CASE REPORT
Cancers Mimicking Fungal Infections Barry Ladizinski, MD; Afsaneh Alavi, MD; Jay Jambrosic, MD; Nisha Mistry, MD; and R. Gary Sibbald, MD, MEd, BSc, FRCPC(Med Derm), MACP, FAAD, MAPWCA tation. The cutaneous eruption was diagnosed as tinea corporis, but it was not responsive to multiple trials of topical antifungal therapy. Physical examination revealed diffuse confluent annular erythema with distinct borders on the bilateral breasts and abdomen (Figure 1). Microscopic examination of skin surface scale utilizing potassium hydroxide was negative for fungal hyphae. Skin punch biopsy of the right breast demonstrated clusters of large, pleomorphic atypical epithelial cells within superficial lymphatic channels, compatible with metastatic carcinoma (Figures 2A and B). Immunohistochemical analysis showed positive staining with thyroid transcription factor 1 (TTF1) and cytokeratin 7 (CK7), confirming metastatic lung carcinoma, and blood vessels stained positively with anti-D2 antibody (D2-40), confirming lymphatic involvement (Figures 2C and D).
ABSTRACT Primary and metastatic malignancies may occasionally mimic or coexist with cutaneous fungal infections. The authors report 3 cases of cancers that were initially presumed to be cutaneous fungal infections. Dermatologists should maintain a low threshold for skin biopsy in patients with persistent or refractory fungal infections. KEYWORDS: fungal infection, mycosis fungoides, skin metastases, cutaneous T-cell lymphoma, squamous cell carcinoma ADV SKIN WOUND CARE 2014;27:301Y5
Fungal infections are a common reason for dermatology visits. Cancers infiltrating the skin, whether primary or metastatic, may occasionally mimic or coexist with cutaneous fungal infections.1Y5 Therefore, malignancy is an important consideration in patients presenting with a presumed dermatophyte infection that is unresponsive to conventional antifungal therapy. The need for early and accurate diagnosis of malignancy, even when the suspicion is low, cannot be overemphasized because of the significant impact on prognosis and biopsy is recommended in refractory lesions. The authors report 3 cases of cutaneous malignant secondary infiltrations or primary skin cancers that were initially presumed to be a cutaneous fungal infection.
CASE REPORT 2 A healthy 70-year-old man presented with a persistent asymptomatic rash that was not responsive to multiple courses of topical antifungal therapy. Physical examination revealed localized erythematous patches on the right axilla and left groin (Figure 3A). Skin biopsy demonstrated a lichenoid lymphocytic infiltrate with prominent epidermotropism (a band of cells clustered around the dermal-epidermal junction with migration into the epidermis). The lymphocytic cell atypia was compatible with cutaneous T-cell lymphoma, with the epidermotropism diagnostic of the mycosis fungoides (MF) histological pattern (Figure 3B).
CASE REPORT 1
CASE REPORT 3
A 56-year-old woman presented with an asymptomatic, progressive rash on both breasts of 5 months’ duration. The medical history was significant for lung cancer that achieved a chemotherapy-induced clinical remission 2 years before presen-
A 78-year-old man with a longstanding history of diabetes presented with an ulcer in the fourth and fifth interdigital space on the right foot that was complicated by a secondary infection (Figure 4A). Toe-web bacterial swab culture grew Pseudomonas
Barry Ladizinski, MD, is an MPH/MBA candidate at Johns Hopkins University, Baltimore, Maryland. Afsaneh Alavi, MD, is a Dermatology and Wound Care Consultant at the Women’s College Hospital and the University of Toronto, Ontario, Canada. Jay Jambrosic, MD, is a Dermatopathology Consultant at the Women’s College Hospital, University of Toronto, and Life Lab Dermatopathology, Toronto. Nisha Mistry, MD, is Adjunct Lecturer at the University of Toronto. R. Gary Sibbald, MD, MEd, BSc, FRCPC(Med Derm), MACP, FAAD, MAPWCA, is Professor of Public Health and Medicine, University of Toronto, Ontario, Canada; Director, International Interprofessional Wound Care Course & Masters of Science in Community Health (Prevention & Wound Care), Dalla Lana School of Public Health, University of Toronto; Past President, World Union of Wound Healing Societies; Course Coordinator, International Interprofessional Wound Care Course at New York University Medical Center, and Clinical Editor, Advances in Skin & Wound Care, Philadelphia, Pennsylvania. Dr Ladizinski has disclosed that he has no financial relationships related to this article. Dr Alavi has disclosed that she was a consultant to Galderma, Valeant, and Abbott and was renumerated for travel expenses from Leo and Stiefel Laboratories. Dr Jambrosic has disclosed that he is employed by Ontario Health Insurance Canada, and he has provided expert testimony for the Canadian Medical Protective Association. Dr Mistry has disclosed that she is a consultant to Abbott and Janssen; was a member of the speakers’ bureau for Galderma, Leo, and Triton; and was a member of the speakers’ bureau for Valeant and Valeo. Dr Sibbald has disclosed that he is a board member of 3M, BSN, Coloplast, Covidien, Gaymar, KCI, Systagenix, Mo¨lnlycke, Registered Nurses Association of Ontario, Hollister Limited, and Healthpoint; was a member of the speakers’ bureau for 3M, BSN, Coloplast, Gaymar, KCI, Systagenix, Mo¨lnlycke, Hollister Limited, Valeant, and Stiefel Laboratories, Inc; and his employer, the University of Toronto, was a research participant with 3M, BSN, Canadian International Development Agency, Coloplast, Covidien, Government of Ontario, KCI, Johnson & Johnson, Systagenix, Mo¨lnlycke, Registered Nurses Association of Ontario, Exciton Technologies, Hollister Limited, Healthpoint, Valeant, Shire Regenerative Medicine, Abbott Laboratories, and Community Care Access Centers. Submitted May 30, 2013; accepted in revised form November 5, 2013. WWW.WOUNDCAREJOURNAL.COM
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ADVANCES IN SKIN & WOUND CARE & JULY 2014
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
CASE REPORT
Figure 1. DIFFUSE ANNULAR ERYTHEMA WITH DISTINCT BORDERS ON THE BREASTS OF A 56-YEAR-OLD WOMAN
diabetic neuropathy, but the ulcer persisted. Subsequent skin biopsy of the ulcer demonstrated invasive moderately differentiated squamous cell carcinoma (Figure 4B).
DISCUSSION
aeruginosa, and fungal scraping of a toenail confirmed the presence of fungal organisms. He received antibiotics for the infection, and the local toe-web ulcer was treated for 1 year as a complication of
Although rare, systemic or cutaneous malignancies can occasionally mimic fungal infection.1Y5 Annular erythema of the chest wall has been previously reported in 3 women with known breast cancer that was in remission.1 The patients were all previously treated with combination chemotherapy without evidence of recurrence until they presented with chest wall erythema. Subsequent skin biopsies of all 3 patients showed invasive ductal carcinoma within lymphatic channels that stained positively for human epidermal growth factor receptor.2 The differential diagnosis of annular erythema of the breasts is broad and includes dermatophyte infection, granuloma annulare, pityriasis rosea, psoriasis, annular erythema, cutaneous
Figure 2. CASE REPORT 1 HISTOPATHOLOGY RESULTS
A and B, Histopathology showed nests of atypical epithelial cells within lymphatic channels, consistent with metastatic cancer (hematoxylin-eosin stain, original magnification 100). C and D, Immunohistochemical analysis showed positive staining with TTF1 and CK7 confirming metastatic lung cancer (original magnification 200). ADVANCES IN SKIN & WOUND CARE & VOL. 27 NO. 7
302
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CASE REPORT
Figure 3. CASE REPORT 2
A and B, Erythematous patches on the right axilla and left groin of a 70-year-old man. C, Histopathology showed a lichenoid lymphocytic infiltrate with epidermotropism, consistent patch-stage MF (hematoxylin-eosin stain, original magnification 200).
sarcoidosis lesions, discoid lupus, and other less common dermatological conditions. Dermatophytes are a group of fungi that require keratin for growth. They may cause superficial infections of the skin, hair, and nails. The characteristic septate hyphae produced by dermatophytes can be identified by treating skin keratin scrapings with potassium hydroxide on a slide and cover slip for light microscopy. Yeast infections caused by Candida albicans can be distinguished from dermatophytes infection by the predominance around skin folds with excess moisture or sweating with bright red erythema, satellite papules, and pustules with an absence of central clearing and the bright red annular border. WWW.WOUNDCAREJOURNAL.COM
Tinea corporis (fungus on the body other than folds, palms, soles, nails) typically presents as well demarcated annular scaly plaques with central clearing and slightly elevated red edge. Use of a topical steroid may mask the typical clinical appearance of cutaneous fungus infection, known as tinea incognito. Clinically, an absence of surface scale and lack of irregular involvement of hair follicles distal to the advancing margin are subtle clues that fungal infection may not be the most likely diagnosis. The diagnosis of tinea is usually made clinically with confirmation from scalpel blade scraping of the surface scale at the edge for either microscopic examination of septate hyphae (potassium hydroxide staining) or culture for fungus (on Sabouraud medium) to confirm the diagnosis. A skin biopsy may be warranted in certain patients, particularly those with refractory disease. The diagnosis of tinea is sometimes challenging, especially in tinea incognito, and the biopsy should be taken from the active edge of atypical or nonresponsive lesions with microscopic examination and staining with the periodic acidYSchiff method to identify or confirm the absence of dermatophyte fungal hyphae. Cell-marker staining of atypical cell infiltrate will identify malignant cells and help to determine the type of the metastatic cell including the following: TTF1 (a marker of lung cells); CK7 (a marker of keratin found in breast, lung, ovary, and urinary tract epithelium); and D2-40 (a marker for lymphatic endothelium).6 Of note, skin metastases occur in approximately 5% of visceral malignancies with metastatic spread.7 Metastatic breast cancer is associated with up to 30% of cases having cutaneous metastases, whereas only 3% to 4% of persons with metastatic lung cancer have cutaneous metastatic lesions associated with their cancer,8 as was the case with this patient. The MF variant of cutaneous T-cell lymphoma should also be considered in patients with recalcitrant tinea infections, and both conditions may occasionally coexist. The name ‘‘mycosis fungoides’’ is a historical name from the early 19th century that serves as a reminder that lymphoma can be mimicked by a cutaneous fungal infection. Several cases of refractory mycoses superimposed on MF have been reported.2Y4 Fungi isolated in these patients included C albicans,2 Trichophyton rubrum,2 and Trichophyton mentagrophytes.3 Axillary MF mimicking tinea corporis or intertriginous tinea infection has also been reported,5 and this case serves as another example of this type of presentation. Mycosis fungoides is the most common subtype of cutaneous T-cell lymphoma, with a clinical presentation that is skin predominant and has potential for involvement of lymph nodes and internal organs. The disease usually appears in adults between ages 55 and 60 years old, presenting with multiple patches, plaques, nodules, or even erythroderma (generalized red skin).
303
ADVANCES IN SKIN & WOUND CARE & JULY 2014
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
CASE REPORT
Figure 4. CASE REPORT 3
A, Ulcer in the fourth and fifth toe web space on the right foot of a 78-year-old man. B, Histopathology showed nests of atypical keratinocytes within the dermis, consistent with squamous cell carcinoma (hematoxylin-eosin stain, original magnification 200).
A combination of clinical criteria along with histological and laboratory investigations (eg, immunophenotyping, flow cytometry, T-cell receptor gene rearrangement studies) is required for the diagnosis and staging of cases with MF. Patients with a high index of suspicion for MF may require multiple skin biopsies to confirm the diagnosis. The biopsy for suspected MF should be processed for regular histology and cell markers. The prognosis is variable, and the MF treatments include the following: high-potency topical steroids (lower potencies in the face or folds) or topical nitrogen mustard (mechlorethamine) are often successful with cutaneous predominant disease; phototherapy (often psoralens plus ultraviolet A or narrowband ultraviolet B); systemic therapy (oral retinoids interferon-alfa, biologics, targeted therapy, or chemotherapy with internal involvement); and other modalities including total body electron beam radiation therapy.9 Cutaneous squamous cell carcinoma may also occasionally be confused with a fungal infection. This is particularly true when the lesion is in a location typical of a fungal infection, as was the case with the authors’ patient, whose carcinoma mimicked toe-web erosion (erosio interdigitalis). Although there have been multiple cases of malignant melanoma presenting as diabetic foot ulcers,10Y13 there are limited reports of squamous cell carcinoma presenting as interdigital diabetic foot ulcers.11 Some case reports have documented squamous cell carcinoma superimposed on diabetic foot ulcers; however, this case is unique in that it developed in the toe web, where fungal infection may have led to ADVANCES IN SKIN & WOUND CARE & VOL. 27 NO. 7
persistent inflammation, undetected by the presence of neuropathy, and followed by malignant transformation. Thus, it is important to consider malignancy in nonhealing ulcers. Features that suggest malignant transformation in a wound include chronic ulceration not responsive to treatment, granulation tissue beyond the wound margins, hypertrophic wound edges, and associated regional lymphadenopathy.9,14Y16
SUMMARY Fungal infections may occasionally mimic or coexist with neoplasms of the skin. Healthcare practitioners and dermatology specialists need to confirm the fungal etiology in refractory cases and, when negative or unresponsive, a skin biopsy is recommended. The early determination of a specific diagnosis is important because the management and outcome of these 2 processes are entirely different. Further, the gravity of delaying diagnosis of a malignancy is critical.
&
REFERENCES
304
1. Tan E, Kuper-Hommel M, Rademaker M. Annular erythema as a sign of recurrent breast cancer. Australas J Dermatol 2010;51:135-8. 2. Alteras I, David M, Feuerman EJ, Morojonski G. Widespread cutaneous candidiasis and tinea infection masking mycosis fungoides. Mycopathologia 1982;80:83-8. 3. Capella GL, Altomare GF. Mycosis on mycosis fungoides: zoophilic dermatophytosis selectively superimposed on pre-existing cutaneous T-cell lymphoma (mycosis fungoides) plaques. Mycoses 2003;46(1-2):67-70. 4. Hubert JN, Callen JP. Recalcitrant tinea corporis as the presenting manifestation of patch-stage mycosis fungoides. Cutis 2003;71:59-61. 5. Chave TA, Graham-Brown RA. Mycosis fungoides masquerading as tinea of the axilla. Clin Exp Dermatol 2002;27:66-7. WWW.WOUNDCAREJOURNAL.COM
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
CASE REPORT
6. Brunnstro¨m H, Johansson L, Jirstro¨m K, Jo¨nsson M, Jo¨nsson P, Planck M. Immunohistochemistry in the differential diagnostics of primary lung cancer: an investigation within the Southern Swedish Lung Cancer Study. Am J Clin Pathol 2013;140: 37-46. 7. Lookingbill DP, Spangler N, Sexton FM. Skin involvement as the presenting sign of internal carcinoma. A retrospective study of 7316 cancer patients. J Am Acad Dermatol 1990;22:19-26. 8. Li WH, Tu CY, Hsieh TC, Wu PY. Zosteriform skin metastasis of lung cancer. Chest 2012; 142:1652-4. 9. Zinzani PL, Ferreri AJ, Cerroni L. Mycosis fungoides. Crit Rev Oncol Hematol 2008;65: 172-82. 10. Kong MF, Jogia R, Jackson S, Quinn M, McNally P, Davies M. When to biopsy a foot ulcer? Seven cases of malignant melanoma presenting as foot ulcers. Pract Diabetes Int 2008;25:5-8.
WWW.WOUNDCAREJOURNAL.COM
11. Panda S, Khanna S, Singh SK, Gupta SK. Squamous cell carcinoma developing in a diabetic foot ulcer. Int J Low Extrem Wounds 2011;10:101-3. 12. Misciali C, Dika E, Fanti PA, et al. Frequency of malignant neoplasms in 257 chronic leg ulcers. Dermatol Surg 2013;39:849-54. 13. Meaume S, Fromantin I, Teot L. Neoplastic wounds and degenerescence. J Tissue Viability 2013;22(4):122-30. 14. Tang JC, Vivas A, Rey A, Kirsner RS, Romanelli P. Atypical ulcers: wound biopsy results from a university wound pathology service. Ostomy Wound Manage 2012;58(6):20-22, 24, 26-29. 15. Dowsett C. Malignant fungating wounds: assessment and management. Br J Community Nurs 2002;7:394-400. 16. Senet P, Combemale P, Debure C, et al. Malignancy and chronic leg ulcers: the value of systematic wound biopsies: a prospective, multicenter, cross-sectional study. Arch Dermatol 2012;148:704-8.
305
ADVANCES IN SKIN & WOUND CARE & JULY 2014
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Cancers Mimicking Fungal Infections Barry Ladizinski, MD; Afsaneh Alavi, MD; Jay Jambrosic, MD; Nisha Mistry, MD; and R. Gary Sibbald, MD, MEd, BSc, FRCPC(Med Derm), MACP, FAAD, MAPWCA tation. The cutaneous eruption was diagnosed as tinea corporis, but it was not responsive to multiple trials of topical antifungal therapy. Physical examination revealed diffuse confluent annular erythema with distinct borders on the bilateral breasts and abdomen (Figure 1). Microscopic examination of skin surface scale utilizing potassium hydroxide was negative for fungal hyphae. Skin punch biopsy of the right breast demonstrated clusters of large, pleomorphic atypical epithelial cells within superficial lymphatic channels, compatible with metastatic carcinoma (Figures 2A and B). Immunohistochemical analysis showed positive staining with thyroid transcription factor 1 (TTF1) and cytokeratin 7 (CK7), confirming metastatic lung carcinoma, and blood vessels stained positively with anti-D2 antibody (D2-40), confirming lymphatic involvement (Figures 2C and D).
ABSTRACT Primary and metastatic malignancies may occasionally mimic or coexist with cutaneous fungal infections. The authors report 3 cases of cancers that were initially presumed to be cutaneous fungal infections. Dermatologists should maintain a low threshold for skin biopsy in patients with persistent or refractory fungal infections. KEYWORDS: fungal infection, mycosis fungoides, skin metastases, cutaneous T-cell lymphoma, squamous cell carcinoma ADV SKIN WOUND CARE 2014;27:301Y5
Fungal infections are a common reason for dermatology visits. Cancers infiltrating the skin, whether primary or metastatic, may occasionally mimic or coexist with cutaneous fungal infections.1Y5 Therefore, malignancy is an important consideration in patients presenting with a presumed dermatophyte infection that is unresponsive to conventional antifungal therapy. The need for early and accurate diagnosis of malignancy, even when the suspicion is low, cannot be overemphasized because of the significant impact on prognosis and biopsy is recommended in refractory lesions. The authors report 3 cases of cutaneous malignant secondary infiltrations or primary skin cancers that were initially presumed to be a cutaneous fungal infection.
CASE REPORT 2 A healthy 70-year-old man presented with a persistent asymptomatic rash that was not responsive to multiple courses of topical antifungal therapy. Physical examination revealed localized erythematous patches on the right axilla and left groin (Figure 3A). Skin biopsy demonstrated a lichenoid lymphocytic infiltrate with prominent epidermotropism (a band of cells clustered around the dermal-epidermal junction with migration into the epidermis). The lymphocytic cell atypia was compatible with cutaneous T-cell lymphoma, with the epidermotropism diagnostic of the mycosis fungoides (MF) histological pattern (Figure 3B).
CASE REPORT 1
CASE REPORT 3
A 56-year-old woman presented with an asymptomatic, progressive rash on both breasts of 5 months’ duration. The medical history was significant for lung cancer that achieved a chemotherapy-induced clinical remission 2 years before presen-
A 78-year-old man with a longstanding history of diabetes presented with an ulcer in the fourth and fifth interdigital space on the right foot that was complicated by a secondary infection (Figure 4A). Toe-web bacterial swab culture grew Pseudomonas
Barry Ladizinski, MD, is an MPH/MBA candidate at Johns Hopkins University, Baltimore, Maryland. Afsaneh Alavi, MD, is a Dermatology and Wound Care Consultant at the Women’s College Hospital and the University of Toronto, Ontario, Canada. Jay Jambrosic, MD, is a Dermatopathology Consultant at the Women’s College Hospital, University of Toronto, and Life Lab Dermatopathology, Toronto. Nisha Mistry, MD, is Adjunct Lecturer at the University of Toronto. R. Gary Sibbald, MD, MEd, BSc, FRCPC(Med Derm), MACP, FAAD, MAPWCA, is Professor of Public Health and Medicine, University of Toronto, Ontario, Canada; Director, International Interprofessional Wound Care Course & Masters of Science in Community Health (Prevention & Wound Care), Dalla Lana School of Public Health, University of Toronto; Past President, World Union of Wound Healing Societies; Course Coordinator, International Interprofessional Wound Care Course at New York University Medical Center, and Clinical Editor, Advances in Skin & Wound Care, Philadelphia, Pennsylvania. Dr Ladizinski has disclosed that he has no financial relationships related to this article. Dr Alavi has disclosed that she was a consultant to Galderma, Valeant, and Abbott and was renumerated for travel expenses from Leo and Stiefel Laboratories. Dr Jambrosic has disclosed that he is employed by Ontario Health Insurance Canada, and he has provided expert testimony for the Canadian Medical Protective Association. Dr Mistry has disclosed that she is a consultant to Abbott and Janssen; was a member of the speakers’ bureau for Galderma, Leo, and Triton; and was a member of the speakers’ bureau for Valeant and Valeo. Dr Sibbald has disclosed that he is a board member of 3M, BSN, Coloplast, Covidien, Gaymar, KCI, Systagenix, Mo¨lnlycke, Registered Nurses Association of Ontario, Hollister Limited, and Healthpoint; was a member of the speakers’ bureau for 3M, BSN, Coloplast, Gaymar, KCI, Systagenix, Mo¨lnlycke, Hollister Limited, Valeant, and Stiefel Laboratories, Inc; and his employer, the University of Toronto, was a research participant with 3M, BSN, Canadian International Development Agency, Coloplast, Covidien, Government of Ontario, KCI, Johnson & Johnson, Systagenix, Mo¨lnlycke, Registered Nurses Association of Ontario, Exciton Technologies, Hollister Limited, Healthpoint, Valeant, Shire Regenerative Medicine, Abbott Laboratories, and Community Care Access Centers. Submitted May 30, 2013; accepted in revised form November 5, 2013. WWW.WOUNDCAREJOURNAL.COM
301
ADVANCES IN SKIN & WOUND CARE & JULY 2014
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
CASE REPORT
Figure 1. DIFFUSE ANNULAR ERYTHEMA WITH DISTINCT BORDERS ON THE BREASTS OF A 56-YEAR-OLD WOMAN
diabetic neuropathy, but the ulcer persisted. Subsequent skin biopsy of the ulcer demonstrated invasive moderately differentiated squamous cell carcinoma (Figure 4B).
DISCUSSION
aeruginosa, and fungal scraping of a toenail confirmed the presence of fungal organisms. He received antibiotics for the infection, and the local toe-web ulcer was treated for 1 year as a complication of
Although rare, systemic or cutaneous malignancies can occasionally mimic fungal infection.1Y5 Annular erythema of the chest wall has been previously reported in 3 women with known breast cancer that was in remission.1 The patients were all previously treated with combination chemotherapy without evidence of recurrence until they presented with chest wall erythema. Subsequent skin biopsies of all 3 patients showed invasive ductal carcinoma within lymphatic channels that stained positively for human epidermal growth factor receptor.2 The differential diagnosis of annular erythema of the breasts is broad and includes dermatophyte infection, granuloma annulare, pityriasis rosea, psoriasis, annular erythema, cutaneous
Figure 2. CASE REPORT 1 HISTOPATHOLOGY RESULTS
A and B, Histopathology showed nests of atypical epithelial cells within lymphatic channels, consistent with metastatic cancer (hematoxylin-eosin stain, original magnification 100). C and D, Immunohistochemical analysis showed positive staining with TTF1 and CK7 confirming metastatic lung cancer (original magnification 200). ADVANCES IN SKIN & WOUND CARE & VOL. 27 NO. 7
302
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CASE REPORT
Figure 3. CASE REPORT 2
A and B, Erythematous patches on the right axilla and left groin of a 70-year-old man. C, Histopathology showed a lichenoid lymphocytic infiltrate with epidermotropism, consistent patch-stage MF (hematoxylin-eosin stain, original magnification 200).
sarcoidosis lesions, discoid lupus, and other less common dermatological conditions. Dermatophytes are a group of fungi that require keratin for growth. They may cause superficial infections of the skin, hair, and nails. The characteristic septate hyphae produced by dermatophytes can be identified by treating skin keratin scrapings with potassium hydroxide on a slide and cover slip for light microscopy. Yeast infections caused by Candida albicans can be distinguished from dermatophytes infection by the predominance around skin folds with excess moisture or sweating with bright red erythema, satellite papules, and pustules with an absence of central clearing and the bright red annular border. WWW.WOUNDCAREJOURNAL.COM
Tinea corporis (fungus on the body other than folds, palms, soles, nails) typically presents as well demarcated annular scaly plaques with central clearing and slightly elevated red edge. Use of a topical steroid may mask the typical clinical appearance of cutaneous fungus infection, known as tinea incognito. Clinically, an absence of surface scale and lack of irregular involvement of hair follicles distal to the advancing margin are subtle clues that fungal infection may not be the most likely diagnosis. The diagnosis of tinea is usually made clinically with confirmation from scalpel blade scraping of the surface scale at the edge for either microscopic examination of septate hyphae (potassium hydroxide staining) or culture for fungus (on Sabouraud medium) to confirm the diagnosis. A skin biopsy may be warranted in certain patients, particularly those with refractory disease. The diagnosis of tinea is sometimes challenging, especially in tinea incognito, and the biopsy should be taken from the active edge of atypical or nonresponsive lesions with microscopic examination and staining with the periodic acidYSchiff method to identify or confirm the absence of dermatophyte fungal hyphae. Cell-marker staining of atypical cell infiltrate will identify malignant cells and help to determine the type of the metastatic cell including the following: TTF1 (a marker of lung cells); CK7 (a marker of keratin found in breast, lung, ovary, and urinary tract epithelium); and D2-40 (a marker for lymphatic endothelium).6 Of note, skin metastases occur in approximately 5% of visceral malignancies with metastatic spread.7 Metastatic breast cancer is associated with up to 30% of cases having cutaneous metastases, whereas only 3% to 4% of persons with metastatic lung cancer have cutaneous metastatic lesions associated with their cancer,8 as was the case with this patient. The MF variant of cutaneous T-cell lymphoma should also be considered in patients with recalcitrant tinea infections, and both conditions may occasionally coexist. The name ‘‘mycosis fungoides’’ is a historical name from the early 19th century that serves as a reminder that lymphoma can be mimicked by a cutaneous fungal infection. Several cases of refractory mycoses superimposed on MF have been reported.2Y4 Fungi isolated in these patients included C albicans,2 Trichophyton rubrum,2 and Trichophyton mentagrophytes.3 Axillary MF mimicking tinea corporis or intertriginous tinea infection has also been reported,5 and this case serves as another example of this type of presentation. Mycosis fungoides is the most common subtype of cutaneous T-cell lymphoma, with a clinical presentation that is skin predominant and has potential for involvement of lymph nodes and internal organs. The disease usually appears in adults between ages 55 and 60 years old, presenting with multiple patches, plaques, nodules, or even erythroderma (generalized red skin).
303
ADVANCES IN SKIN & WOUND CARE & JULY 2014
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
CASE REPORT
Figure 4. CASE REPORT 3
A, Ulcer in the fourth and fifth toe web space on the right foot of a 78-year-old man. B, Histopathology showed nests of atypical keratinocytes within the dermis, consistent with squamous cell carcinoma (hematoxylin-eosin stain, original magnification 200).
A combination of clinical criteria along with histological and laboratory investigations (eg, immunophenotyping, flow cytometry, T-cell receptor gene rearrangement studies) is required for the diagnosis and staging of cases with MF. Patients with a high index of suspicion for MF may require multiple skin biopsies to confirm the diagnosis. The biopsy for suspected MF should be processed for regular histology and cell markers. The prognosis is variable, and the MF treatments include the following: high-potency topical steroids (lower potencies in the face or folds) or topical nitrogen mustard (mechlorethamine) are often successful with cutaneous predominant disease; phototherapy (often psoralens plus ultraviolet A or narrowband ultraviolet B); systemic therapy (oral retinoids interferon-alfa, biologics, targeted therapy, or chemotherapy with internal involvement); and other modalities including total body electron beam radiation therapy.9 Cutaneous squamous cell carcinoma may also occasionally be confused with a fungal infection. This is particularly true when the lesion is in a location typical of a fungal infection, as was the case with the authors’ patient, whose carcinoma mimicked toe-web erosion (erosio interdigitalis). Although there have been multiple cases of malignant melanoma presenting as diabetic foot ulcers,10Y13 there are limited reports of squamous cell carcinoma presenting as interdigital diabetic foot ulcers.11 Some case reports have documented squamous cell carcinoma superimposed on diabetic foot ulcers; however, this case is unique in that it developed in the toe web, where fungal infection may have led to ADVANCES IN SKIN & WOUND CARE & VOL. 27 NO. 7
persistent inflammation, undetected by the presence of neuropathy, and followed by malignant transformation. Thus, it is important to consider malignancy in nonhealing ulcers. Features that suggest malignant transformation in a wound include chronic ulceration not responsive to treatment, granulation tissue beyond the wound margins, hypertrophic wound edges, and associated regional lymphadenopathy.9,14Y16
SUMMARY Fungal infections may occasionally mimic or coexist with neoplasms of the skin. Healthcare practitioners and dermatology specialists need to confirm the fungal etiology in refractory cases and, when negative or unresponsive, a skin biopsy is recommended. The early determination of a specific diagnosis is important because the management and outcome of these 2 processes are entirely different. Further, the gravity of delaying diagnosis of a malignancy is critical.
&
REFERENCES
304
1. Tan E, Kuper-Hommel M, Rademaker M. Annular erythema as a sign of recurrent breast cancer. Australas J Dermatol 2010;51:135-8. 2. Alteras I, David M, Feuerman EJ, Morojonski G. Widespread cutaneous candidiasis and tinea infection masking mycosis fungoides. Mycopathologia 1982;80:83-8. 3. Capella GL, Altomare GF. Mycosis on mycosis fungoides: zoophilic dermatophytosis selectively superimposed on pre-existing cutaneous T-cell lymphoma (mycosis fungoides) plaques. Mycoses 2003;46(1-2):67-70. 4. Hubert JN, Callen JP. Recalcitrant tinea corporis as the presenting manifestation of patch-stage mycosis fungoides. Cutis 2003;71:59-61. 5. Chave TA, Graham-Brown RA. Mycosis fungoides masquerading as tinea of the axilla. Clin Exp Dermatol 2002;27:66-7. WWW.WOUNDCAREJOURNAL.COM
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
CASE REPORT
6. Brunnstro¨m H, Johansson L, Jirstro¨m K, Jo¨nsson M, Jo¨nsson P, Planck M. Immunohistochemistry in the differential diagnostics of primary lung cancer: an investigation within the Southern Swedish Lung Cancer Study. Am J Clin Pathol 2013;140: 37-46. 7. Lookingbill DP, Spangler N, Sexton FM. Skin involvement as the presenting sign of internal carcinoma. A retrospective study of 7316 cancer patients. J Am Acad Dermatol 1990;22:19-26. 8. Li WH, Tu CY, Hsieh TC, Wu PY. Zosteriform skin metastasis of lung cancer. Chest 2012; 142:1652-4. 9. Zinzani PL, Ferreri AJ, Cerroni L. Mycosis fungoides. Crit Rev Oncol Hematol 2008;65: 172-82. 10. Kong MF, Jogia R, Jackson S, Quinn M, McNally P, Davies M. When to biopsy a foot ulcer? Seven cases of malignant melanoma presenting as foot ulcers. Pract Diabetes Int 2008;25:5-8.
WWW.WOUNDCAREJOURNAL.COM
11. Panda S, Khanna S, Singh SK, Gupta SK. Squamous cell carcinoma developing in a diabetic foot ulcer. Int J Low Extrem Wounds 2011;10:101-3. 12. Misciali C, Dika E, Fanti PA, et al. Frequency of malignant neoplasms in 257 chronic leg ulcers. Dermatol Surg 2013;39:849-54. 13. Meaume S, Fromantin I, Teot L. Neoplastic wounds and degenerescence. J Tissue Viability 2013;22(4):122-30. 14. Tang JC, Vivas A, Rey A, Kirsner RS, Romanelli P. Atypical ulcers: wound biopsy results from a university wound pathology service. Ostomy Wound Manage 2012;58(6):20-22, 24, 26-29. 15. Dowsett C. Malignant fungating wounds: assessment and management. Br J Community Nurs 2002;7:394-400. 16. Senet P, Combemale P, Debure C, et al. Malignancy and chronic leg ulcers: the value of systematic wound biopsies: a prospective, multicenter, cross-sectional study. Arch Dermatol 2012;148:704-8.
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ADVANCES IN SKIN & WOUND CARE & JULY 2014
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