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Metastasizing eccrine porocarcinoma: report of a case and review of the literature
Metastasizing eccrine porocarcinoma: report of a case and review of the literature Pascale Huet, MD, a Michel Dandurand, MD, a Christine Pignodel, MD, b and Bernard Guillot, M D a Nfmes, France Eccrine porocarcinoma is a rare malignant tumor arising from the intraepidermal ductal portion of the eccfine sweat gland (acrosyringium). It usually affects older persons and is located most commonly on the lower extremities. We describe a 55-year-old man with an aggressive metastasizing eccrine porocarcinoma diagnosed 10 years after the primary lesion. The metastatic lesions were located in the pubic area and scrotum and were associated with progressive lymphedema. Several biopsy specimens revealed numerous rumor cells in the dermis and especially in the lumina of lymph and blood vessels. Immunohistochemical studies showed staining with cytokeratin KL1, epithelial membrane antigen, Ca 15-3, and Ca 19-9. Vimenfin, S-100 protein, neuron specific enolase, and carcino-embryonlc antigen were negative. Treatment with carbon dioxide laser failed. The use of interferon alfa-2a for 9 months stopped progression of the rumor. (J Am Acad Dermatol 1996;35:860-4.) Primary adenocarcinomas arising from the eccrine sweat glands are rare and represent approximately 0.005% of epithelial cutaneous neoplasms. 1 Eccrine porocarcinoma (EPC) is the most common varimat. 2 It originates from the intraepidermal ductal portion of the eccrine sweat gland (acrosyringium).3 The first two cases of EPC described were probably those of Smith and Coburn in 1956, 4, 5 but the first definite case was described by Pinkus and Mehregan in 1963. 6 The term eccrine porocarcinoma was introduced by Mishima and Morioka 7 in 1969 for the malignant counterpart of eccrine poroma. Since then, a few sporadic case reports and three large series of 27 cases (Shaw et al.8), 18 cases (Mehregan, Hashimoto, and Rahbarig), and 24 cases (Poiares-Baptista et al.l°), respectively, have been published. The incidence is difficult to estimate, ~1 but it occurred as approximately one case per 25,000 consecutive skin biopsy specimens received in a dermatopathology laboratory (18 cases per 450,000) 9, 12, 13 ORTI-tO
This article is made possible through an educational grant from the Dermatological Division, Ortho Pharmaceutical Corporation. From the Departments of Dermatologya and Anatomopathology,b University Hospital of Caremeau, Nimes. Reprint requests: Bernard Guillot, MD, Department of Dermatology, University Hospital of Caremeau, R. Debr6 avenue, 3000 N~nes, France. Copyright O 1996 by the American Academy of Dermatology, Inc. 0190-9622/96 $5.00 + 0 16/4/74380
860
We describe a case of EPC diagnosed 10 years after the initial lesion appeared. CASE REPORT A 55-year-old white man had widespread cutaneous metastases. He had a hyperkeratotic lesion on the right thigh in 1985, diagnosed as Bowen's disease and treated by cautery. In 1986 there was a local recurrence that was excised. In July 1991 a progressive lymphedema of the right thigh appeared. A computed tomographic scan of the abdomen did not show any abnormality. Lymphoscintigraphy confirmed the failure of lymphatic drainage. In April 1992 edema progressed to involve the entire fight lower limb. It was treated by transposition and autologous lymphatic grafts, but the treatment was unsuccessfial and was complicated by lympbedema of the left limb. In May 1993 a warty, ulcerated nodule appeared on the scrotum. A biopsy specimen revealed an infiltrating basal cell carcinoma. In April 1994 the patient noted numerous wellcircumscribed papules and infiltrated plaques in the pubic area (Fig. 1). Examination disclosed multiple fleshcolored or fight brown, firm tumors accompanied by an enormous lymphedema of the lower limbs and scrotum. No lymph node was palpable. Multiple biopsy specimens revealed numerous nests of anaplastic tumor cells in the dermis (Fig. 2). The lumina of dilated lymph and blood vessels were often plugged with tumor cells. The stroma contained an increased number of fibroblasts and occasionally appeared mucinous. The tumor cells invading the overlying epidermis formed solid intraepidermal aggregates. Larger aggregates of the manor cells formed ductlike lumina.
Journal of the American Academy of Dermatology Volume 35, Number 5, Part 2
Fig. 1. Numerous well-circumscribed papules and infiltrated plaques in pubic area, penis, and scrotum. Immunocytochemical studies led to the final diagnosis of cutaneous metastasizing EPC (Fig. 3). Tumor cells stained with the antibodies are shown in Table I. Reexamination of the initial lesion of the right thigh, excised in 1985, revealed an EPC with local recurrence in 1986. No visceral metastases were found. A trial of carbon dioxide laser treatment failed. During the next months there was gradual progression of the cutaneous metastases extending to the genitals. A treatment with interferon alfa-2a (Roferon), 9 million units 3 days per week, and isotretinoin, 2 mg/kg daily, was started. Two months later, isotreOnoinwas stopped and treatment with interferon was continued. After 9 months, the progression was stopped and lesions began to clear.
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Fig. 2. Biopsy specimen showing well-demarcated nests of anaplastic tumor cells in dermis, invading overlying epidermis and plugging some vessels. (Hematoxylin-eosin stain; original magnification xl0.)
Fig. 3. Staining of tumor cells with antibody to Ca 15-3. (Original magnification xl0.)
DISCUSSION EPC most commonly affects elderly persons) ° The average age is 67.5 years n with a range of 19 to 94 years. 14' 15 The sex incidence is contested) 6 A variable but often lengthy duration is typical and ranges from 2 months to 50 years,9' 14 suggesting the possibility of malignant change in a preexisting benign lesion. 6, 17-al In contrast to benign eccrine poroma, the location of its malignant counterpart is not correlated with the highest concentration of eccrine sweat glands (palmoplantar areas). 11 The main localizations include the lower limbs (55%, especially legs), followed by the head (nose, forehead, cheeks) and scalp (20%), then the upper limbs (12%), and the mink and the abdomen (10%). 2 Other localizations such as the nailbed have rarely been reported. 22, 23 EPC can appear as a nodule or a verrucous, dome-shaped, cauliflowerlike, infiltrated or erosive plaque or as a polypoid growth that is frequently ulcerated. Multinodularity, ulceration, and rapid
growth may be associated with either locally recurrent or metastatic disease. 24 In one patient, it had a zosteriform appearance. 16 Although often red, the lesion can also be light brown or flesh-colored. The size of the primary lesion averages 2.4 cm, with a range of about 1 to 10 cm. 13 A peculiar mode of presentation is dissemination of numerous cutaneous nodules in a fashion suggesting a lymphatic spread.5, 6, 25 The clinical differential diagnosis includes many other neoplasms 11 such as seborrheic keratosis,% w a r t y pyogenic granuloma, fibroma, or nevus, as well as basal cell carcinoma, squamous cell carcinoma, Bowen's disease, and amelanotic melanoma. 8 Approximately 20% of EPCs recur locally from 4 months to 12 years after removal. 9 Another 20% metastasize to regional lymph nodes; these patients have a high mortality rate (67% in the series of Snow and Reiznes). 11 Multiple cutaneous metastases can
Journal of the American Academy of Dermatology
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November 1996
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Table I. Immunocytochemical studies Antibody
Staining
Laboratory
Cytokeratin protein KL1 Epithelial membrane antigen (EMA) CA 15-3 CA 19-9 Vimentin S-100 protein H M 45 Neuron specific enolase (NSE) Carcino-embryonic antigen (CEA)
+ + + + _+ (some secretory granules)
Immuno-Teck Dako Cis Bio International Cis Bio International Dako Dako Immtmo-Teck Dako Dako
also develop. 11, 27 EPC may produce lymphangitis ca_rcinomatosa associated with lymphedema 6, 9, 28, 29 as in our patient. Lymphatic involvement can also explain the regional, intraepidermal, or satellite minor masses that may involve the entire leg, abdomen, or anogenital region, 1 as in our patient. Less commonly, patients exhibit visceral metastases including lung, 5, 18 retroperitoneum,5 long bones, is' 30 breast, 31 liver, 26 mediastinum, 26 urinary bladder, 26 peritoneum, 26 or ovary. 31 The histopathologic features of EPC are characteristic. 32 The tumor arises from terminal cells of the intraepidermal portion of the eccrine sweat duct, or acrosyringium. It can extend from the surface epidermis to various levels of the dermis] 8 and occasionally involves the subcutaneous fat. 9 It invades dermal lymphatics, spreads within them, and finally reinvades the epidermis. 7 This particular process of metastatic spread explains the extensive dissemination of cutaneous metastases within a circumscribed skin region and the late occurrence of internal metastases. An outstanding histopathologic feature observed in our patient is the epidermotropism of the metastatic carcinoma cells. 5-8 The intraepidermal portion is comprised of many well-defined nests of small anaplastic minor cells. The nests range in size from large masses to individual cells mimicking Paget's cells. A striking finding is the presence of plugs of tumor cells within superficial lymphatic vessels. Individual cells have a regular, vesicular, hyperchromatic, pleomorphic nucleus, and an abundant clear cytoplasm. In some cases, variable amounts of glycogen contained in granules are seen in the cytoplasm of tumor cells, as was the case in our patient. Another histologic feature of EPC is the presence in the tumor masses of many ductlike lumina.
Electron microscopy 33-36 is of little interest. Immunohistochemical studies of EPCs have been infrequent, but may be helpful in the differential diagnosis 37-4° (Table I). The differential diagnosis includes a variety of benign and malignant tumors. The intraepidermal phase must be distinguished from hidroacanthoma simplex, Bowen's disease, 11 and Paget's disease, is In the invasive phase, squamous cell carcinoma with acantholysis and basal cell carcinoma should be excluded. Superficial spreading malignant melanoma may be also suggested. A difficult differential diagnostic dilemma is posed by epidermotropic metastatic adenocarcinoma. Only careful evaluation with adequate clinical information and immunohistochemical stainings will allow the correct diagnosis to be made. 13 The prognosis of EPC remains difficuk to assess. Tumors present for only a few weeks can be accompartied by both regional and visceral metastases, whereas others can be present up to 30 years with neither. A mortality rate cannot be determined with certainty. According to available information, most patients with metastases died despite treatment. 36 Because of the propensity to develop local recurrences, wide local excision of the primary tumor with histologic confirmation of tumor-free margins is the treatment of choice. 41 Prophylactic lymphadenectomy should be done if regional nodes are enlarged 14 or when a recurrent or poorly differentiated tumor with intralymphatic permeation is present. TM42 Once the tumor has metastasized, the outlook is poor. Radiotherapy 4245 and systemic chemotherapy46, 47 seem of uncertain benefit. Superficial irradiation with hypert_hermia is a promising alternative. 25 Retinoids 4851 were shown to have some benefit in one patient 52 but failed in another. 53 Dummer et al.54
Journal of the American Academy of Dermatology Volume 35, Number 5, Part 2
reported the successful treatment of three cutaneous metastases with perilesional interferon alfa in combination with interleukin 2. In view of the experience of Lippman et al.,55 who treated advanced squamous cell carcinoma of the skin with 13-cis-retinoic acid and interferon alfa-2a, we used this combination in our patient. Isotretinoin had to be discontinued because of intolerance, but after 9 months, interferon therapy alone seemed to stop progression of the tumor. REFERENCES 1. Wick MR, Coffin MC. Adnexal carcinomas of the skin, I. Eccrine carcinomas. Cancer 1985;56:1147-62. 2. Moulonguet-MichanI, Civatte J. Carcinomes annexiels. In Dubertret L, ed. Cancers cutan6s. Flammarion M6d. Sciences 1992:205-6. 3. Baril A, Claudy A, Boucheron S, et al. Le carcinome eccrine 6pidermotrope: h propos d'une observation avec 6tude ullra-structurale. Ann Pathol 1984;4:203-9. 4. Smith JLS, Coburn JG. Hidroacanthoma simplex: assessment of selected group of intraepidermal basal cell epitheliomata and their malignant homologues. Br J Dermatol 1956;68:400-18. 5. Grosshans E, Vetter JM, Capesius C. Poromes eccrines malins, porodpithdliomes, porocarcinomes. Ann Anat Pathol 1975;20:382-94. 6. Pinkus H, Mehregan Ah. Epidermotropic eccrine carcinoma: a case combining features of eccrine poroma and Paget's dermatosis. Arch Dermatol 1963;88:597-607. 7. Mishima Y, Morioka S. Oncogenic differentiation of the intraepidermal eccrine sweat duct: eccrine poroma, poroepithelioma, and porocarcinoma. Dermatologica 1969; 138:238-50. 8. Shaw M, McKee PH, Lowe D, et al. Malignant eccrine poroma: a study of twenty-seven cases. Br J Dermatol 1982;107:675-80. 9. Mehregan AH, Hashimoto K, Rahbari H. Eccrine adenocarcinoma: clinicopathological study of 35 cases. Arch Dermatol 1983;119:104-14. 10. Poiares-Baptista A, Tellechea O, Reis JP, et al. Porocarcinome eccrine: revue de 24 cas. Ann Dermatol Venereol 1993;120:107-15. 11. Snow SN, Reizner GT. Eccrine porocarcinoma of the face. J Am Acad Dermatol 1992;27:306-11. 12. Labbe D, Harbon S, Dompmartin A, et al. Les poromes eccrines matins: ~t propos de deux localisations faciales. Ann Chit Plast Esth6t 1989;34:146-52. 13. Santa Cruz DJ. Sweat gland carcinomas: a comprehensive review. Semin Diagn Pathol 1987;4:38-74. 14. Goedde TA, Bumpers H, Fiscella J, et al. Eccrine porocarcinoma. J Surg Oncol 1994;55:261-4. 15. Landa NG, Winkelmann RK. Epidermotropic eccfine porocarcinoma. J Am Acad Dermatol 1991;24:27-31. 16. Aldyoshi E, Nogita T, Yamaguchi R, et al. Eccrine porocarcinoma. Dermatologica 1991; 182:239-42. 17. Zina AM, Bundino S, Pippione MG. Pigmented hidroacanthoma simplex with porocarcinoma. J Cutan Pathol 1982;9:104-12. 18. Gschnaidt F, Horn F, Lindlbauer R, et al. Eccrine porocarcinoma. J Cutan Pathol 1980;7:349-53. 19. Bardach H. Hidroacanthoma simplex with in situ porocarcinoma. J Cutan Pathol 1978;5:236-48.
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20. Moreno A, Salvatella N, Guix M, et al. Malignant hidroacanthoma simplex: a light microscopic, ultrastructural, and immuno-histochemicalstudy of 2 cases. Dermatologica 1984;169:161-6. 21. Kitamura K, Kinehara M, Tamura N, et al. Hidroacanthoma simplex with invasive growth. Curls 1983;32:83-8. 22. Requena L, Sanchez M, Aguilar A, et al. Periungueal porocarcinoma. Dermatologica 1990;180:177-80. 23. Van Gorp J, Van der Putte SCJ. Periungueal eccrine porocarcinoma. Dermatology 1993;187:67-70. 24. Ruffieux C, Ramelet AA. Porocarcinome eccrine: pr6sentarlon de 4 cas. Dermatologica 1985;170:202-6. 25. Turner JJ, Maxwell L, Bursle GA. Eccrine porocarcinoma: a case report with light microscopy and ultrastmcture. Pathology 1982;14:469-75. 26. De Kort WJA. Eccrine porocarcinoma. Br J Dermatol 1985;112:227-9. 27. Matloub HS, Ctmningharn MW, Yousif NJ, et al. Eccrine porocarcinoma. Ann Plast 1988;20:351-5. 28. Bottles K, Sagebiel RW, McNutt NS. Malignant eccrine poroma: case report and review of the literature. Cancer 1984;53:1579-85. 29. Schmutz JL, Cuny JF, ChemidlingM, et al. Porocarcinome eccrine. Ann Dermatol Venereol 1989;116:858-60. 30. Grober A, Goldberg I, Rotem A. Malignanteccfine poroma with metastatic involvementof the long bones. Clin Orthop 1987;223:303-7. 31. Krinitz K. Malignes intraepidermales ekkrines porom. Z Haut-GeschlKrankh 1972;47:9-17. 32. Biaunie G, Picot R, Salagnac V, et al. Porocarcinome eccrine: h propos d'un cas. Jottm6es dermatologiques de Paris, Mars 1988. 33. Vilmer C, Le Doussal V, Texier J, et al. Poromes eccrines matins: 6tude de deux cas avec examen ultrastmcmral. Ann Dermatol Venereol 1985; 112:67-71. 34. Kolde G, Macher E. Metastasizing eccrine porocarcinoma: report of two cases with fatal outcome. Pathol Res Pract 1991;187:477-81. 35. Hashimoto K, Gross BG, Lever WF. The ultrastructure of the skin of human embryos: I. The intraepidermal eccfine sweat duct. J Invest Dermatol 1965;45:139-51. 36. Pierard-Franchimont C, Reginster M, Arrese JE, et al. Evolution fatale d'un porocarcinome. Nouv Dermatol 1994;13:101-4. 37. Puttick L, Ince P, Comaish JS. Three cases of eccrine porocarcinoma. Br J Dermatol 1986; 115:111-6. 38. Penneys NS, Nadji M, Ziegels-WeissmanJ, et al. Carcin0embryonic antigen in sweat gland carcinomas. Cancer 1982;50:1608-11. 39. Swanson PE, Cherwitz DL, Nettmann MP, et al. Eccrine sweat gland carcinoma: an histologic and immunohistochemical study of 32 cases. J Cutan Pathol 1987;14:65-86. 40. Takanashi M, Urabe A, Nakayarna J, et al. Distribution of epithelial membrane antigen in eccrine poroma. Dermatologica 1991;183:187-90. 41. Pemia LR, Guzman-SteinG, Miller HL. Surgical treatment of an aggressive metastasized eccfine poroma. Ann Plast Surg 1993;30:257-9. 42. E1 Domeiri AA, Brasfield RD, Huvos AG, et al. Sweat gland carcinoma: clinicopathologic study of 83 patients. Ann Surg 1971;173:270-4. 43. Langfritz K, Grabbe S, Kovacs G, et al. Metastasierendes ekkrines porokarzinom. Hautarzt 1993;44:176-9. 44. Whittington R, Browning ME, Farrell GR, et al. Radiation therapy and chemotherapy in malignant sweat gland minors. J Am Acad Dermatol 1986;15:1093-7.
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45. Harari PM, Shimm DS, Bangert JL, et al. The role of radiotherapy in the treatment of malignant sweat gland neoplasms. Cancer 1990;65:1737-40. 46. Coonley CJ, Kelsen DP, Huvos AG, et al. Chemotherapy of metastatic sweat gland carcinoma. Am J Clin Oncol 1985;8:307-11. 47. Briscoe KE, Grage T, Kennedy BJ. Sustained complete remission of metastatic sweat gland carcinoma following regional hyperthermic perfusion. JAMA 1978;240:51-2. 48. Hughes BR, Marks R, Pearse AD, et al. Clinical response and tissue effects of etretinate treatment of patients with solar keratoses and basal cell carcinoma. J Am Acad Dermatol 1988;18:522-9. 49. Meyskens FL Jr, Gilmartin E, Alberts DS, et al. Activity of isotretinoin against squamous cell cancers and preneoplastic lesions. Cancer Treat Rep 1982;66:1315-8. 50. Lippman SM, Meyskens FL Jr. Treatment of advanced
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squamous cell carcinoma of the skin with isotretinoin. Ann Intern Med 1987;107:499-501. Levine N, Meyskens FL. Topical vitamin-A-acid therapy for cutaneous metastatic melanoma. Lancet 1980;2: 224-6. Roach M. A malignant eccrine poroma responds to isotretinoin (13-cis-retinoic acid). Ann Intern Med 1983;99: 486-8. Friedland M, Bajracharya A, Arlin Z. Malignant eccrine poroma and isotretinoin. Ann Intern Med 1984;100:614. Dummer R, Becker JC, Boser B, et al. Successful therapy of metastatic eccfine poroma using perilesional interferon alfa and interleukin 2. Arch Dermatol 1992;128:1127-8. Lippman SM, Parkinson DR, Itri LM, et al. 13-cis-retinoic acid and interferon alpha-2a: effective combinationtherapy for advanced squamous cell carcinoma of the skin. J Natl Cancer Inst 1992;84:235-41.
This article is made possible through an educational grant from the Dermatological Division, Ortho Pharmaceutical Corporation. From the Departments of Dermatologya and Anatomopathology,b University Hospital of Caremeau, Nimes. Reprint requests: Bernard Guillot, MD, Department of Dermatology, University Hospital of Caremeau, R. Debr6 avenue, 3000 N~nes, France. Copyright O 1996 by the American Academy of Dermatology, Inc. 0190-9622/96 $5.00 + 0 16/4/74380
860
We describe a case of EPC diagnosed 10 years after the initial lesion appeared. CASE REPORT A 55-year-old white man had widespread cutaneous metastases. He had a hyperkeratotic lesion on the right thigh in 1985, diagnosed as Bowen's disease and treated by cautery. In 1986 there was a local recurrence that was excised. In July 1991 a progressive lymphedema of the right thigh appeared. A computed tomographic scan of the abdomen did not show any abnormality. Lymphoscintigraphy confirmed the failure of lymphatic drainage. In April 1992 edema progressed to involve the entire fight lower limb. It was treated by transposition and autologous lymphatic grafts, but the treatment was unsuccessfial and was complicated by lympbedema of the left limb. In May 1993 a warty, ulcerated nodule appeared on the scrotum. A biopsy specimen revealed an infiltrating basal cell carcinoma. In April 1994 the patient noted numerous wellcircumscribed papules and infiltrated plaques in the pubic area (Fig. 1). Examination disclosed multiple fleshcolored or fight brown, firm tumors accompanied by an enormous lymphedema of the lower limbs and scrotum. No lymph node was palpable. Multiple biopsy specimens revealed numerous nests of anaplastic tumor cells in the dermis (Fig. 2). The lumina of dilated lymph and blood vessels were often plugged with tumor cells. The stroma contained an increased number of fibroblasts and occasionally appeared mucinous. The tumor cells invading the overlying epidermis formed solid intraepidermal aggregates. Larger aggregates of the manor cells formed ductlike lumina.
Journal of the American Academy of Dermatology Volume 35, Number 5, Part 2
Fig. 1. Numerous well-circumscribed papules and infiltrated plaques in pubic area, penis, and scrotum. Immunocytochemical studies led to the final diagnosis of cutaneous metastasizing EPC (Fig. 3). Tumor cells stained with the antibodies are shown in Table I. Reexamination of the initial lesion of the right thigh, excised in 1985, revealed an EPC with local recurrence in 1986. No visceral metastases were found. A trial of carbon dioxide laser treatment failed. During the next months there was gradual progression of the cutaneous metastases extending to the genitals. A treatment with interferon alfa-2a (Roferon), 9 million units 3 days per week, and isotretinoin, 2 mg/kg daily, was started. Two months later, isotreOnoinwas stopped and treatment with interferon was continued. After 9 months, the progression was stopped and lesions began to clear.
H u e t et al.
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Fig. 2. Biopsy specimen showing well-demarcated nests of anaplastic tumor cells in dermis, invading overlying epidermis and plugging some vessels. (Hematoxylin-eosin stain; original magnification xl0.)
Fig. 3. Staining of tumor cells with antibody to Ca 15-3. (Original magnification xl0.)
DISCUSSION EPC most commonly affects elderly persons) ° The average age is 67.5 years n with a range of 19 to 94 years. 14' 15 The sex incidence is contested) 6 A variable but often lengthy duration is typical and ranges from 2 months to 50 years,9' 14 suggesting the possibility of malignant change in a preexisting benign lesion. 6, 17-al In contrast to benign eccrine poroma, the location of its malignant counterpart is not correlated with the highest concentration of eccrine sweat glands (palmoplantar areas). 11 The main localizations include the lower limbs (55%, especially legs), followed by the head (nose, forehead, cheeks) and scalp (20%), then the upper limbs (12%), and the mink and the abdomen (10%). 2 Other localizations such as the nailbed have rarely been reported. 22, 23 EPC can appear as a nodule or a verrucous, dome-shaped, cauliflowerlike, infiltrated or erosive plaque or as a polypoid growth that is frequently ulcerated. Multinodularity, ulceration, and rapid
growth may be associated with either locally recurrent or metastatic disease. 24 In one patient, it had a zosteriform appearance. 16 Although often red, the lesion can also be light brown or flesh-colored. The size of the primary lesion averages 2.4 cm, with a range of about 1 to 10 cm. 13 A peculiar mode of presentation is dissemination of numerous cutaneous nodules in a fashion suggesting a lymphatic spread.5, 6, 25 The clinical differential diagnosis includes many other neoplasms 11 such as seborrheic keratosis,% w a r t y pyogenic granuloma, fibroma, or nevus, as well as basal cell carcinoma, squamous cell carcinoma, Bowen's disease, and amelanotic melanoma. 8 Approximately 20% of EPCs recur locally from 4 months to 12 years after removal. 9 Another 20% metastasize to regional lymph nodes; these patients have a high mortality rate (67% in the series of Snow and Reiznes). 11 Multiple cutaneous metastases can
Journal of the American Academy of Dermatology
862
November 1996
Huet et aL
Table I. Immunocytochemical studies Antibody
Staining
Laboratory
Cytokeratin protein KL1 Epithelial membrane antigen (EMA) CA 15-3 CA 19-9 Vimentin S-100 protein H M 45 Neuron specific enolase (NSE) Carcino-embryonic antigen (CEA)
+ + + + _+ (some secretory granules)
Immuno-Teck Dako Cis Bio International Cis Bio International Dako Dako Immtmo-Teck Dako Dako
also develop. 11, 27 EPC may produce lymphangitis ca_rcinomatosa associated with lymphedema 6, 9, 28, 29 as in our patient. Lymphatic involvement can also explain the regional, intraepidermal, or satellite minor masses that may involve the entire leg, abdomen, or anogenital region, 1 as in our patient. Less commonly, patients exhibit visceral metastases including lung, 5, 18 retroperitoneum,5 long bones, is' 30 breast, 31 liver, 26 mediastinum, 26 urinary bladder, 26 peritoneum, 26 or ovary. 31 The histopathologic features of EPC are characteristic. 32 The tumor arises from terminal cells of the intraepidermal portion of the eccrine sweat duct, or acrosyringium. It can extend from the surface epidermis to various levels of the dermis] 8 and occasionally involves the subcutaneous fat. 9 It invades dermal lymphatics, spreads within them, and finally reinvades the epidermis. 7 This particular process of metastatic spread explains the extensive dissemination of cutaneous metastases within a circumscribed skin region and the late occurrence of internal metastases. An outstanding histopathologic feature observed in our patient is the epidermotropism of the metastatic carcinoma cells. 5-8 The intraepidermal portion is comprised of many well-defined nests of small anaplastic minor cells. The nests range in size from large masses to individual cells mimicking Paget's cells. A striking finding is the presence of plugs of tumor cells within superficial lymphatic vessels. Individual cells have a regular, vesicular, hyperchromatic, pleomorphic nucleus, and an abundant clear cytoplasm. In some cases, variable amounts of glycogen contained in granules are seen in the cytoplasm of tumor cells, as was the case in our patient. Another histologic feature of EPC is the presence in the tumor masses of many ductlike lumina.
Electron microscopy 33-36 is of little interest. Immunohistochemical studies of EPCs have been infrequent, but may be helpful in the differential diagnosis 37-4° (Table I). The differential diagnosis includes a variety of benign and malignant tumors. The intraepidermal phase must be distinguished from hidroacanthoma simplex, Bowen's disease, 11 and Paget's disease, is In the invasive phase, squamous cell carcinoma with acantholysis and basal cell carcinoma should be excluded. Superficial spreading malignant melanoma may be also suggested. A difficult differential diagnostic dilemma is posed by epidermotropic metastatic adenocarcinoma. Only careful evaluation with adequate clinical information and immunohistochemical stainings will allow the correct diagnosis to be made. 13 The prognosis of EPC remains difficuk to assess. Tumors present for only a few weeks can be accompartied by both regional and visceral metastases, whereas others can be present up to 30 years with neither. A mortality rate cannot be determined with certainty. According to available information, most patients with metastases died despite treatment. 36 Because of the propensity to develop local recurrences, wide local excision of the primary tumor with histologic confirmation of tumor-free margins is the treatment of choice. 41 Prophylactic lymphadenectomy should be done if regional nodes are enlarged 14 or when a recurrent or poorly differentiated tumor with intralymphatic permeation is present. TM42 Once the tumor has metastasized, the outlook is poor. Radiotherapy 4245 and systemic chemotherapy46, 47 seem of uncertain benefit. Superficial irradiation with hypert_hermia is a promising alternative. 25 Retinoids 4851 were shown to have some benefit in one patient 52 but failed in another. 53 Dummer et al.54
Journal of the American Academy of Dermatology Volume 35, Number 5, Part 2
reported the successful treatment of three cutaneous metastases with perilesional interferon alfa in combination with interleukin 2. In view of the experience of Lippman et al.,55 who treated advanced squamous cell carcinoma of the skin with 13-cis-retinoic acid and interferon alfa-2a, we used this combination in our patient. Isotretinoin had to be discontinued because of intolerance, but after 9 months, interferon therapy alone seemed to stop progression of the tumor. REFERENCES 1. Wick MR, Coffin MC. Adnexal carcinomas of the skin, I. Eccrine carcinomas. Cancer 1985;56:1147-62. 2. Moulonguet-MichanI, Civatte J. Carcinomes annexiels. In Dubertret L, ed. Cancers cutan6s. Flammarion M6d. Sciences 1992:205-6. 3. Baril A, Claudy A, Boucheron S, et al. Le carcinome eccrine 6pidermotrope: h propos d'une observation avec 6tude ullra-structurale. Ann Pathol 1984;4:203-9. 4. Smith JLS, Coburn JG. Hidroacanthoma simplex: assessment of selected group of intraepidermal basal cell epitheliomata and their malignant homologues. Br J Dermatol 1956;68:400-18. 5. Grosshans E, Vetter JM, Capesius C. Poromes eccrines malins, porodpithdliomes, porocarcinomes. Ann Anat Pathol 1975;20:382-94. 6. Pinkus H, Mehregan Ah. Epidermotropic eccrine carcinoma: a case combining features of eccrine poroma and Paget's dermatosis. Arch Dermatol 1963;88:597-607. 7. Mishima Y, Morioka S. Oncogenic differentiation of the intraepidermal eccrine sweat duct: eccrine poroma, poroepithelioma, and porocarcinoma. Dermatologica 1969; 138:238-50. 8. Shaw M, McKee PH, Lowe D, et al. Malignant eccrine poroma: a study of twenty-seven cases. Br J Dermatol 1982;107:675-80. 9. Mehregan AH, Hashimoto K, Rahbari H. Eccrine adenocarcinoma: clinicopathological study of 35 cases. Arch Dermatol 1983;119:104-14. 10. Poiares-Baptista A, Tellechea O, Reis JP, et al. Porocarcinome eccrine: revue de 24 cas. Ann Dermatol Venereol 1993;120:107-15. 11. Snow SN, Reizner GT. Eccrine porocarcinoma of the face. J Am Acad Dermatol 1992;27:306-11. 12. Labbe D, Harbon S, Dompmartin A, et al. Les poromes eccrines matins: ~t propos de deux localisations faciales. Ann Chit Plast Esth6t 1989;34:146-52. 13. Santa Cruz DJ. Sweat gland carcinomas: a comprehensive review. Semin Diagn Pathol 1987;4:38-74. 14. Goedde TA, Bumpers H, Fiscella J, et al. Eccrine porocarcinoma. J Surg Oncol 1994;55:261-4. 15. Landa NG, Winkelmann RK. Epidermotropic eccfine porocarcinoma. J Am Acad Dermatol 1991;24:27-31. 16. Aldyoshi E, Nogita T, Yamaguchi R, et al. Eccrine porocarcinoma. Dermatologica 1991; 182:239-42. 17. Zina AM, Bundino S, Pippione MG. Pigmented hidroacanthoma simplex with porocarcinoma. J Cutan Pathol 1982;9:104-12. 18. Gschnaidt F, Horn F, Lindlbauer R, et al. Eccrine porocarcinoma. J Cutan Pathol 1980;7:349-53. 19. Bardach H. Hidroacanthoma simplex with in situ porocarcinoma. J Cutan Pathol 1978;5:236-48.
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