin indicate Kaposi's sarcoma.
The
spindle cell predominant type KS may be confused with leiomyoma,
leiomyosarcoma, or
fibrosarcoma. The presence of hyaline bodies and the
formation of vascular channels between spindle cells point to a diagnosis
of Kaposi's sarcoma.
Lymphangioma-like Kaposi's sarcoma characterized by permeation of dermal
collagen by labyrinthine vascular channels lined by a flattened
endothelium, must be differentiated from
spindle cell hemangioendothelioma
,
low-grade angiosarcoma,
targetoid hemosiderotic hemangioma
(Target-like hemosiderotic
hemangioma. Further differential diagnosis of Kaposi sarcoma.Hautarzt.
1994 Jan;45(1):34-7.)
, and benign
lymphangioendothelioma .
Other
histologic simulators of Kaposi's sarcoma are
reactive angioendotheliomatosis ;
bacillary angiomatosis ;
microvenular hemangioma ;
hobnail hemangioma
;
pyogenic granuloma ;
aneurysmal fibrous histiocytoma ;
arteriovenous
hemangioma ;
verrucous hemangioma; nonspecific
vascular proliferation;
angiomatoid malignant fibrous histiocytoma
;
dermatofibrosarcoma protuberans; vascular
transformation of lymph node ; pilar leiomyoma ; stasis dermatitis ;
spindled melanoma.
|
Abstracts:
Latency-associated nuclear
antigen expression and human herpesvirus-8 polymerase chain reaction
in the evaluation of Kaposi sarcoma and other vascular tumors in
HIV-positive patients.Mod
Pathol. 2005;18(4):463-8.
Aggressive behavior of
classical Kaposi's sarcoma and coexistence with angiosarcoma.J
Gerontol A Biol Sci Med Sci.
2005;60(4):520-3.
Occurrence of tubuloreticular
structures and intracisternal paracrystalline inclusions in
endothelial cells of tissue from different epidemiological types of
Kaposi's sarcoma.Ultrastruct
Pathol. 2005
;29(2):85-93.
Conjunctival Kaposi sarcoma as
the initial presentation of human immunodeficiency virus infection.Ophthal
Plast Reconstr Surg.
2005;21(4):314-5.
C-Kit (CD117) expression in AIDS-related, classic,
and African endemic Kaposi sarcoma.Appl
Immunohistochem Mol Morphol. 2005;13(2):162-6.
Histological characterization of regression in
acquired immunodeficiency syndrome-related Kaposi's sarcoma.J
Cutan Pathol. 2004 ;31(1):26-34.
Immunostaining for human
herpesvirus 8 latent nuclear antigen-1 helps distinguish Kaposi
sarcoma from its mimickers.Am
J Clin Pathol.
2004;121(3):335-42.
Misleading Kaposi's sarcoma:
usefulness of anti HHV-8 immunostaining.
Ann Pathol.
2003 ;23(4):345-8
Human herpesvirus-8 latent
nuclear antigen-1 expression in endemic Kaposi sarcoma: an
immunohistochemical study of 16 cases.
Am J Surg Pathol.
2003;27 (12):1546-50.
HHV-8 DNA sequences in the peripheral blood and skin lesions of an
HIV-negative patient with multiple eruptive dermatofibromas:
implications for the detection of HHV-8 as a diagnostic marker for
Kaposi's sarcoma.Dermatology.
2003;206(3):217-21.
Benign
vascular proliferations in irradiated skin.Am
J Surg Pathol.2002;26(3):328-37.
Unidentified bacterial
microorganisms entrapped within blood capillary spaces of tissue from
different epidemiological types of Kaposi's sarcoma.
Ultrastruct Pathol.
2001;25(2):129-35.
Biology of Kaposi's sarcoma.Eur
J Cancer. 2001;37(10):1251-69.
Kaposi sarcoma of
major salivary gland origin: A clinicopathologic series of six cases. Cancer.
2000;88(1):15-23.
The epidemiologic, pathologic,
and clinical features of AIDS-associated pulmonary Kaposi's sarcoma.Chest.
2000;117(4):1128-45.
Proliferation and apoptosis in
the evolution of endemic and acquired immuno-deficiency
syndrome-related Kaposi's sarcoma.
Med Oncol.
2000;17(4):325-32.
Update on the pathogenesis and
treatment of Kaposi sarcoma.Curr
Opin Oncol. 2000
;12(2):174-80.
Vascular endothelial growth
factor receptor-3 (VEGFR-3): a marker of vascular tumors with presumed
lymphatic differentiation, including Kaposi's sarcoma, kaposiform and
Dabska-type hemangio- endotheliomas, and a subset of angiosarcomas.
Mod Pathol. 2000;13(2):180-5.
Diagnostic
implication of Kaposi's sarcoma-associated herpesvirus with special
reference to the distinction between spindle cell hemangio-endothelioma
and Kaposi's sarcoma. Arch
Pathol Lab Med. 1998;122(1):72-6.
Kaposi's sarcoma of the oral
cavity in a non-AIDS patient: case report and review of the
literature. Head
Neck.1995;17(1):64-8.
Classic and iatrogenic
Kaposi's sarcoma. Histopathological patterns as related to clinical
course. Am
J Dermato pathol.1993;15(6):523-7.
Immunohistochemical
detection of Bcl-2 in AIDS-associated and classical Kaposi's sarcoma.
Am
J Pathol. 1996;148(4):1055-63.
Herpesvirus-like DNA sequences
and Kaposi's sarcoma: relationship with epidemiology, clinical
spectrum, and histologic features.Cancer.
1996;77(10):2132-6.
A role for a new herpes virus
(KSHV) in different forms of Kaposi's sarcoma.Nat
Med. 1995
;1(7):707-8.
Hyaline globules in Kaposi's
sarcoma: a light microscopic and immuno histochemical study.
Mod Pathol.1991
;4(2):187-90
Molecular mechanisms in the
pathogenesis of AIDS-associated Kaposi's sarcoma.
Adv Exp Med Biol.
1991;303:27-38.
Endemic and atypical Kaposi's
sarcoma in Africa--histopathological aspects.
Clin Exp Dermatol.
1990;15(4):253-9.
Histology of early lesions of AIDS-associated Kaposi's
sarcoma. ModPathol. 1990; 3(1):64-70.
The spindle-shaped cells in
cutaneous Kaposi's sarcoma. Histologic simulators include factor XIIIa
dermal dendrocytes. Am
J Pathol. 1989;135(5):793-800.
Clinical and histo-
pathological aspects of Kaposi's sarcoma in Africa: relationship with
HIV serology.
Ann Inst Pasteur Virol.
1988 ;139(2) :197-203.
Angioproliferative changes in
clinically noninvolved, perilesional skin in AIDS-associated Kaposi's
sarcoma.
Dermatologica.
1987;175(6):270-9.
Kaposi's sarcoma in AIDS.
Multicentric angio- neoplasia in early skin lesions.
Am J Dermato pathol.1987;9(5) :388-98
Changing patterns of Kaposi's
sarcoma in N.E. Zaire.Trans
R Soc Trop Med Hyg.
1986;80(6):965-6.
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