|Axillary and Groin Rashes in the Elderly: Don't Forget Cancer!|
Axillary and Groin Rashes in the Elderly: Don't Forget Cancer!
Lorraine Young, M.D.
A 92-year-old white female presented with a 3-month history of a pruritic rash in her right axilla. Topical steroid and antifungal creams were given, but they did not help, so she was referred to Dermatology for eval-uation. Her past medical history was unremarkable. On exam, a 4 cm x 4 cm erythematous, scaly plaque was noted in her right axilla (Figure 1). A complete skin examination was otherwise unremarkable. There was no breast nodule, nipple discharge, or axillary adenopathy.
A 73-year-old white male presented with a 4-month history of a pruritic rash in his groin. He also was treated with topical steroid and antifungal creams without benefit, and was referred to Dermatology. On examination, poorly marginated erythematous and scaly plaques were observed both in the right and left groin (Figure 2). The rest of his skin examination was normal, and there was no inguinal adenopathy.
Because neither patient responded to antifungal and steroid creams, biopsies were performed. In both cases, Paget cells, with their characteristic large, atypical nuclei and abundant pale-staining cytoplasm, were observed in the epidermis (Figure 3). Histochemical stains of the Paget cells were positive for cytokeratin 7 (Ck7) and carcinoembryonic antigen (CEA), and negative for HMB 45.
Based upon the clinical presentation and histopathology, a diagnosis of extramammary Paget's disease (EMPD) was made in both patients. Since Paget cells can invade underlying adnexal structures or regional tissues, or migrate to the epithelium from these same tissues, a systemic cancer work-up was
Figure 3. Skin biopsies, stained with hematoxylin and eosin, from the 92-year-old female (left) and from the 73-year-old male (right). Paget cells, with large, atypical nuclei and abundant pale-staining cytoplasm, are marked with arrows.
recommended. Because of the proximity of the axilla to the breast, associated breast cancer was of partic-ular concern in the 92-year-old female patient. Her evaluation for an internal malignancy, which included a mammogram, was negative. Her EMPD was treated with wide surgical excision. The 73-year-old male patient refused further evaluation, including a urogen-ital workup, but agreed to non-surgical therapy. Five percent imiquimod cream was applied daily for 6 weeks. Both patients were completely free of lesions at their 2-month follow-up skin examinations.
Patients commonly present to primary care physicians with pruritic, erythematous, and scaly plaques in intertriginous regions, such as the axilla and/or groin. Typically, the differential diagnosis includes sebor-rheic dermatitis, intertrigo, eczema, and psoriasis, for which topical steroids are useful, and tinea and candida, for which antifungal creams are useful. Not infrequently, patients are given steroid and antifungal creams simultaneously, and the skin lesions resolve despite the fact that no clear diagnosis was ever made.
When the lesions fail to resolve, however, as in the 2 patients described here, the differential diagnosis must be expanded to include cancer, such as Bowen's disease, mycosis fungoides, and EMPD. While each of these diseases can yield similarly appearing skin lesions, EMPD should be suspected strongly when the eruption involves skin containing apocrine glands. Extramammary Paget's disease usually develops in patients 70 years or older, typically Caucasians, and more commonly females. The onset of the eruption is insidious, and the disease spreads slowly. Extramammary Paget's disease is usually pruritic, but may be painful. Erythematous and scaly plaques are observed in areas of apocrine glands; the vulva, anogenital and anorectal regions are the most common, with the axilla being less common.1 Rarely, the disease occurs in modified apocrine glands, including the Moll's glands of the eyelid, and the ceruminal glands of the external auditory canal.2 There are 2 reports of ectopic EMPD on the face.3, 4
A skin biopsy, along with several histochemical stains, are required to make the diagnosis of EMPD. The key histological features are Paget cells, which have large and atypical nuclei and abundant pale-staining cytoplasm. These can be single or in clusters and are dispersed between the keratinocytes and can extend into the adnexal structures of the skin. The histological differential diagnosis is usually EMPD, malignant melanoma, and Bowen's disease.
To differentiate these diseases, the pathologist uses several immunohistochemical stains. Common stains include cytokeratins Ck7 and Ck20 (fibrous proteins in the epithelium), CEA (eccrine and apocrine cells), and S100 and HMB 45 (melanoma). Other stains useful for the identification of EMPD are gross cystic disease fluid protein-15 and epithelial antigen stain.5
Even with a biopsy and immunohistochemical stains, however, it is sometimes challenging to identify EMPD. A case was recently reported of a 77-year-old man presenting with a 1-cm nodule in his left groin, surrounded by a 10-cm area of erythema with scale.6 The biopsy and immunohistochemical stains suggested the diagnosis of Merkel cell carcinoma with candidiasis. When the "candidiasis" did not respond to ketoconazole, however, a dermatologist was consulted. A clinical suspicion for EMPD led to a second biopsy, which confirmed EMPD. Rarely, one observes combinations of axillary and anogenital EMPD, mammary Paget's disease (MPD) with EMPD, and even EMPD and mycosis fungoides simultaneously in the axilla and groin.
Extramammary Paget's disease is an intraepithelial adenocarcinoma in situ which may become invasive and even metastasize. The tumor cells within the epithelium are thought to arise from apocrine gland ducts or pluripotent germinative cells. Alternatively, the disease may arise from pagetoid spread from an underlying adnexal tumor or from an internal malig-nancy.
The pathogenesis of EMPD is poorly understood. Recently, however, over-expression of PIG7/LITAF mRNA was reported to be involved in EMPD carcinogenesis.7
Extramammary Paget's disease is associated with an underlying or distal malignancy in 24% to 70% of patients.8,9 Immunohistochemical stains do not differentiate intraepithelial in-situ disease from that arising from an underlying adnexal structure or regional internal malignancy. Thus, one must always search diligently for a tumor in adjacent and regional tissues. Particularly important is the examination of the bladder and rectum, but the prostate, urethra, and cervix can also be a source of EMPD. More distant organs also need to be evaluated, particularly the breast.
Surgery can successfully treat smaller lesions, as in the case of our 92 year-old female patient. A recent case of perianal EMPD was reported where the patient was treated with wide surgical excision. He remained disease-free 1-1/2 years later.10 Since some lesions are multifocal and ill-defined, Mohs micrographic surgery (MMS) can be used instead of wide excision, and this approach may lower the recurrence rate.11,12
Nonsurgical options can be helpful in treating multiple and widespread lesions of EMPD, as in the case of our 73-year-old male patient, and include radiotherapy13 and 5% imiquimod cream14 (an immunomodulator). A patient with scrotal EMPD was initially treated with MMS, but developed a recurrence 4 years later. Imiquimod cream was then used daily for 6 weeks, with clinical and histological eradication. No recurrence was noted at the 6-month follow-up examination.
Long-term follow up is advised. The persistence or recurrence of EMPD is of particular concern because of the multifocal nature of the disease and because ill-defined margins make treatment approaches problem-atic. Also, progression to invasive disease and even metastases can occur.
In summary, a 92-year-old female and a 73-year-old male presented with persistent axillary and groin plaques, respectively. The usual differential diagnosis includes seborrheic dermatitis, intertrigo, eczema, psoriasis, tinea, and yeast. However, when lesions persist despite topical steroid and anti-fungal therapy, the differential diagnosis must be expanded to include cancers, such as Bowen's disease, mycosis fungoides, and EMPD. A skin biopsy with immunohistochem-ical stains is required to establish the diagnosis. Extramammary Paget's disease most commonly arises from an intraepithelial adenocarcinoma, which can be invasive and even metastasize. Additionally, it can also develop from an underlying adnexal tumor or internal malignancy, so a thorough systemic work-up for cancer is indicated. There are surgical and nonsur-gical treatment options, depending on whether the disease is focal or widespread. Follow-up is essential because of the risk of persistence, recurrence, or progression of the disease to underlying structures or regional tissues. Intertriginous rashes are commonly seen by the primary care physician, and cancer needs to be considered when these "rashes" persist despite the usual treatment modalities. Extramammary Paget's disease should be high on the differential when a rash in an elderly patient persists in areas of skin containing apocrine glands.
Submitted on April 1, 2005