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Dermatologic Care in the Homeless and Underserved Populations: Observations From the Venice Family Clinic
Acquired Perforating Dermatosis Associated With Primary Biliary Cirrhosis and Hashimoto Thyroiditis
Acquired perforating dermatosis (APD) is an uncommon skin eruption of unclear etiology that most often is associated with diabetes mellitus or chronic renal insufficiency. There are rare reports of APD in association with liver disease or thyroid disease. We report a case of APD in a patient with both primary biliary cirrhosis and Hashimoto thyroiditis in the absence of diabetes mellitus and chronic renal insufficiency. The patient had a partial response to narrowband UVB phototherapy.
Case Report
A 47-year-old woman with a history of primary biliary cirrhosis and rheumatoid arthritis presented with a skin eruption of 4 years' duration. The patient stated that her skin felt pruritic overall, but the lesions had a painful quality. She could not identify any exacerbating or remitting factors. Her medications included prednisone 5 mg daily for rheumatoid arthritis and occasional propoxyphene for pain and zolpidem tartrate for insomnia. She had no personal or family history of diabetes mellitus, renal insufficiency, or similar skin disorders. On physical examination, the patient demonstrated mild scleral icterus. Her skin had a diffuse eruption of erythematous hyperkeratotic papules over the trunk and extremities. Several of these papules appeared excoriated and others appeared to have a central hyperkeratotic crust and hyperpigmented scarring (Figure 1).
Laboratory studies disclosed the following values: alanine aminotransferase, 122 U/L (reference range, 5–50 U/L); aspartate aminotransferase, 95 U/L (reference range, 15–50 U/L); alkaline phosphatase, 603 U/L (reference range, 35–110 U/L); total bilirubin, 6.4 mg/dL (reference range, 0.2–1.5 mg/dL); serum creatinine, 0.6 mg/dL (reference range, 0.7–1.2 mg/dL); and hemoglobin A1c, 4.2% (reference range, 4.4%–5.9%). The patient had a positive antinuclear antibody titer of 1:80 (reference range, <1:40) in a homogenous staining pattern. Her viral hepatitis infection serologies and antismooth muscle antibody titers were all negative. Additionally, her antimitochondrial antibody titers were positive, 1:160 (reference range, <1:20); thyrotropin levels were increased, 10.3 mIU/L (reference range, 0.3–4.7 mIU/L); and thyroid peroxidase antibodies were elevated, 14.8 IU/mL (reference range, <2.0 IU/mL).
Results of a liver biopsy demonstrated biliary injury and loss, with bridging fibrosis, consistent with stage III primary biliary cirrhosis. Results of a skin punch biopsy were remarkable for hyperkeratosis, epidermal acanthosis, and a channel filled with neutrophils and both eosinophilic and basophilic staining debris traversing the epidermis (Figure 2). A chronic infiltrate of lymphocytes, histiocytes, and neutrophils was present at the base of the transepidermal channel. Results of a Masson trichrome stain did not demonstrate substantial amounts of collagen; results of an acid orcein stain showed some elastin fibers at the base of the transepidermal channel (Figures 3 and 4). This combination of clinical and histopathologic findings was consistent with acquired perforating dermatosis (APD).
In addition to starting thyroid hormone replacement therapy for Hashimoto thyroiditis, the patient began narrowband UVB treatments 3 times weekly for her skin condition. After several months of thyroid hormone replacement therapy and 60 narrowband UVB treatments that led to normalization of her thyrotropin levels, the patient noted no new lesions, though the resolution of her old lesions was not substantial.
Comment
APD, often thought to be synonymous with acquired reactive perforating collagenosis, is a skin condition that is usually associated with pruritus and characterized by umbilicated papules and nodules with a central adherent plug. These nodules are manifestations of transepidermal elimination of ill-defined material containing cellular debris, elastin, and collagen. The nosology of perforating dermatoses has been complicated by considerable overlap among the different entities. It generally is accepted that APD is differentiated from other primary perforating dermatoses by the presence of an underlying systemic disease.In contradistinction to the primary perforating disorders Kyrle disease, reactive perforating collagenosis, elastosis perforans serpiginosa, and perforating folliculitis, APD characteristically is associated with diabetes mellitus, chronic renal insufficiency, or both, and does not display a familial inheritance pattern.1 Up to 11% (8/72) of patients who received hemodialysis have been reported to have APD.2 There also have been case reports of APD in association with atopic dermatitis,3 scabies infestation,4,5 herpes zoster,6-8 human immunodeficiency virus,9 pulmonary fibrosis,10 thyroid disease,11 and liver disease.12-17
In contrast to associations between APD and diabetes mellitus or renal disease, associations between APD and liver disease are reported less frequently. Kahana et al12 reported 2 cases of perforating folliculitis associated with primary sclerosing cholangitis. Salomon et al13 reported a case of a 46-year-old man with alcoholic liver disease who subsequently developed a perforating dermatosis. Lee et al14 reported a case of a 69-year-old man with hepatitis B and hepatocellular carcinoma who developed APD. Tang et al15 reported a case of a 33-year-old man with diabetes mellitus and hepatitis B who developed APD. Faver et al11 reported a case of a 71-year-old man with “liver dysfunction” and nephropathy and a case of a 54-year-old woman with diabetes mellitus and “chronic active hepatitis,” both with APD. Skiba et al16 reported a case of a 33-year-old woman with diabetes mellitus and sclerosing cholangitis who also developed APD. Fujimoto et al17 reported 2 cases of APD with liver disease—one patient was a 50-year-old man with unspecified hepatitis, and the other patient was a 75-year-old man with diabetes mellitus and a hepatoma.
Reports of associations between APD and thyroid disease are even more infrequent than reports of APD and liver disease. Faver et al11 reported 3 cases of APD associated with hypothyroidism; 2 of these patients had concomitant diabetes mellitus. Although reports of associations between APD and thyroid disease are rare, it is unclear if this is because of a true rarity of coincidence or because the thyroid status of these patients typically is not checked or reported.
The pathogenesis of APD is unknown. The prominent association of APD with the symptom of pruritus has led many authors to speculate on a connection between scratching, trauma, and APD.3,18 Some studies have demonstrated increased expression of the 67-kD elastin receptor in lesions of perforating dermatoses; however, this expression is not uniformly elevated and the significance of this expression is not known.17 Other studies have found elevated levels of the extracellular matrix protein fibronectin in lesions of APD, but similar to the elastin receptor findings, the significance of this observation is unknown.19,20
Histopathologically, lesions of APD are characterized by acanthosis and focal vacuolar alteration in the basal epidermis, with an associated underlying mixed infiltrate of lymphocytes, macrophages, neutrophils, and occasional mast cells. A transepidermal canal can be identified that often contains parakeratotic keratin, degenerated inflammatory cells, elastin, and collagen. The elastin and collagen in these lesions appear normal ultrastructurally, and results of direct immunofluorescence studies are negative.21,22 In one study of APD associated with diabetes mellitus and renal insufficiency, needlelike crystals with some degree of calcification were identified. They were postulated to be uric acid or calcium hydroxyapatite crystals.23
Treatment of APD has proven to be challenging. Some clinicians report improvement of APD with topical retinoids19,24,25; topical, intralesional, or systemic corticosteroids26; oral doxycycline27; oral thalidomide9; oral allopurinol28; psoralen plus UVA phototherapy29; and broadband UVB phototherapy.11,30 Reports of narrowband UVB phototherapy in the treatment of APD appear promising.31,32 Ohe et al33 reported a case series of 5 patients with APD; all patients responded to narrowband UVB phototherapy.
- Rapini RP, Hebert AA, Drucker CR. Acquired perforating dermatosis: evidence for combined transepidermal elimination of both collagen and elastic fibers. Arch Dermatol. 1989;125:1074-1078.
- Morton CA, Henderson IS, Jones MC, et al. Acquired perforating dermatosis in a British dialysis population. Br J Dermatol. 1996;135:671-677.
- Thiele-Ochel S, Schneider LA, Reinhold K, et al. Acquired perforating dermatosis: is it due to damage by scratching? Br J Dermatol. 2001;145:173-174.
- Hinrichs W, Breuckmann F, Altmeyer P, et al. Acquired perforating dermatosis: a report on 4 cases associated with scabies infection. J Am Acad Dermatol. 2004;51:665-667.
- Kurschat P, Kroger A, Scharffetter-Kochanek K, et al. Acquired reactive perforating collagenosis triggered by scabies infection. Acta Derm Venereol. 2000;80:384-385.
- Bang SW, Kim YK, Whang KU. Acquired reactive perforating collagenosis: unilateral umbilicated papules along the lesions of herpes zoster. J Am Acad Dermatol. 1997;36:778-779.
- Lee HN, Lee DW, Lee JY, et al. Two cases of reactive perforating collagenosis arising at the site of healed herpes zoster. Int J Dermatol. 2001;40:191-192.
- Zanardo L, Stolz W, Landthaler M, et al. Reactive perforating collagenosis after disseminated zoster. Dermatology. 2001;203:273-275.
- Rubio FA, Herranz P, Robayna G, et al. Perforating folliculitis: report of a case in an HIV-infected man. J Am Acad Dermatol. 1999;40:300-302.
- Tsuboi H, Mukuno A, Sato N, et al. Acquired reactive perforating collagenosis in a patient with lung fibrosis. J Dermatol. 2004;31:916-919.
- Faver IR, Daoud MS, Su WP. Acquired reactive perforating collagenosis. report of six cases and review of the literature. J Am Acad Dermatol. 1994;30:575-580.
- Kahana M, Schewach-Millet M, Trau H, et al. Perforating folliculitis in association with primary sclerosing cholangitis. Am J Dermatopathol. 1985;7:271-276.
- Salomon RJ, Baden TJ, Gammon WR. Kyrle's disease and hepatic insufficiency. Arch Dermatol. 1986;122:18-19.
- Lee YS, Vijayasingam S, Tan YO, et al. Acquired perforating dermatosis associated with recurrent hepatocellular carcinoma. Int J Dermatol. 1996;35:743-745.
- Tang WY, Chong LY, Lam SY, et al. Acquired reactive perforating collagenosis in two Chinese patients. Int J Dermatol. 1995;34:196-198.
- Skiba G, Milkiewicz P, Mutimer D, et al. Successful treatment of acquired perforating dermatosis with rifampicin in an Asian patient with sclerosing cholangitis. Liver. 1999;19:160-163.
- Fujimoto N, Akagi A, Tajima S, et al. Expression of the 67-kDa elastin receptor in perforating skin disorders. Br J Dermatol. 2002;146:74-79.
- Hong SB, Park JH, Ihm CG, et al. Acquired perforating dermatosis in patients with chronic renal failure and diabetes mellitus. J Korean Med Sci. 2004;19:283-288.
- Morgan MB, Truitt CA, Taira J, et al. Fibrone
Acquired perforating dermatosis (APD) is an uncommon skin eruption of unclear etiology that most often is associated with diabetes mellitus or chronic renal insufficiency. There are rare reports of APD in association with liver disease or thyroid disease. We report a case of APD in a patient with both primary biliary cirrhosis and Hashimoto thyroiditis in the absence of diabetes mellitus and chronic renal insufficiency. The patient had a partial response to narrowband UVB phototherapy.
Case Report
A 47-year-old woman with a history of primary biliary cirrhosis and rheumatoid arthritis presented with a skin eruption of 4 years' duration. The patient stated that her skin felt pruritic overall, but the lesions had a painful quality. She could not identify any exacerbating or remitting factors. Her medications included prednisone 5 mg daily for rheumatoid arthritis and occasional propoxyphene for pain and zolpidem tartrate for insomnia. She had no personal or family history of diabetes mellitus, renal insufficiency, or similar skin disorders. On physical examination, the patient demonstrated mild scleral icterus. Her skin had a diffuse eruption of erythematous hyperkeratotic papules over the trunk and extremities. Several of these papules appeared excoriated and others appeared to have a central hyperkeratotic crust and hyperpigmented scarring (Figure 1).
Laboratory studies disclosed the following values: alanine aminotransferase, 122 U/L (reference range, 5–50 U/L); aspartate aminotransferase, 95 U/L (reference range, 15–50 U/L); alkaline phosphatase, 603 U/L (reference range, 35–110 U/L); total bilirubin, 6.4 mg/dL (reference range, 0.2–1.5 mg/dL); serum creatinine, 0.6 mg/dL (reference range, 0.7–1.2 mg/dL); and hemoglobin A1c, 4.2% (reference range, 4.4%–5.9%). The patient had a positive antinuclear antibody titer of 1:80 (reference range, <1:40) in a homogenous staining pattern. Her viral hepatitis infection serologies and antismooth muscle antibody titers were all negative. Additionally, her antimitochondrial antibody titers were positive, 1:160 (reference range, <1:20); thyrotropin levels were increased, 10.3 mIU/L (reference range, 0.3–4.7 mIU/L); and thyroid peroxidase antibodies were elevated, 14.8 IU/mL (reference range, <2.0 IU/mL).
Results of a liver biopsy demonstrated biliary injury and loss, with bridging fibrosis, consistent with stage III primary biliary cirrhosis. Results of a skin punch biopsy were remarkable for hyperkeratosis, epidermal acanthosis, and a channel filled with neutrophils and both eosinophilic and basophilic staining debris traversing the epidermis (Figure 2). A chronic infiltrate of lymphocytes, histiocytes, and neutrophils was present at the base of the transepidermal channel. Results of a Masson trichrome stain did not demonstrate substantial amounts of collagen; results of an acid orcein stain showed some elastin fibers at the base of the transepidermal channel (Figures 3 and 4). This combination of clinical and histopathologic findings was consistent with acquired perforating dermatosis (APD).
In addition to starting thyroid hormone replacement therapy for Hashimoto thyroiditis, the patient began narrowband UVB treatments 3 times weekly for her skin condition. After several months of thyroid hormone replacement therapy and 60 narrowband UVB treatments that led to normalization of her thyrotropin levels, the patient noted no new lesions, though the resolution of her old lesions was not substantial.
Comment
APD, often thought to be synonymous with acquired reactive perforating collagenosis, is a skin condition that is usually associated with pruritus and characterized by umbilicated papules and nodules with a central adherent plug. These nodules are manifestations of transepidermal elimination of ill-defined material containing cellular debris, elastin, and collagen. The nosology of perforating dermatoses has been complicated by considerable overlap among the different entities. It generally is accepted that APD is differentiated from other primary perforating dermatoses by the presence of an underlying systemic disease.In contradistinction to the primary perforating disorders Kyrle disease, reactive perforating collagenosis, elastosis perforans serpiginosa, and perforating folliculitis, APD characteristically is associated with diabetes mellitus, chronic renal insufficiency, or both, and does not display a familial inheritance pattern.1 Up to 11% (8/72) of patients who received hemodialysis have been reported to have APD.2 There also have been case reports of APD in association with atopic dermatitis,3 scabies infestation,4,5 herpes zoster,6-8 human immunodeficiency virus,9 pulmonary fibrosis,10 thyroid disease,11 and liver disease.12-17
In contrast to associations between APD and diabetes mellitus or renal disease, associations between APD and liver disease are reported less frequently. Kahana et al12 reported 2 cases of perforating folliculitis associated with primary sclerosing cholangitis. Salomon et al13 reported a case of a 46-year-old man with alcoholic liver disease who subsequently developed a perforating dermatosis. Lee et al14 reported a case of a 69-year-old man with hepatitis B and hepatocellular carcinoma who developed APD. Tang et al15 reported a case of a 33-year-old man with diabetes mellitus and hepatitis B who developed APD. Faver et al11 reported a case of a 71-year-old man with “liver dysfunction” and nephropathy and a case of a 54-year-old woman with diabetes mellitus and “chronic active hepatitis,” both with APD. Skiba et al16 reported a case of a 33-year-old woman with diabetes mellitus and sclerosing cholangitis who also developed APD. Fujimoto et al17 reported 2 cases of APD with liver disease—one patient was a 50-year-old man with unspecified hepatitis, and the other patient was a 75-year-old man with diabetes mellitus and a hepatoma.
Reports of associations between APD and thyroid disease are even more infrequent than reports of APD and liver disease. Faver et al11 reported 3 cases of APD associated with hypothyroidism; 2 of these patients had concomitant diabetes mellitus. Although reports of associations between APD and thyroid disease are rare, it is unclear if this is because of a true rarity of coincidence or because the thyroid status of these patients typically is not checked or reported.
The pathogenesis of APD is unknown. The prominent association of APD with the symptom of pruritus has led many authors to speculate on a connection between scratching, trauma, and APD.3,18 Some studies have demonstrated increased expression of the 67-kD elastin receptor in lesions of perforating dermatoses; however, this expression is not uniformly elevated and the significance of this expression is not known.17 Other studies have found elevated levels of the extracellular matrix protein fibronectin in lesions of APD, but similar to the elastin receptor findings, the significance of this observation is unknown.19,20
Histopathologically, lesions of APD are characterized by acanthosis and focal vacuolar alteration in the basal epidermis, with an associated underlying mixed infiltrate of lymphocytes, macrophages, neutrophils, and occasional mast cells. A transepidermal canal can be identified that often contains parakeratotic keratin, degenerated inflammatory cells, elastin, and collagen. The elastin and collagen in these lesions appear normal ultrastructurally, and results of direct immunofluorescence studies are negative.21,22 In one study of APD associated with diabetes mellitus and renal insufficiency, needlelike crystals with some degree of calcification were identified. They were postulated to be uric acid or calcium hydroxyapatite crystals.23
Treatment of APD has proven to be challenging. Some clinicians report improvement of APD with topical retinoids19,24,25; topical, intralesional, or systemic corticosteroids26; oral doxycycline27; oral thalidomide9; oral allopurinol28; psoralen plus UVA phototherapy29; and broadband UVB phototherapy.11,30 Reports of narrowband UVB phototherapy in the treatment of APD appear promising.31,32 Ohe et al33 reported a case series of 5 patients with APD; all patients responded to narrowband UVB phototherapy.
Acquired perforating dermatosis (APD) is an uncommon skin eruption of unclear etiology that most often is associated with diabetes mellitus or chronic renal insufficiency. There are rare reports of APD in association with liver disease or thyroid disease. We report a case of APD in a patient with both primary biliary cirrhosis and Hashimoto thyroiditis in the absence of diabetes mellitus and chronic renal insufficiency. The patient had a partial response to narrowband UVB phototherapy.
Case Report
A 47-year-old woman with a history of primary biliary cirrhosis and rheumatoid arthritis presented with a skin eruption of 4 years' duration. The patient stated that her skin felt pruritic overall, but the lesions had a painful quality. She could not identify any exacerbating or remitting factors. Her medications included prednisone 5 mg daily for rheumatoid arthritis and occasional propoxyphene for pain and zolpidem tartrate for insomnia. She had no personal or family history of diabetes mellitus, renal insufficiency, or similar skin disorders. On physical examination, the patient demonstrated mild scleral icterus. Her skin had a diffuse eruption of erythematous hyperkeratotic papules over the trunk and extremities. Several of these papules appeared excoriated and others appeared to have a central hyperkeratotic crust and hyperpigmented scarring (Figure 1).
Laboratory studies disclosed the following values: alanine aminotransferase, 122 U/L (reference range, 5–50 U/L); aspartate aminotransferase, 95 U/L (reference range, 15–50 U/L); alkaline phosphatase, 603 U/L (reference range, 35–110 U/L); total bilirubin, 6.4 mg/dL (reference range, 0.2–1.5 mg/dL); serum creatinine, 0.6 mg/dL (reference range, 0.7–1.2 mg/dL); and hemoglobin A1c, 4.2% (reference range, 4.4%–5.9%). The patient had a positive antinuclear antibody titer of 1:80 (reference range, <1:40) in a homogenous staining pattern. Her viral hepatitis infection serologies and antismooth muscle antibody titers were all negative. Additionally, her antimitochondrial antibody titers were positive, 1:160 (reference range, <1:20); thyrotropin levels were increased, 10.3 mIU/L (reference range, 0.3–4.7 mIU/L); and thyroid peroxidase antibodies were elevated, 14.8 IU/mL (reference range, <2.0 IU/mL).
Results of a liver biopsy demonstrated biliary injury and loss, with bridging fibrosis, consistent with stage III primary biliary cirrhosis. Results of a skin punch biopsy were remarkable for hyperkeratosis, epidermal acanthosis, and a channel filled with neutrophils and both eosinophilic and basophilic staining debris traversing the epidermis (Figure 2). A chronic infiltrate of lymphocytes, histiocytes, and neutrophils was present at the base of the transepidermal channel. Results of a Masson trichrome stain did not demonstrate substantial amounts of collagen; results of an acid orcein stain showed some elastin fibers at the base of the transepidermal channel (Figures 3 and 4). This combination of clinical and histopathologic findings was consistent with acquired perforating dermatosis (APD).
In addition to starting thyroid hormone replacement therapy for Hashimoto thyroiditis, the patient began narrowband UVB treatments 3 times weekly for her skin condition. After several months of thyroid hormone replacement therapy and 60 narrowband UVB treatments that led to normalization of her thyrotropin levels, the patient noted no new lesions, though the resolution of her old lesions was not substantial.
Comment
APD, often thought to be synonymous with acquired reactive perforating collagenosis, is a skin condition that is usually associated with pruritus and characterized by umbilicated papules and nodules with a central adherent plug. These nodules are manifestations of transepidermal elimination of ill-defined material containing cellular debris, elastin, and collagen. The nosology of perforating dermatoses has been complicated by considerable overlap among the different entities. It generally is accepted that APD is differentiated from other primary perforating dermatoses by the presence of an underlying systemic disease.In contradistinction to the primary perforating disorders Kyrle disease, reactive perforating collagenosis, elastosis perforans serpiginosa, and perforating folliculitis, APD characteristically is associated with diabetes mellitus, chronic renal insufficiency, or both, and does not display a familial inheritance pattern.1 Up to 11% (8/72) of patients who received hemodialysis have been reported to have APD.2 There also have been case reports of APD in association with atopic dermatitis,3 scabies infestation,4,5 herpes zoster,6-8 human immunodeficiency virus,9 pulmonary fibrosis,10 thyroid disease,11 and liver disease.12-17
In contrast to associations between APD and diabetes mellitus or renal disease, associations between APD and liver disease are reported less frequently. Kahana et al12 reported 2 cases of perforating folliculitis associated with primary sclerosing cholangitis. Salomon et al13 reported a case of a 46-year-old man with alcoholic liver disease who subsequently developed a perforating dermatosis. Lee et al14 reported a case of a 69-year-old man with hepatitis B and hepatocellular carcinoma who developed APD. Tang et al15 reported a case of a 33-year-old man with diabetes mellitus and hepatitis B who developed APD. Faver et al11 reported a case of a 71-year-old man with “liver dysfunction” and nephropathy and a case of a 54-year-old woman with diabetes mellitus and “chronic active hepatitis,” both with APD. Skiba et al16 reported a case of a 33-year-old woman with diabetes mellitus and sclerosing cholangitis who also developed APD. Fujimoto et al17 reported 2 cases of APD with liver disease—one patient was a 50-year-old man with unspecified hepatitis, and the other patient was a 75-year-old man with diabetes mellitus and a hepatoma.
Reports of associations between APD and thyroid disease are even more infrequent than reports of APD and liver disease. Faver et al11 reported 3 cases of APD associated with hypothyroidism; 2 of these patients had concomitant diabetes mellitus. Although reports of associations between APD and thyroid disease are rare, it is unclear if this is because of a true rarity of coincidence or because the thyroid status of these patients typically is not checked or reported.
The pathogenesis of APD is unknown. The prominent association of APD with the symptom of pruritus has led many authors to speculate on a connection between scratching, trauma, and APD.3,18 Some studies have demonstrated increased expression of the 67-kD elastin receptor in lesions of perforating dermatoses; however, this expression is not uniformly elevated and the significance of this expression is not known.17 Other studies have found elevated levels of the extracellular matrix protein fibronectin in lesions of APD, but similar to the elastin receptor findings, the significance of this observation is unknown.19,20
Histopathologically, lesions of APD are characterized by acanthosis and focal vacuolar alteration in the basal epidermis, with an associated underlying mixed infiltrate of lymphocytes, macrophages, neutrophils, and occasional mast cells. A transepidermal canal can be identified that often contains parakeratotic keratin, degenerated inflammatory cells, elastin, and collagen. The elastin and collagen in these lesions appear normal ultrastructurally, and results of direct immunofluorescence studies are negative.21,22 In one study of APD associated with diabetes mellitus and renal insufficiency, needlelike crystals with some degree of calcification were identified. They were postulated to be uric acid or calcium hydroxyapatite crystals.23
Treatment of APD has proven to be challenging. Some clinicians report improvement of APD with topical retinoids19,24,25; topical, intralesional, or systemic corticosteroids26; oral doxycycline27; oral thalidomide9; oral allopurinol28; psoralen plus UVA phototherapy29; and broadband UVB phototherapy.11,30 Reports of narrowband UVB phototherapy in the treatment of APD appear promising.31,32 Ohe et al33 reported a case series of 5 patients with APD; all patients responded to narrowband UVB phototherapy.
- Rapini RP, Hebert AA, Drucker CR. Acquired perforating dermatosis: evidence for combined transepidermal elimination of both collagen and elastic fibers. Arch Dermatol. 1989;125:1074-1078.
- Morton CA, Henderson IS, Jones MC, et al. Acquired perforating dermatosis in a British dialysis population. Br J Dermatol. 1996;135:671-677.
- Thiele-Ochel S, Schneider LA, Reinhold K, et al. Acquired perforating dermatosis: is it due to damage by scratching? Br J Dermatol. 2001;145:173-174.
- Hinrichs W, Breuckmann F, Altmeyer P, et al. Acquired perforating dermatosis: a report on 4 cases associated with scabies infection. J Am Acad Dermatol. 2004;51:665-667.
- Kurschat P, Kroger A, Scharffetter-Kochanek K, et al. Acquired reactive perforating collagenosis triggered by scabies infection. Acta Derm Venereol. 2000;80:384-385.
- Bang SW, Kim YK, Whang KU. Acquired reactive perforating collagenosis: unilateral umbilicated papules along the lesions of herpes zoster. J Am Acad Dermatol. 1997;36:778-779.
- Lee HN, Lee DW, Lee JY, et al. Two cases of reactive perforating collagenosis arising at the site of healed herpes zoster. Int J Dermatol. 2001;40:191-192.
- Zanardo L, Stolz W, Landthaler M, et al. Reactive perforating collagenosis after disseminated zoster. Dermatology. 2001;203:273-275.
- Rubio FA, Herranz P, Robayna G, et al. Perforating folliculitis: report of a case in an HIV-infected man. J Am Acad Dermatol. 1999;40:300-302.
- Tsuboi H, Mukuno A, Sato N, et al. Acquired reactive perforating collagenosis in a patient with lung fibrosis. J Dermatol. 2004;31:916-919.
- Faver IR, Daoud MS, Su WP. Acquired reactive perforating collagenosis. report of six cases and review of the literature. J Am Acad Dermatol. 1994;30:575-580.
- Kahana M, Schewach-Millet M, Trau H, et al. Perforating folliculitis in association with primary sclerosing cholangitis. Am J Dermatopathol. 1985;7:271-276.
- Salomon RJ, Baden TJ, Gammon WR. Kyrle's disease and hepatic insufficiency. Arch Dermatol. 1986;122:18-19.
- Lee YS, Vijayasingam S, Tan YO, et al. Acquired perforating dermatosis associated with recurrent hepatocellular carcinoma. Int J Dermatol. 1996;35:743-745.
- Tang WY, Chong LY, Lam SY, et al. Acquired reactive perforating collagenosis in two Chinese patients. Int J Dermatol. 1995;34:196-198.
- Skiba G, Milkiewicz P, Mutimer D, et al. Successful treatment of acquired perforating dermatosis with rifampicin in an Asian patient with sclerosing cholangitis. Liver. 1999;19:160-163.
- Fujimoto N, Akagi A, Tajima S, et al. Expression of the 67-kDa elastin receptor in perforating skin disorders. Br J Dermatol. 2002;146:74-79.
- Hong SB, Park JH, Ihm CG, et al. Acquired perforating dermatosis in patients with chronic renal failure and diabetes mellitus. J Korean Med Sci. 2004;19:283-288.
- Morgan MB, Truitt CA, Taira J, et al. Fibrone
- Rapini RP, Hebert AA, Drucker CR. Acquired perforating dermatosis: evidence for combined transepidermal elimination of both collagen and elastic fibers. Arch Dermatol. 1989;125:1074-1078.
- Morton CA, Henderson IS, Jones MC, et al. Acquired perforating dermatosis in a British dialysis population. Br J Dermatol. 1996;135:671-677.
- Thiele-Ochel S, Schneider LA, Reinhold K, et al. Acquired perforating dermatosis: is it due to damage by scratching? Br J Dermatol. 2001;145:173-174.
- Hinrichs W, Breuckmann F, Altmeyer P, et al. Acquired perforating dermatosis: a report on 4 cases associated with scabies infection. J Am Acad Dermatol. 2004;51:665-667.
- Kurschat P, Kroger A, Scharffetter-Kochanek K, et al. Acquired reactive perforating collagenosis triggered by scabies infection. Acta Derm Venereol. 2000;80:384-385.
- Bang SW, Kim YK, Whang KU. Acquired reactive perforating collagenosis: unilateral umbilicated papules along the lesions of herpes zoster. J Am Acad Dermatol. 1997;36:778-779.
- Lee HN, Lee DW, Lee JY, et al. Two cases of reactive perforating collagenosis arising at the site of healed herpes zoster. Int J Dermatol. 2001;40:191-192.
- Zanardo L, Stolz W, Landthaler M, et al. Reactive perforating collagenosis after disseminated zoster. Dermatology. 2001;203:273-275.
- Rubio FA, Herranz P, Robayna G, et al. Perforating folliculitis: report of a case in an HIV-infected man. J Am Acad Dermatol. 1999;40:300-302.
- Tsuboi H, Mukuno A, Sato N, et al. Acquired reactive perforating collagenosis in a patient with lung fibrosis. J Dermatol. 2004;31:916-919.
- Faver IR, Daoud MS, Su WP. Acquired reactive perforating collagenosis. report of six cases and review of the literature. J Am Acad Dermatol. 1994;30:575-580.
- Kahana M, Schewach-Millet M, Trau H, et al. Perforating folliculitis in association with primary sclerosing cholangitis. Am J Dermatopathol. 1985;7:271-276.
- Salomon RJ, Baden TJ, Gammon WR. Kyrle's disease and hepatic insufficiency. Arch Dermatol. 1986;122:18-19.
- Lee YS, Vijayasingam S, Tan YO, et al. Acquired perforating dermatosis associated with recurrent hepatocellular carcinoma. Int J Dermatol. 1996;35:743-745.
- Tang WY, Chong LY, Lam SY, et al. Acquired reactive perforating collagenosis in two Chinese patients. Int J Dermatol. 1995;34:196-198.
- Skiba G, Milkiewicz P, Mutimer D, et al. Successful treatment of acquired perforating dermatosis with rifampicin in an Asian patient with sclerosing cholangitis. Liver. 1999;19:160-163.
- Fujimoto N, Akagi A, Tajima S, et al. Expression of the 67-kDa elastin receptor in perforating skin disorders. Br J Dermatol. 2002;146:74-79.
- Hong SB, Park JH, Ihm CG, et al. Acquired perforating dermatosis in patients with chronic renal failure and diabetes mellitus. J Korean Med Sci. 2004;19:283-288.
- Morgan MB, Truitt CA, Taira J, et al. Fibrone
Syringomatous Carcinoma in a Young Patient Treated With Mohs Micrographic Surgery
Syringomatous carcinoma (SC), considered by some to be a variant of microcystic adnexal carcinoma (MAC),1 is a rare malignant neoplasm of sweat gland origin. SC encompasses a range of neoplasms with different degrees of differentiation, and its nomenclature has varied over the years. SC also has been referred to as syringoid eccrine carcinoma,2 basal cell tumor with eccrine differentiation,3 malignant syringoma,4 and sclerosing sweat duct carcinoma.5 Its diagnosis has been a dilemma in a number of reported cases, probably due to the combination of its rarity and thus limited clinical and histopathologic information, microscopic similarities to other benign and malignant neoplasms, and characteristic histologic features that may only be apparent in surgical excisions containing deeper tissue. We report a case of SC that masqueraded as an epidermoid cyst in an unusually young patient.
Case Report
A 23-year-old Asian man, who was otherwise healthy, presented with an asymptomatic slowly enlarging nodule of one year's duration on the right medial eyebrow. Prior treatment with intralesional steroid injections resulted in minimal improvement. The patient had no personal or family history of skin cancers. Physical examination results demonstrated a well-demarcated, mobile, nontender subcutaneous nodule measuring 7 mm in diameter. The clinical presentation favored a diagnosis of an epidermal inclusion cyst, and the patient underwent surgical excision of the lesion. Results of the histopathologic examination revealed a neoplasm in the dermis consisting of bands and nests of pale staining basaloid cells extending between the collagen fibers (Figure 1). There were focal areas of ductal differentiation, scattered individual necrotic cells, moderate dermal fibrosis, and chronic inflammation with numerous eo-sinophils. Moderate nuclear atypia also was present (Figure 2). Perineural involvement was not seen. Results of immunohistochemical analysis revealed positive staining for high—and low—molecular-weight cytokeratins, as well as carcinoembryonic antigen (CEA)(Figure 3). There was scattered positivity with S-100 protein in occasional cells lining lumina and in dendritic cells (Figure 4). The histopathologic findings supported the diagnosis of SC. Because the neoplasm extended to the surgical margins of the specimen, repeat surgical excision with continuous microscopic control under the Mohs micrographic technique was performed to prevent local recurrence and spare normal tissue. At the 18-month follow-up visit, no local recurrence was seen.
Comment SC is a rare, malignant sweat gland neoplasm that usually occurs in the fourth and fifth decades of life.4-8 SC typically presents as a slow-growing, solitary, painless nodule or indurated plaque on the head or neck region.6-8 It has been frequently found on the upper and lower lips; however, it also has been reported to occur on the finger and breast.9,10 Predisposing factors for the development of SC are unclear11 but may include previous radiation to the face and history of receiving an organ transplant with immunosuppressive drug therapy.12-17 Histopathologically, SC is characterized by asymmetric and deep dermal invasion of tumor cells, perineural involvement, ductal formation, keratin-filled cysts, multiple nests of basaloid or squamous cells, and desmoplasia of the surrounding dermal stroma (Table 1).5,6 Some authors consider SC to be closely related to MAC but generally describe SC as more basaloid with larger tubules and a more sclerotic stroma than MAC.18-26 If histologic examination of SC is limited to the superficial dermis, SC demonstrates similarities to other neoplasms, including syringomas, trichoadenomas, trichoepitheliomas, basal cell carcinomas, or squamous cell carcinomas. In the reported cases in which SC was initially misdiagnosed as another benign or malignant neoplasm, many misdiagnoses were due to either a benign clinical appearance of the lesion or biopsy specimens that were too superficial to contain the deeper characteristic histologic features of SC.8,9,11,27-30
Immunohistochemical studies can facilitate the diagnosis of SC and differentiate it from other neoplasms. SC stains positively for CEA, S-100 protein, epithelial membrane antigen, cyto-keratin, and gross cystic disease fluid protein 15,31 all of which aid in the confirmation of a sweat gland neoplasm (Table 2).8,32,33,39 Positivity for CEA in the ductal lining cells and the luminal contents of tumor ducts confirms sweat gland differentiation.25,33,34 This ductal immunoreactivity to CEA appears to be one of the most reliable findings to differentiate SC and MAC from other adnexal tumors, especially desmoplastic trichoepithelioma, which may be one of the more challenging histo-pathologic differential diagnoses.35 In addition, epithelial membrane antigen positivity can be found in the areas showing glandular features.35 This can assist in distinguishing SC from a desmoplastic trichoepithelioma or sclerosing type basal cell carcinoma, both of which demonstrate negativity to epithelial membrane antigen.35 S-100 protein positivity in dendritic cells, as well as in some cords and ducts in SC, further verifies dendritic differentiation toward sweat gland structures and is useful as an adjunct in the confirmation of glandular differentiation.25,33,34,36
Without proper and timely diagnosis and management, SC can cause severe patient morbidity. Although SC rarely metastasizes and can have an indolent course, it can be locally de-structive and lead to potentially disfiguring outcomes.5-7 SC can invade deeply and infiltrate into the dermis, subcutaneous fat tissue, muscle, perichondrium, periosteum, and galea.8 Goto et al9 reported a case of an SC that was initially misdiagnosed as a basal cell carcinoma of the left middle finger. The deeper, characteristic features of SC were not recognized until after the affected finger required amputation due to erosion of the bone. Hoppenreijs et al11 described an aggressive case of an SC arising at a site of previously irradiated squamous cell carcinoma of the lower eyelid. Extensive involvement of the SC in the orbit led to the recommendation of an orbital exenter-ation; however, it was not performed because of the poor clinical condition of the patient. Treatments for SC have included wide local excision and Mohs micrographic surgery (MMS). SC treatment with wide local excision often resulted in incomplete excision of the neoplasm despite having taken an adequate margin around the clinically assessable tumor.5 Cases of SC treated with wide local excision had a recurrence rate of 47%.5 The positive surgical margins following wide local excision may be due to the deep infiltration of SC, which frequently exceeds the clinically predicted size of the tumor.5 Due to the close relationship of MAC and SC, we feel that MMS treatment of SC will reduce recurrences as it has for MAC. Currently, there is strong support for the treatment of MAC with MMS as a gold standard to ensure complete clearance of the neoplasm and to reduce the local recurrence rate.12,13,17,21,22,37,38 In a study of MAC by Chiller et al,37 the authors demonstrated a median 4-fold increase in defect size when they compared the clinically estimated pretreatment size of the lesion with the MMS-determined posttreatment size of the lesion. The authors therefore suggest that, similar to the MMS-treated lesions, the lesions completely treated with wide local excision also would produce a defect size that is at least 4 times greater than the predicted pretreatment size of the lesion. Because wide local excision relies on predicted margins of the lesion, which the authors have shown can be greatly underestimated, Chiller et al37 argue that the use of MMS, which does not rely on predicted margins, is a reasonable first-line therapeutic modality for effectively treating patients with MAC. Furthermore, MMS allows for the examination of the entire peripheral and deep margins of the lesion, which is critical when considering the deep infiltrative nature of MAC. The reported local recurrence rate of MAC treated with MMS is 0% to 5%,12,13,21,26,38 which is much lower than the reported local recurrence rate following treatment with wide local excision. This reduced recurrence rate found in MAC cases treated with MMS is probably due to the ability to confirm complete removal of the neoplasm with MMS.
Conclusion To our knowledge, this case report describes the occurrence of SC, a rare sweat gland neoplasm, in the youngest reported patient and is only the second reported case of SC treated with MMS. Adequate sampling of tissue with an excisional biopsy allowed for appropriate evaluation with histologic and immunohistochemical studies to arrive at the diagnosis that could easily have been missed with a superficial biopsy. In our patient, histopathologic evaluation showed typical nests of basaloid cells, ductal differentiation, and ductal fibrosis seen in SC. However, perineural involvement that is particularly characteristic of SC was not present. This may portend a better prognosis for our patient whose tumor was completely excised after one stage of MMS and has not shown evidence of recurrence at the 18-month follow-up visit. MMS allowed for evaluation of the entire surgical margin and decreased risk of local recurrence resulting from an incomplete excision. In addition, it also allowed for sparing of normal tissue in a cosmetically sensitive area where SC commonly occurs. In summary, this case highlights the importance of including SC in the differential diagnosis of an enlarging cystic lesion in a younger patient and its successful treatment with MMS.
- Weedon D. Tumors of cutaneous appendages. In: Weedon D, ed. Skin Pathology. 2nd ed. London, England: Churchill Livingstone; 2002:897.
- Sanchez Yus E, Requena Caballero L, Garcia Salazar I, et al. Clear cell syringoid eccrine carcinoma. Am J Dermatopathol. 1987;9:225-231.
- Freeman RG, Winkelmann RK. Basal cell tumor with eccrine differentiation (eccrine epithelioma). Arch Dermatol. 1969;100:234-242.
- Glatt HJ, Proia AD, Tsoy EA, et al. Malignant syringoma of the eyelid. Ophthalmology. 1984;91:987-990.
- Cooper PH, Mills SE, Leonard DD, et al. Sclerosing sweat duct (syringomatous) carcinoma. Am J Surg Pathol. 1985;9:422-433.
- Mehregan AH, Hashimoto K, Rahbari H. Eccrine adenocarcinoma: a clinicopathologic study of 35 cases. Arch Dermatol. 1983;119:104-114.
- Wick MR, Goellner JR, Wolfe JT III, et al. Adnexal carcinomas of the skin, I: eccrine carcinomas. Cancer. 1985;56:1147-1162.
- Abenoza P, Ackerman AB. Syringomatous carcinomas. In: Abenoza P, Ackerman AB, eds. Neoplasms with Eccrine Differentiation. Philadelphia, Pa: Lea & Febiger; 1990:371-412.
- Goto M, Sonoda T, Shibuya H, et al. Digital syringomatous carcinoma mimicking basal cell carcinoma. Br J Dermatol. 2001;144:438-439.
- Urso C. Syringomatous breast carcinoma and correlated lesions. Pathologica. 1996;88:196-199.
- Hoppenreijs VP, Reuser TT, Mooy CM, et al. Syringomatous carcinoma of the eyelid and orbit: a clinical and histopathological challenge. Br J Ophthalmol. 1997;81:668-672.
- Snow S, Madjar DD, Hardy S, et al. Microcystic adnexal carcinoma: report of 13 cases and review of the literature. Dermatol Surg. 2001;27:401-408.
- Friedman PM, Friedman RH, Jiang SB, et al. Microcystic adnexal carcinoma: collaborative series review and update. J Am Acad Dermatol. 1999;41:225-231.
- Antley CA, Carney M, Smoller BR. Microcystic adnexal carcinoma arising in the setting of previous radiation therapy. J Cutan Pathol. 1999;26:48-50.
- Borenstein A, Seidman DS, Trau H, et al. Microcystic adnexal carcinoma following radiotherapy in childhood. Am J Med Sci. 1991;301:259-261.
- Fleischmann HE, Roth RJ, Wood C, et al. Microcystic adnexal carcinoma treated by microscopically controlled excision. J Dermatol Surg Oncol. 1984;10:873-875.
- Schwarze HP, Loche F, Lamant L, et al. Microcystic adnexal carcinoma induced by multiple radiation therapy. Int J Dermatol. 2000;39:369-372.
- Cooper PH, Mills SE. Microcystic adnexal carcinoma. J Am Acad Dermatol. 1984;10:908-914.
- Hamm JC, Argenta LC, Swanson NA. Microcystic adnexal carcinoma: an unpredictable aggressive neoplasm. Ann Plast Surg. 1987;19:173-180.
- Birkby CS, Argenyi ZB, Whitaker DC. Microcystic adnexal carcinoma with mandibular invasion and bone marrow replacement. J Dermatol Surg Oncol. 1989;15:308-312.
- Leibovitch I, Huilgol SC, Selva D, et al. Microcystic adnexal carcinoma: treatment with Mohs micrographic surgery. J Am Acad Dermatol. 2005;52:295-300.
- Gardner ES, Goldb
Syringomatous carcinoma (SC), considered by some to be a variant of microcystic adnexal carcinoma (MAC),1 is a rare malignant neoplasm of sweat gland origin. SC encompasses a range of neoplasms with different degrees of differentiation, and its nomenclature has varied over the years. SC also has been referred to as syringoid eccrine carcinoma,2 basal cell tumor with eccrine differentiation,3 malignant syringoma,4 and sclerosing sweat duct carcinoma.5 Its diagnosis has been a dilemma in a number of reported cases, probably due to the combination of its rarity and thus limited clinical and histopathologic information, microscopic similarities to other benign and malignant neoplasms, and characteristic histologic features that may only be apparent in surgical excisions containing deeper tissue. We report a case of SC that masqueraded as an epidermoid cyst in an unusually young patient.
Case Report
A 23-year-old Asian man, who was otherwise healthy, presented with an asymptomatic slowly enlarging nodule of one year's duration on the right medial eyebrow. Prior treatment with intralesional steroid injections resulted in minimal improvement. The patient had no personal or family history of skin cancers. Physical examination results demonstrated a well-demarcated, mobile, nontender subcutaneous nodule measuring 7 mm in diameter. The clinical presentation favored a diagnosis of an epidermal inclusion cyst, and the patient underwent surgical excision of the lesion. Results of the histopathologic examination revealed a neoplasm in the dermis consisting of bands and nests of pale staining basaloid cells extending between the collagen fibers (Figure 1). There were focal areas of ductal differentiation, scattered individual necrotic cells, moderate dermal fibrosis, and chronic inflammation with numerous eo-sinophils. Moderate nuclear atypia also was present (Figure 2). Perineural involvement was not seen. Results of immunohistochemical analysis revealed positive staining for high—and low—molecular-weight cytokeratins, as well as carcinoembryonic antigen (CEA)(Figure 3). There was scattered positivity with S-100 protein in occasional cells lining lumina and in dendritic cells (Figure 4). The histopathologic findings supported the diagnosis of SC. Because the neoplasm extended to the surgical margins of the specimen, repeat surgical excision with continuous microscopic control under the Mohs micrographic technique was performed to prevent local recurrence and spare normal tissue. At the 18-month follow-up visit, no local recurrence was seen.
Comment SC is a rare, malignant sweat gland neoplasm that usually occurs in the fourth and fifth decades of life.4-8 SC typically presents as a slow-growing, solitary, painless nodule or indurated plaque on the head or neck region.6-8 It has been frequently found on the upper and lower lips; however, it also has been reported to occur on the finger and breast.9,10 Predisposing factors for the development of SC are unclear11 but may include previous radiation to the face and history of receiving an organ transplant with immunosuppressive drug therapy.12-17 Histopathologically, SC is characterized by asymmetric and deep dermal invasion of tumor cells, perineural involvement, ductal formation, keratin-filled cysts, multiple nests of basaloid or squamous cells, and desmoplasia of the surrounding dermal stroma (Table 1).5,6 Some authors consider SC to be closely related to MAC but generally describe SC as more basaloid with larger tubules and a more sclerotic stroma than MAC.18-26 If histologic examination of SC is limited to the superficial dermis, SC demonstrates similarities to other neoplasms, including syringomas, trichoadenomas, trichoepitheliomas, basal cell carcinomas, or squamous cell carcinomas. In the reported cases in which SC was initially misdiagnosed as another benign or malignant neoplasm, many misdiagnoses were due to either a benign clinical appearance of the lesion or biopsy specimens that were too superficial to contain the deeper characteristic histologic features of SC.8,9,11,27-30
Immunohistochemical studies can facilitate the diagnosis of SC and differentiate it from other neoplasms. SC stains positively for CEA, S-100 protein, epithelial membrane antigen, cyto-keratin, and gross cystic disease fluid protein 15,31 all of which aid in the confirmation of a sweat gland neoplasm (Table 2).8,32,33,39 Positivity for CEA in the ductal lining cells and the luminal contents of tumor ducts confirms sweat gland differentiation.25,33,34 This ductal immunoreactivity to CEA appears to be one of the most reliable findings to differentiate SC and MAC from other adnexal tumors, especially desmoplastic trichoepithelioma, which may be one of the more challenging histo-pathologic differential diagnoses.35 In addition, epithelial membrane antigen positivity can be found in the areas showing glandular features.35 This can assist in distinguishing SC from a desmoplastic trichoepithelioma or sclerosing type basal cell carcinoma, both of which demonstrate negativity to epithelial membrane antigen.35 S-100 protein positivity in dendritic cells, as well as in some cords and ducts in SC, further verifies dendritic differentiation toward sweat gland structures and is useful as an adjunct in the confirmation of glandular differentiation.25,33,34,36
Without proper and timely diagnosis and management, SC can cause severe patient morbidity. Although SC rarely metastasizes and can have an indolent course, it can be locally de-structive and lead to potentially disfiguring outcomes.5-7 SC can invade deeply and infiltrate into the dermis, subcutaneous fat tissue, muscle, perichondrium, periosteum, and galea.8 Goto et al9 reported a case of an SC that was initially misdiagnosed as a basal cell carcinoma of the left middle finger. The deeper, characteristic features of SC were not recognized until after the affected finger required amputation due to erosion of the bone. Hoppenreijs et al11 described an aggressive case of an SC arising at a site of previously irradiated squamous cell carcinoma of the lower eyelid. Extensive involvement of the SC in the orbit led to the recommendation of an orbital exenter-ation; however, it was not performed because of the poor clinical condition of the patient. Treatments for SC have included wide local excision and Mohs micrographic surgery (MMS). SC treatment with wide local excision often resulted in incomplete excision of the neoplasm despite having taken an adequate margin around the clinically assessable tumor.5 Cases of SC treated with wide local excision had a recurrence rate of 47%.5 The positive surgical margins following wide local excision may be due to the deep infiltration of SC, which frequently exceeds the clinically predicted size of the tumor.5 Due to the close relationship of MAC and SC, we feel that MMS treatment of SC will reduce recurrences as it has for MAC. Currently, there is strong support for the treatment of MAC with MMS as a gold standard to ensure complete clearance of the neoplasm and to reduce the local recurrence rate.12,13,17,21,22,37,38 In a study of MAC by Chiller et al,37 the authors demonstrated a median 4-fold increase in defect size when they compared the clinically estimated pretreatment size of the lesion with the MMS-determined posttreatment size of the lesion. The authors therefore suggest that, similar to the MMS-treated lesions, the lesions completely treated with wide local excision also would produce a defect size that is at least 4 times greater than the predicted pretreatment size of the lesion. Because wide local excision relies on predicted margins of the lesion, which the authors have shown can be greatly underestimated, Chiller et al37 argue that the use of MMS, which does not rely on predicted margins, is a reasonable first-line therapeutic modality for effectively treating patients with MAC. Furthermore, MMS allows for the examination of the entire peripheral and deep margins of the lesion, which is critical when considering the deep infiltrative nature of MAC. The reported local recurrence rate of MAC treated with MMS is 0% to 5%,12,13,21,26,38 which is much lower than the reported local recurrence rate following treatment with wide local excision. This reduced recurrence rate found in MAC cases treated with MMS is probably due to the ability to confirm complete removal of the neoplasm with MMS.
Conclusion To our knowledge, this case report describes the occurrence of SC, a rare sweat gland neoplasm, in the youngest reported patient and is only the second reported case of SC treated with MMS. Adequate sampling of tissue with an excisional biopsy allowed for appropriate evaluation with histologic and immunohistochemical studies to arrive at the diagnosis that could easily have been missed with a superficial biopsy. In our patient, histopathologic evaluation showed typical nests of basaloid cells, ductal differentiation, and ductal fibrosis seen in SC. However, perineural involvement that is particularly characteristic of SC was not present. This may portend a better prognosis for our patient whose tumor was completely excised after one stage of MMS and has not shown evidence of recurrence at the 18-month follow-up visit. MMS allowed for evaluation of the entire surgical margin and decreased risk of local recurrence resulting from an incomplete excision. In addition, it also allowed for sparing of normal tissue in a cosmetically sensitive area where SC commonly occurs. In summary, this case highlights the importance of including SC in the differential diagnosis of an enlarging cystic lesion in a younger patient and its successful treatment with MMS.
Syringomatous carcinoma (SC), considered by some to be a variant of microcystic adnexal carcinoma (MAC),1 is a rare malignant neoplasm of sweat gland origin. SC encompasses a range of neoplasms with different degrees of differentiation, and its nomenclature has varied over the years. SC also has been referred to as syringoid eccrine carcinoma,2 basal cell tumor with eccrine differentiation,3 malignant syringoma,4 and sclerosing sweat duct carcinoma.5 Its diagnosis has been a dilemma in a number of reported cases, probably due to the combination of its rarity and thus limited clinical and histopathologic information, microscopic similarities to other benign and malignant neoplasms, and characteristic histologic features that may only be apparent in surgical excisions containing deeper tissue. We report a case of SC that masqueraded as an epidermoid cyst in an unusually young patient.
Case Report
A 23-year-old Asian man, who was otherwise healthy, presented with an asymptomatic slowly enlarging nodule of one year's duration on the right medial eyebrow. Prior treatment with intralesional steroid injections resulted in minimal improvement. The patient had no personal or family history of skin cancers. Physical examination results demonstrated a well-demarcated, mobile, nontender subcutaneous nodule measuring 7 mm in diameter. The clinical presentation favored a diagnosis of an epidermal inclusion cyst, and the patient underwent surgical excision of the lesion. Results of the histopathologic examination revealed a neoplasm in the dermis consisting of bands and nests of pale staining basaloid cells extending between the collagen fibers (Figure 1). There were focal areas of ductal differentiation, scattered individual necrotic cells, moderate dermal fibrosis, and chronic inflammation with numerous eo-sinophils. Moderate nuclear atypia also was present (Figure 2). Perineural involvement was not seen. Results of immunohistochemical analysis revealed positive staining for high—and low—molecular-weight cytokeratins, as well as carcinoembryonic antigen (CEA)(Figure 3). There was scattered positivity with S-100 protein in occasional cells lining lumina and in dendritic cells (Figure 4). The histopathologic findings supported the diagnosis of SC. Because the neoplasm extended to the surgical margins of the specimen, repeat surgical excision with continuous microscopic control under the Mohs micrographic technique was performed to prevent local recurrence and spare normal tissue. At the 18-month follow-up visit, no local recurrence was seen.
Comment SC is a rare, malignant sweat gland neoplasm that usually occurs in the fourth and fifth decades of life.4-8 SC typically presents as a slow-growing, solitary, painless nodule or indurated plaque on the head or neck region.6-8 It has been frequently found on the upper and lower lips; however, it also has been reported to occur on the finger and breast.9,10 Predisposing factors for the development of SC are unclear11 but may include previous radiation to the face and history of receiving an organ transplant with immunosuppressive drug therapy.12-17 Histopathologically, SC is characterized by asymmetric and deep dermal invasion of tumor cells, perineural involvement, ductal formation, keratin-filled cysts, multiple nests of basaloid or squamous cells, and desmoplasia of the surrounding dermal stroma (Table 1).5,6 Some authors consider SC to be closely related to MAC but generally describe SC as more basaloid with larger tubules and a more sclerotic stroma than MAC.18-26 If histologic examination of SC is limited to the superficial dermis, SC demonstrates similarities to other neoplasms, including syringomas, trichoadenomas, trichoepitheliomas, basal cell carcinomas, or squamous cell carcinomas. In the reported cases in which SC was initially misdiagnosed as another benign or malignant neoplasm, many misdiagnoses were due to either a benign clinical appearance of the lesion or biopsy specimens that were too superficial to contain the deeper characteristic histologic features of SC.8,9,11,27-30
Immunohistochemical studies can facilitate the diagnosis of SC and differentiate it from other neoplasms. SC stains positively for CEA, S-100 protein, epithelial membrane antigen, cyto-keratin, and gross cystic disease fluid protein 15,31 all of which aid in the confirmation of a sweat gland neoplasm (Table 2).8,32,33,39 Positivity for CEA in the ductal lining cells and the luminal contents of tumor ducts confirms sweat gland differentiation.25,33,34 This ductal immunoreactivity to CEA appears to be one of the most reliable findings to differentiate SC and MAC from other adnexal tumors, especially desmoplastic trichoepithelioma, which may be one of the more challenging histo-pathologic differential diagnoses.35 In addition, epithelial membrane antigen positivity can be found in the areas showing glandular features.35 This can assist in distinguishing SC from a desmoplastic trichoepithelioma or sclerosing type basal cell carcinoma, both of which demonstrate negativity to epithelial membrane antigen.35 S-100 protein positivity in dendritic cells, as well as in some cords and ducts in SC, further verifies dendritic differentiation toward sweat gland structures and is useful as an adjunct in the confirmation of glandular differentiation.25,33,34,36
Without proper and timely diagnosis and management, SC can cause severe patient morbidity. Although SC rarely metastasizes and can have an indolent course, it can be locally de-structive and lead to potentially disfiguring outcomes.5-7 SC can invade deeply and infiltrate into the dermis, subcutaneous fat tissue, muscle, perichondrium, periosteum, and galea.8 Goto et al9 reported a case of an SC that was initially misdiagnosed as a basal cell carcinoma of the left middle finger. The deeper, characteristic features of SC were not recognized until after the affected finger required amputation due to erosion of the bone. Hoppenreijs et al11 described an aggressive case of an SC arising at a site of previously irradiated squamous cell carcinoma of the lower eyelid. Extensive involvement of the SC in the orbit led to the recommendation of an orbital exenter-ation; however, it was not performed because of the poor clinical condition of the patient. Treatments for SC have included wide local excision and Mohs micrographic surgery (MMS). SC treatment with wide local excision often resulted in incomplete excision of the neoplasm despite having taken an adequate margin around the clinically assessable tumor.5 Cases of SC treated with wide local excision had a recurrence rate of 47%.5 The positive surgical margins following wide local excision may be due to the deep infiltration of SC, which frequently exceeds the clinically predicted size of the tumor.5 Due to the close relationship of MAC and SC, we feel that MMS treatment of SC will reduce recurrences as it has for MAC. Currently, there is strong support for the treatment of MAC with MMS as a gold standard to ensure complete clearance of the neoplasm and to reduce the local recurrence rate.12,13,17,21,22,37,38 In a study of MAC by Chiller et al,37 the authors demonstrated a median 4-fold increase in defect size when they compared the clinically estimated pretreatment size of the lesion with the MMS-determined posttreatment size of the lesion. The authors therefore suggest that, similar to the MMS-treated lesions, the lesions completely treated with wide local excision also would produce a defect size that is at least 4 times greater than the predicted pretreatment size of the lesion. Because wide local excision relies on predicted margins of the lesion, which the authors have shown can be greatly underestimated, Chiller et al37 argue that the use of MMS, which does not rely on predicted margins, is a reasonable first-line therapeutic modality for effectively treating patients with MAC. Furthermore, MMS allows for the examination of the entire peripheral and deep margins of the lesion, which is critical when considering the deep infiltrative nature of MAC. The reported local recurrence rate of MAC treated with MMS is 0% to 5%,12,13,21,26,38 which is much lower than the reported local recurrence rate following treatment with wide local excision. This reduced recurrence rate found in MAC cases treated with MMS is probably due to the ability to confirm complete removal of the neoplasm with MMS.
Conclusion To our knowledge, this case report describes the occurrence of SC, a rare sweat gland neoplasm, in the youngest reported patient and is only the second reported case of SC treated with MMS. Adequate sampling of tissue with an excisional biopsy allowed for appropriate evaluation with histologic and immunohistochemical studies to arrive at the diagnosis that could easily have been missed with a superficial biopsy. In our patient, histopathologic evaluation showed typical nests of basaloid cells, ductal differentiation, and ductal fibrosis seen in SC. However, perineural involvement that is particularly characteristic of SC was not present. This may portend a better prognosis for our patient whose tumor was completely excised after one stage of MMS and has not shown evidence of recurrence at the 18-month follow-up visit. MMS allowed for evaluation of the entire surgical margin and decreased risk of local recurrence resulting from an incomplete excision. In addition, it also allowed for sparing of normal tissue in a cosmetically sensitive area where SC commonly occurs. In summary, this case highlights the importance of including SC in the differential diagnosis of an enlarging cystic lesion in a younger patient and its successful treatment with MMS.
- Weedon D. Tumors of cutaneous appendages. In: Weedon D, ed. Skin Pathology. 2nd ed. London, England: Churchill Livingstone; 2002:897.
- Sanchez Yus E, Requena Caballero L, Garcia Salazar I, et al. Clear cell syringoid eccrine carcinoma. Am J Dermatopathol. 1987;9:225-231.
- Freeman RG, Winkelmann RK. Basal cell tumor with eccrine differentiation (eccrine epithelioma). Arch Dermatol. 1969;100:234-242.
- Glatt HJ, Proia AD, Tsoy EA, et al. Malignant syringoma of the eyelid. Ophthalmology. 1984;91:987-990.
- Cooper PH, Mills SE, Leonard DD, et al. Sclerosing sweat duct (syringomatous) carcinoma. Am J Surg Pathol. 1985;9:422-433.
- Mehregan AH, Hashimoto K, Rahbari H. Eccrine adenocarcinoma: a clinicopathologic study of 35 cases. Arch Dermatol. 1983;119:104-114.
- Wick MR, Goellner JR, Wolfe JT III, et al. Adnexal carcinomas of the skin, I: eccrine carcinomas. Cancer. 1985;56:1147-1162.
- Abenoza P, Ackerman AB. Syringomatous carcinomas. In: Abenoza P, Ackerman AB, eds. Neoplasms with Eccrine Differentiation. Philadelphia, Pa: Lea & Febiger; 1990:371-412.
- Goto M, Sonoda T, Shibuya H, et al. Digital syringomatous carcinoma mimicking basal cell carcinoma. Br J Dermatol. 2001;144:438-439.
- Urso C. Syringomatous breast carcinoma and correlated lesions. Pathologica. 1996;88:196-199.
- Hoppenreijs VP, Reuser TT, Mooy CM, et al. Syringomatous carcinoma of the eyelid and orbit: a clinical and histopathological challenge. Br J Ophthalmol. 1997;81:668-672.
- Snow S, Madjar DD, Hardy S, et al. Microcystic adnexal carcinoma: report of 13 cases and review of the literature. Dermatol Surg. 2001;27:401-408.
- Friedman PM, Friedman RH, Jiang SB, et al. Microcystic adnexal carcinoma: collaborative series review and update. J Am Acad Dermatol. 1999;41:225-231.
- Antley CA, Carney M, Smoller BR. Microcystic adnexal carcinoma arising in the setting of previous radiation therapy. J Cutan Pathol. 1999;26:48-50.
- Borenstein A, Seidman DS, Trau H, et al. Microcystic adnexal carcinoma following radiotherapy in childhood. Am J Med Sci. 1991;301:259-261.
- Fleischmann HE, Roth RJ, Wood C, et al. Microcystic adnexal carcinoma treated by microscopically controlled excision. J Dermatol Surg Oncol. 1984;10:873-875.
- Schwarze HP, Loche F, Lamant L, et al. Microcystic adnexal carcinoma induced by multiple radiation therapy. Int J Dermatol. 2000;39:369-372.
- Cooper PH, Mills SE. Microcystic adnexal carcinoma. J Am Acad Dermatol. 1984;10:908-914.
- Hamm JC, Argenta LC, Swanson NA. Microcystic adnexal carcinoma: an unpredictable aggressive neoplasm. Ann Plast Surg. 1987;19:173-180.
- Birkby CS, Argenyi ZB, Whitaker DC. Microcystic adnexal carcinoma with mandibular invasion and bone marrow replacement. J Dermatol Surg Oncol. 1989;15:308-312.
- Leibovitch I, Huilgol SC, Selva D, et al. Microcystic adnexal carcinoma: treatment with Mohs micrographic surgery. J Am Acad Dermatol. 2005;52:295-300.
- Gardner ES, Goldb
- Weedon D. Tumors of cutaneous appendages. In: Weedon D, ed. Skin Pathology. 2nd ed. London, England: Churchill Livingstone; 2002:897.
- Sanchez Yus E, Requena Caballero L, Garcia Salazar I, et al. Clear cell syringoid eccrine carcinoma. Am J Dermatopathol. 1987;9:225-231.
- Freeman RG, Winkelmann RK. Basal cell tumor with eccrine differentiation (eccrine epithelioma). Arch Dermatol. 1969;100:234-242.
- Glatt HJ, Proia AD, Tsoy EA, et al. Malignant syringoma of the eyelid. Ophthalmology. 1984;91:987-990.
- Cooper PH, Mills SE, Leonard DD, et al. Sclerosing sweat duct (syringomatous) carcinoma. Am J Surg Pathol. 1985;9:422-433.
- Mehregan AH, Hashimoto K, Rahbari H. Eccrine adenocarcinoma: a clinicopathologic study of 35 cases. Arch Dermatol. 1983;119:104-114.
- Wick MR, Goellner JR, Wolfe JT III, et al. Adnexal carcinomas of the skin, I: eccrine carcinomas. Cancer. 1985;56:1147-1162.
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