Dermatologicmanifestations of Internalcancer: Bruce H. Thiers, M.D
Dermatologicmanifestations of Internalcancer: Bruce H. Thiers, M.D
Dermatologicmanifestations of Internalcancer: Bruce H. Thiers, M.D
Of InternalCancer
132 CA-ACANCER
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FORCLINICIANS
is most often reported in later stages of the
disease, more advanced techniques have r
demonstrated that internal involvement may
occur much earlier than has previously been
recognized .“@
The three-stage sequence of mycosis
fungoides is not apparent in all patients.
Occasionally, the disease begins with the
plaque stage; in the d'embléeform, tumors
are the initial manifestation. Sézarysyn
drome, the association of large numbers of
circulating atypical lymphocytes with an
/11@
erythroderma histologically similar to my
Fig. 4. Alopecia mucinosa.
cosis fungoides, may occur de novo or as
a late manifestation of mycosis fungoides.
Woringer-Kolopp disease probably repre
Histiocytosis X
sents a particularly epidermotropic form of
mycosis fungoides. Affected patients usu The three clinical patterns of histiocytosis
ally have a few well-circumscribed irreg X—Letterer-Siwe disease, Hand-SchUller
ular plaques that enlarge slowly or not at Christian disease, and eosinophilic gran
all; histologic examination shows massive uloma of bone—are all variations of a sin
epidermal invasion by tumor cells. Al gle pathologic process: a disseminated,
though internal involvement may never oc progressive, and invasive proliferation of
cur, some patients have shown more atypical but well-differentiated histiocytes,
progressive cutaneous and systemic dis which may, in fact, represent activated
ease. It is possible that only this second Langerhans cells.― The neoplastic nature
group of patients should be considered to of histiocytosis X has not been firmly es
have a variant of mycosis fungoides. tablished, and recent studies suggest that
Alopecia mucinosa may occur in as it may, at least at its onset, represent a state
sociation with mycosis fungoides or, es of altered immunity.'2'5 Thus, like my
pecially in children and adolescents, as an cosis fungoides, histiocytosis X may be an
isolated, self-limited condition. The le example of “¿immunologiconcogenesis,―
sions, which are typically located on the the evolution of an inflammatory process
face, neck, scalp, and proximal upper ex into a malignant disease.
tremities, consist of groups of follicular Letterer-Siwe disease occurs almost
papules or boggy infiltrated plaques as exclusively in children three years of age
sociated with hair loss (Fig. 4). Histologic or younger. Most patients have skin le
examination shows accumulation of acid sions, which are either localized to or ac
mucopolysaccharide in the outer root sheath centuated in the seborrheic areas, including
and sebaceous glands. Depending on the the scalp, behind the ears, and in the ax
clinical setting, the inflammatory infiltrate illary and inguinal folds (Fig. 5). Cuta
may or may not show evidence of mycosis neous findings consist of an eruption similar
fungoides, which can either precede or ac to infantile seborrheic dermatitis; papular
company the disorder. and nodular lesions may also be found. The
Patients with evidence of infection with dermatosis is often purpuric, and papules
type I human T-cell leukemia/lymphoma in skin folds may ulcerate. Involvement of
virus (HTLV- 1) may present with hyper the external auditory canal may simulate
calcemia, lytic bone lesions, and an illness external otitis. Intraoral involvement may
not unlike cutaneous T-ceII lymphoma, al cause ulceration of the buccal mucosa and
though skin lesions may be absent.9 An gums.
association of typical cutaneous T-cell Letterer-Siwe disease is usually an
lymphoma with HTLV infection is un acute, fulminant, ultimately fatal disorder
likely. associated with fever, anemia, thrombo
course. Rarely, patients with systemic in fibroblasts and endothelial cells.'4 Kaposi's
volvement have a progressive downhill sarcoma may occur de novo, especially in
lymphoma-like course terminating in leu elderly persons, or may be seen in asso
kemia. ciation with states of altered immunity, such
A variety of cutaneous lesions may be as after renal transplantation in patients with
associated with mast cell disease. Solitary lymphomas or in patients with acquired
mastocytomas are usually seen in children. immune deficiency syndrome (AIDS). Race
Multiple, small, brown, hyperpigmented
macules or slightly elevated papules are the
most common skin manifestations and can Although idiopathic
be observed at any age (Fig. 6). In chil Kaposi's sarcoma
dren, these often clear during the late teen is usually a slowly progressive
age years. With later onset, lesions tend to
persist unchanged or may become more
condition that may span
numerous and virtually confluent. The hy 10 or more years, in
perpigmented macules of telangiectasia immunosuppressed patients
macularis eruptiva perstans (seen mostly the disease often
in adults) and the erythroderma of diffuse follows a more
mastocytosis (seen in all age groups) are
rare.
accelerated course.
Systemic lesions occur more fre
quently in adults, can be detected in about and geography may affect the incidence of
10 percent of affected individuals, and may Kaposi's sarcoma.
be associated with any type of skin lesion. The disorder usually starts as circum
scribed red-brown or purple macules, pa
pules, or nodules on the feet or lower legs
Kaposi's Sarcoma
(Fig. 7). Lesions may become increasingly
Like the disorders already discussed, Ka infiltrated and coalesce to involve large
posi's sarcoma is of multifocal origin. As areas of skin. Edema and lymphedema may
with mycosis fungoides and histiocytosis develop. Extracutaneous spread occurs
X, Kaposi's sarcoma may be a reactive most often to the gastrointestinal tract,
process that undergoes malignant transfor where bleeding is a frequent complication.
mation, rather than a frank neoplasm from Metastases to the respiratory tract may also
its inception. It appears to represent a pro occur, and other sites may be involved as
liferation of lymphoreticular and pluripo well. Idiopathic Kaposi's sarcoma is gen
tential vascular cells that differentiate into erally a slowly progressive condition that
Metastatic Carcinoma
The incidence of involvement of skin in
Fig.10. Adenocarcinoma of stomach met metastatic disease is relatively low com
astatic to umbilicus (Sister Joseph nodule). pared with other organs and probably av
erages about five to 10 percent. Although
any cancer can spread to skin, most cu
taneous metastases are of carcinomatous
origin. The lung is the most frequent source
of cutaneous metastases in the male; the
breast is the usual source in females. In
may span a decade or more. In immuno both sexes, metastases are most often found
suppressed individuals, however, the dis on the skin of the abdomen and anterior
ease often follows an accelerated course; chest; the head and neck are also favored
the initial lesions may then occur anywhere sites, especially in men.
and frequently involve mucosal surfaces The location of the metastatic tumor
(Fig. 8).'@ Conversely, when immuno is often a clue to the site of the primary
suppressive therapy is discontinued, the lesion. Metastases to the head, neck, and
sarcomatous lesions may spontaneously anterior chest often originate in lung tu
regress. 6 mors in men (Fig. 9) and breast cancers
in women. Metastases to the upper abdom
Cutaneous Metastases of Internal inal wall generally spread from gastroin
testinal lesions; the lower abdominal wall
Neoplasms
and external genitalia are the favored site
Cutaneous metastases usually occur via one for genitourinary cancers. Carcinoma met
of two routes: Tumor cells may either be astatic to the umbilicus (Sister Joseph nod
transported to the skin from distant sites ule) is usually a sign of an underlying
via the blood vessels or lymphatics, or they adenocarcinoma of the stomach (Fig. 10).
may reach the skin via extension from a Melanomas usually metastasize to the ex
VOL.36,NO.3 MAY/JUNE
1986 137
affects the face and extremities, and gran
ulocytic leukemia which preferentially in
filtrates the skin of the trunk. Although
leukemia cutis occurs most often in chronic
leukemia, oral involvement, as evidenced
by gingival infiltration and hyperplasia, is
a feature of both the acute and chronic
stages of the disease, especially the mono
cytic variety.
Chloroma is a peculiar tumor of my
elogenous origin and is the sole patho
gnomonic lesion of leukemia. Its charac
teristic green color on exposure to light is
Fig. 14. Paget's disease of breast. probably due to the presence of the enzyme
myeloperoxidase in the cells of the tumor,
which consist primarily of malignant my
eloblasts and myelocytes. Chloroma usu
volvement may precede evidence of more ally affects the periorbital and cranial bones,
generalized disease; rarely, the skin may and is seen most often in children and young
be the primary site of involvement in pa adults with acute granulocytic leukemia.
tients with B-cell lymphomas (cutaneous The lesion, which can occur anytime dur
B-cell lymphoma).'7 In Hodgkin's disease, ing the course of the disease or even be its
involvement of skin may be a consequence presenting sign, carries poor prognostic
of retrograde flow from involved lymph implications.
nodes rather than active cutaneous inva
sion. Histologic examination of specific
skin lesions, while useful for establishing Tumors Arising Within or
the diagnosis of lymphoma, rarely allows Below the Skin
for more precise classification. Paget's disease is the prototypic malignant
The types and morphology of the spe disease that begins below the skin and ex
cific and nonspecific lesions of leukemia tends to the cutaneous surface. While most
often noted on the female breast, the con
dition may also occur in the anogenital re
The cutaneous gion of both sexes and rarely in the axilla
manifestations of internal (extramammary Paget's disease).
cancer can develop Paget's disease of the breast begins as
a unilateral, occasionally pruritic, ecze
either before or after the matous weeping eruption of the nipple and
presence of an areola with a fairly sharp, sometimes ir
underlying tumor has regular border (Fig. 14). Topical treatment
been established. is ineffective. Examination of a biopsy
specimen shows numerous large, round
cells with clear cytoplasms (Paget cells)
are similar to those encountered in the lym infiltrating the epidermis. Although an un
phomas. Specific skin lesions are some derlying ductal adenocarcinoma is almost
what more common in monocytic than in always found, the traditional “¿epidermo
lymphocytic or granulocytic leukemia; tropic―theory of histogenesis has recently
since the incidence of lymphocytic leu been challenged.―'
kemia is relatively high, however, its der Extramammary Paget's disease occurs
matologic manifestations are most often more often in women than in men, usually
seen. There is no specific site of predilec after age 50. Lesions can occur anywhere
tion for monocytic leukemia, compared in the genital and perianal areas, and have
with lymphocytic leukemia, which usually been reported on the lower abdominal walls,
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140 CA-ACANCER
JOURNAL
FORCLINICIANS
Almost all affected women have fibrocys
tic changes of the breast, and many of these
women ultimately develop breast cancer.
Thyroid tumors, both benign and malig
nant, are frequent (75 percent). Cancers of
the lung and colon have been reported.
Polyps of the gastrointestinal tract (33 per
cent) are generally benign. The signifi
cance of Cowden's disease lies in its value
as a marker for the eventual development
of thyroid or breast disease.
Extensive polyps of the gastrointes
tinal tract, especially the colon and rectum,
also occur in Gardner's syndrome, another
autosomal dominant disorder (Fig. l6).21
In Gardner's syndrome, however, the po
tential for malignant degeneration is so high
(approaching 100 percent) that prophylac
tic colectomy may be indicated for patients
demonstrating multiple polyps on radio
logic examination. Skin lesions include
large, deforming epidermoid cysts, fibro
mas, lipomas, leiomyomas, tnchoepithe
liomas, and neurofibromas. Osteomas Fig. 21. Acanthosis nigricans.
involving the membranous bones of the
face and head occur in about 50 percent
of affected patients.
In contrast to the asymptomatic pre
malignant polyps of Gardner's syndrome,
the hamartomatous polyps of Peutz-Jeghers ‘¿V.
References
Bibliography
Braverman IM: Skin Signs of Systemic Disease, Callen JP: Cutaneous Aspects of Internal Dis
ed 2. Philadelphia, WB Saunders Co, 1981. ease. Chicago, Year Book Medical Publishers,
Inc. 1981.