A spectrum of inflammatory metastasis to skin vialymphatics: Three cases of carcinoma erysipeloidesSue Ellen Cox, MD, and Ponciano D. Cruz, Jr., MD Dallas, Texas
We report a case in which carcinoma erysipeloides was the first sign of the primary malignancy in a patient with a rare form of prostate carcinoma (mixed adenosquamous type) andtwo cases in which carcinoma erysipeloides was a marker of tumor recurrence in two patientswith breast carcinoma. The value of recognizing the distinctive inflammatory manifestationof carcinoma erysipeloides and the significance of dermal lymphatic involvement in this formof skin metastasis are discussed. (J AM ACAD DERMATOL 1994;30:304-7.)
Although visible inflammation is a hallmark ofmany benign skin disorders, it is not commonlypresent in cutaneous malignant metastasis. As a result, the significance of marked inflammatorychanges as a marker of metastatic skin disease maynot be recognized. We document three cases of carcinoma erysipeloides to emphasize the diagnosticvalue of identifying this distinctive form of cutaneous metastasis.
CASE REPORTS
Case 1
A 56-year-old man had an enlarged prostate gland and"cellulitis" in the inguinal area for 2 months that was recalcitrant to antibiotic treatment. Examination revealedred to violaceous papules that coalesced into tender,indurated plaques in the inguinal area and on the upperright thigh (Fig. I).
Laboratory studies revealed a carcinoembryonic antigen of 35 ng/rnl (normal, 5 to 10 ng/rnl) and a prostatespecific antigen of7.4 ng/rnl (normal, <4 ng/ml). A chestx-ray film, cystoscopy, and bone scan were normal.Abdominal and pelvic computed tomographic scansrevealed a retroperitoneal tumor that surrounded theright kidney.
Two punch biopsy specimens showed similar histologicfeatures: underneath a normal epidermis carcinomatouscells were distributed diffusely between collagen bundles.
From the Department of Dermatology. University of Texas Southwestern Medical Center.
Reprint requests: Sue Ellen Cox, MD, Department of Dermatology,University of Texas Southwestern Medical Center, 5323 HarryHines Blvd., Dallas, TX 75235-9069.
Copyright ,.', 1994 hy the American Academy of Dermatology, lne.
0190-9622/94/$3.00+0 16/4/49861
304
A high-power view (Fig. 2) showed dilated dermallymphatics filled with malignant cells.
A random prostate biopsy specimen revealed ductaladenocarcinoma with prominent glandular structures.An inguinal lymph node biopsy specimen showed similarmalignant cells with squamous differentiation such aswell-defined tonofilaments and intercellular bridges; thisled to a diagnosis of a mixed adenosquamous type ofprostate carcinoma. Special stains demonstrated no reactivity for prostate-specific antigen, o-fetoprotein, or human chorionic gonadotropin; staining with periodic acidSchiff and mucicarmine was positive.
The patient did not respond to two cycles ofVP-16 andcis-platinum therapy. Radiation therapy was also ineffective. He died less than I year after diagnosis.
Case 2
A 43-year-old woman had an enlarging mass in herright breast associated with redness of the overlying skin.The redness subsequently disappeared, leaving a yellowdiscoloration.
The patient underwent modified right radical mastectomy. Histopathologic findings revealed three separatemedullary carcinomas. Metastasis to the right axillarylymph nodes then occurred, for which she underwentchemotherapy and radiation therapy. Four years later shehad a modified radical mastectomy of the left breast; histopathologic findings revealed infiltrating ductal carcinoma. She was treated with 12 cycles of chemotherapy(eMF), two courses of -v-radiation, and hyperthermia.
Seven years after her modified right radical mastectomy erythematous plaques with areas of yellow crustingdeveloped on the right anterior aspect of the chest walland similar but more indurated plaques developed outsideof the radiation port (Fig. 3). Telangiectasia and a lightbrown pigmentation were also present, which was consistent with postradiation dermatitis. However, skin biopsyspecimens revealed metastatic breast carcinoma.
Journal of the American Academy of DermatologyVolume 30, Number 2, Part 2 Cox and Cruz 305
Fig. 1. Case 1. Carcinoma erysipeloides caused by prostatic carcinoma.Fig. 2. High-power view of dermal lymphatics containing malignant cells.
Fig. 3. Case 2. Carcinoma erysipeloidescaused by recurrent intraductal breast carcinoma.Fig. 4. Case 3. Carcinoma erysipeloidescaused by recurrent intraductal breast carcinoma.
Case 3
A 56-year-old woman had a mass in her right breast,for which she underwent a modified radical mastectomy.Histopathologic findings showed poorly differentiated in-
filtrating ductal carcinoma; 17 axillary lymph nodes hadmetastatic involvement. Three months after mastectomyand 6 weeks after chemotherapy had begun she had redspots on the right arm that were thought to represent ir-
306 Cox and CruzJournal of the American Academy of Dermatology
February 1994
Table II. Manifestations of skin metastasis fromprostate cancer
Table I. Primary cancers other than breastcancer reported in association with inflammatoryskin metastasis
Manifestation Reference Nos.
Primary cancers
LungOvaryStomachTonsilsPancreasRectumColonParotidUterusProstate
Reference No.
9101010II12131415
Present report
Firm violaceous nodulesUlcerating tumorsVascular lesionsGeneralized pruritusNodules simulating scalp
sebaceous cystsTurban tumorsZosteriform lesionsSister Mary Joseph's nodule
of the umbilicusCarcinoma erysipeloides
16, 17, 1819202122
232425
Present report
ritant contact dermatitis from tape. Examination revealed an edematous right arm and brightly erythematous plaques studded with 2 to 3 mm papules (Fig. 4). Askin biopsy specimen revealed metastatic breast carcinoma.
DISCUSSION
As early as 1816 the occurrence of inflammatoryskin changes overlying breast tumors was consideredan "unpropitious" sign. 1 By 1889 it had becomeclear that the development of cutaneous inflammation over breast cancer correlated in many cases withmigration of malignant cells into dermallymphatics.2 Lee and Tannenbaum- in 1924 were probablythe first to report a large series (28 cases) of breastcancers associated with inflammatory skin changes,a condition they named inflammatory carcinoma.In 1931 Rast.:h4 introduced the term carcinomaerysipelatoides to denote the erysipelas-like development of red indurated skin with sharply marginated borders in association with skin metastasis.Both terms have subsequently been used almost interchangeably, particularly with respect to breastcarcinoma with inflammatory skin changes associated with invasion of dermal lymphatics.
Only a small portion of cases of breast carcinomaappear as inflammatory carcinoma or carcinomaerysipeloides (1% to 4% in the United States). 5 Mostof these patients have intraductal breast cancer," aswas true of the patients we described in cases 2 and3. It should be noted that the patient in case 2 initially had medullary carcinoma of the right breast,but a primary intraductal carcinoma of the leftbreast subsequently developed. Inflammatorychanges were seen with both of these breast cancers.A retrospective study of 89 patients with inflamma-
tory breast carcinoma indicated that erythema(51%) and a palpable breast mass (51%) were themost common features, followed by breast enlargement (43%) and, less frequently, increased warmth,edema, nipple retraction, and itching." The medianonset of inflammatory skin changes before diagnosis of the malignancy was 10 weeks.7
Carcinoma erysipeloides is only one of severalmanifestations of breast cancer that spread to skinvia lymphatics. Other manifestations include nodular carcinoma, telangiectatic carcinoma, and carcinoma en cuirasse.' Nodular carcinoma is characterized by noninflammatory, firm nodules thathistologically demonstrate grouped tumor cells indermal stroma and lymphatics and varying amountsof fibrosis. Telangiectatic carcinoma denotes thepresence of purpuric papules or plaques in skinoverlying the breast tumor; carcinomatous cells arepresent in the superficial dermal lymphatics. Finally,carcinoma en cuirasse refers to the peau d'orangeskin changes that can progress into more markedinduration and thickening; many reported cases hadmarked fibrosis and a paucity of tumor cells.
Although carcinoma erysipeloides is most commonly caused by breast carcinoma, it has also beenlinked to other carcinomas (Table I). To the best ofour knowledge, however, it has not been reportedpreviously in association with adenosquamous prostate carcinoma. In fact, almost all skin metastasesfrom prostate carcinoma appear as firm red to violaceous nodules (Table II). Several additional aspects of our patient with prostate carcinoma arcworth noting. First, the inflammatory skin metastasis was the first sign of the malignancy. Second,mixed adenosquamous prostate carcinoma is rare;by far the most common type of prostate cancer is
Journal of the American Academy of DermatologyVolume 30, Number 2, Part 2
adenocarcinoma of the acinar type. 26 Third, the caseillustrates lymphatic spread by prostate cancer toskin sites close to the primary tumor, such as the inguinal and genital areas and the lowerabdomen. 27,28
It is not clear why some cutaneous metastases arecharacterized by more inflammation than others.Possibly, particular types of malignancy (e.g., intraductal breast carcinoma) possess inherent propertiescapable of inciting greater inflammation. A secondfactor is heterogeneity in the host response to thespread of the tumor. It should be emphasized, however, that dermal lymphatic involvement is anessential feature shared by cases of inflammatorycarcinoma. This is consistent with the fact that cancers that tend to metastasize via the lymphatics (e.g.,breast carcinoma) are also the ones most commonlyassociated with carcinoma erysipeloides.
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Cox and Cruz 307
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