Letters to the Editor
tous plaque measuring 3 cm 9 1.8 cm was observed on the right calf (Fig. 1a). Histopathology showed hyperkeratosis and marked acanthosis with full-thickness proliferation of dysplastic cells, loss of maturation and lack of cell polarity. Inflammatory cell infiltration of lymphocytes was observed in the upper dermis (Fig. 1b). The patient was diagnosed with BD. Considering the patient’s age and preference for non-surgical treatment, we attempted topical application of ingenol mebutate 0.05% gel with the institutional review board’s approval. We applied ingenol mebutate 0.05% gel on the affected area with a 0.5-cm margin once daily for 3 days consecutively. One day after the first application, we observed multiple vesicles overlying an erythematous background beyond the treated area. Local skin reactions including erythema, vesicles, erosion and ulceration, as well as a moderate degree of pain at the application site peaked between day 3 and 6. The ulceration was managed with daily wet dressing and hydrophilic polyurethane foam, and it healed completely with residual postinflammatory hyperpigmentation by day 12. Ten weeks after the treatment, all the lesions were clinically resolved (Fig. 1a); multiple skin punch biopsies showed no evidence of recurrent BD (Fig. 1b). At the time of writing this report (i.e. 6 months after the treatment), there has been no recurrence. Ingenol mebutate 5% gel is a new topical drug extracted from the latex sap of a plant, Euphorbia peplus, which has been used for centuries as a natural folk remedy for warts, corns and cancerous lesions.3 Clinical studies have proven it to be safe and efficacious, leading to the US Food and Drug Administration approval of this chemotherapeutic agent for field therapy of actinic keratosis in 2012. Topical ingenol mebutate gel was generally well tolerated in the treatment of patients with actinic keratoses, with the majority of adverse events being of mild to moderate severity including erythema, scaling, crusting, swelling, vesiculation/pustulation and erosion/ ulceration. Ingenol mebutate has a dual mode of action, facilitating cell necrosis, and on the other hand, producing antibod-
ies against the tumor, resulting in the destruction of dysplastic cells.4 Topical ingenol mebutate gel has begun to show effectiveness against superficial basal cell carcinoma.5 This is the first histologically proven case of BD successfully treated with ingenol mebutate 0.05% reported in the published work. We suggest that ingenol mebutate 0.05% gel could be a potentially effective and safe treatment option for BD, with a short treatment course, successful efficacy and cosmetic outcomes.
CONFLICT OF INTEREST: None declared. Joo Hee LEE, Ji Hae LEE, Jung Min BAE, Gyong Moon KIM Department of Dermatology, St Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea doi: 10.1111/1346-8138.12936
REFERENCES 1 Jaeger AB, Gramkow A, Hjalgrim H, Melbye M, Frisch M. Bowen disease and risk of subsequent malignant neoplasms: a populationbased cohort study of 1147 patients. Arch Dermatol 1999; 135: 790–793. 2 Bonerandi JJ, Beauvillain C, Caquant L et al. French Dermatology Recommendations Association (aRED): Guidelines for the diagnosis and treatment of cutaneous squamous cell carcinoma and precursor lesions. J Eur Acad Dermatol Venereol 2011; 25 (Suppl 5): 1–51. 3 Ramsay JR, Suhrbier A, Aylward JH et al. The sap from Euphorbia peplus is effective against human nonmelanoma skin cancers. Br J Dermatol 2011; 164(3): 633–636. 4 Rosen RH, Gupta AK, Tyring SK. Dual mechanism of action of ingenol mebutate gel for topical treatment of actinic keratoses: rapid lesion necrosis followed by lesionspecific immune response. J Am Acad Dermatol 2012; 66(3): 486–493. 5 Siller G, Rosen R, Freeman M, Welburn P, Katsamas J, Ogbourne SM. PEP005 (ingenol mebutate) gel for the topical treatment of superficial basal cell carcinoma: results of a randomized phase IIa trial. Australas J Dermatol 2010; 51: 99–105.
Diagnostically challenging case of low-fat spindle cell lipoma Dear Editor, Spindle cell lipoma (SCL) classically occurs as subcutaneous, masses in the upper trunk of older men and are composed of mature fat, CD34-positive spindle cells, ropey collagen and myxoid matrix.1 A number of variants have been reported. Billings et al. propose the terms “low-fat” and “fat-free” SCL in which fat was noted to be present in less than 5% of the tumor.2 These cases posed diagnostic difficulties because of the dearth of fat. A 41-year-old female presented with an asymptomatic nodule on her right neck, which was 40 mm in diameter (Fig. 1a).
The mass had been present for 20 years with no change in diameter. She had a history of schizophrenia. Magnetic resonance imaging showed a well-circumscribed nodule. Axial T1weighted (Fig. 1b) and T2-weighted imaging (Fig. 1c) showed a subcutaneous lesion with enhancement of the homogenous non-fatty components. Radiological diagnosis was fibroma or desmoid tumor. Histopathological findings showed that the tumor was well circumscribed and located in the subcutis. There was no connection with the epidermis. The stroma were collagen rich. The adipocytes comprised less than 5% of the tumor and were
Correspondence: Hidemi Nakagawa, M.D., Department of Dermatology, The Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461, Japan. Email: [email protected]
© 2015 Japanese Dermatological Association
921
Letters to the Editor
(a)
(b)
(c)
(d)
(e)
(f)
(g)
present in small clusters or as isolated, single adipocytes (Fig. 1d). The spindle cells were arrange in characteristic parallel arrays (Fig. 1e). The spindle cells were uniform, with a single elongated nucleus and narrow, bipolar cytoplasmic processes. Nucleoli were inconspicuous. Mitotic activity was not present. The stroma had wiry to ropey collagen (Fig. 1f). Immunohistochemical stains were performed and the spindle tumor cells were strongly positive for CD34 (Fig. 1g) and S-100, factor XIIIa, smooth muscle actin, desmin, CD99 and bcl-2 were negative. We diagnosed the patient with low-fat SCL. A female case of low-fat SCL is very rare. Low-fat SCL presents more commonly in older men (mean, 56 years; male : female ratio, 11:1) and as small (mean, 2.0 cm) circumscribed dermal or subcutaneous masses of the head/neck, back and shoulder.2 The tumors are composed of aggregates of CD34-positive, bland spindled cells arranged in characteristic parallel arrays, admixed with ropey collagen and myxoid matrix. Isolated clusters or single adipocytes are present. CD34 is diffusely positive. The most common benign entity in the differential diagnosis is neurofibroma. Neurofibroma is composed of spindle cells with comma-shaped nuclei and the stromal collagen is more delicate in neurofibroma. Although some admixed CD34-
922
Figure 1. (a) Clinical findings show an asymptomatic nodule on her right neck, with a diameter of 40 mm. (b,c) Magnetic resonance imaging show a well-circumscribed nodule on her right neck, with a diameter of 30 mm in diameter. Axial (b) T1- and (c) T2-weighted imaging showing a subcutaneous lesion with enhancement of the homogenous, non-fatty components. Radiological diagnosis was fibroma or desmoid tumor. (d) Histological findings show the tumor was well-circumscribed and located in the subcutis. The adipocytes comprised less than 5% of the tumor. The stroma were sclerotic or collagen rich. (e) The spindle tumor cells were arranged in characteristic parallel arrays (arrows). (f) The spindle cells were uniform, with a single elongated nucleus and narrow, bipolar cytoplasmic processes. Nucleoli were inconspicuous. The stroma had wiry to ropey collagen (arrows). (g) The spindle cells were strongly positive for CD34 (original magnification 9200). positive cells are frequently seen in neurofibroma, but S100 protein highlight the majority of the spindle cells. We should differentiate low-fat SCL from the CD34positive tumors such as solitary fibrous tumor. Solitary fibrous tumor shows a patternless architecture characterized by a combination of alternating hypo- and hypercellular areas separated from each other by thick bands of hyalinized collagen and branching hemangiopericytoma-like vessels. The tumor suppressor gene RB1, encoding the retinoblastoma (Rb) protein, is located at 13q14. Rb expression was deficient in all spindle cell lipomas, but solitary fibrous tumor was not.3 Low-fat SCL are rare and histologically frequently mistaken for other entities. It would be a diagnostically challenging case if one does not know about this entity.
CONFLICT OF INTEREST:
None.
Keigo ITO, Hidemi NAKAGAWA Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan doi: 10.1111/1346-8138.12947
© 2015 Japanese Dermatological Association
Letters to the Editor
REFERENCES 1 Enzinger FM, Harvey DA. Spindle cell lipoma. Cancer 1975; 36: 1852–1859. 2 Billings SD, Folpe AL. Diagnostically challenging spindle cell lipomas: a report of 34 “low-fat” and “fat-free” variants. Am J Dermatopathol 2007; 29: 437–442.
~o-Enrıquez A, Fletcher CD, Hornick JL. Loss of reti3 Chen BJ, Marin noblastoma protein expression in spindle cell/pleomorphic lipomas and cytogenetically related tumors: an immunohistochemcal study with diagnostic implications. Am J Surg Pathol 2012; 36: 1119– 1128.
Electron microscopic observation of cholesterotic fibrous histiocytoma of the finger Dear Editor, Cholesterotic fibrous histiocytoma (CFH) is a rare variant of dermatofibroma, which is characterized by deposits of cholesterol crystals within dermatofibroma.1 We herein report a case of CFH, describing the electron microscopic features for the first time. A 42-year-old man visited our department with a 2-year history of an asymptomatic tumor on the dorsum of the proximal phalanx of left ring finger. Physical examination revealed a solitary brownish firm tumor, 8 mm in diameter (Fig. 1a). Although he had a history of mild hyperlipidemia, laboratory
findings at presentation were within normal limits. The tumor was clinically suspected as dermatofibroma, and an excisional biopsy was performed. Histopathological examination revealed symmetrical nodular proliferation of fibroblast-like and histiocyte-like cells in the entire dermis with occasional storiform arrangements. In the center of the tumor, there were needle spindle-shaped cholesterol crystals surrounded by cells with foamy cytoplasm (Fig. 1b–d). Immunohistochemistry showed accumulation of CD68-positive cells at the periphery of the crystals in the center of the tumor (Fig. 1e). Fibrohistiocytic tumor cells and foam cells were vimentin positive and CD34
(a)
(d) Figure 1. (a) Skin lesion on the dorsum of left ring finger. (b) Symmetrical proliferation of fibrohistiocytic tumor cells in the dermis (hematoxylin–eosin [HE], loupe view). (c) Proliferation of fibroblast-like and histiocyte-like cells (HE, original magnification 9100). (d) Cholesterol crystals surrounded by foam cells in the center of the tumor (HE, 9200). (e) CD68-positive cells around cholesterol crystals (9200). (f) Histiocyte (H) is closely attached to large cholesterol crystals (C). Small, thin cholesterol crystals (yellow arrows) and variously sized dense, amorphous lysosomes (L) containing spherical, translucent vacuoles thought to be lipid droplets are seen in the cell (94,000). (g) In higher magnification view, thin cholesterol crystals (arrows) are observed at the periphery of lysosomes (L) in histiocyte contact with large cholesterol crystals (C) (912,000).
(b)
(e)
(c)
(f)
(g)
Correspondence: Koremasa Hayama, M.D., Ph.D., Division of Cutaneous Science, Department of Dermatology, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan. Email: [email protected]
© 2015 Japanese Dermatological Association
923
tous plaque measuring 3 cm 9 1.8 cm was observed on the right calf (Fig. 1a). Histopathology showed hyperkeratosis and marked acanthosis with full-thickness proliferation of dysplastic cells, loss of maturation and lack of cell polarity. Inflammatory cell infiltration of lymphocytes was observed in the upper dermis (Fig. 1b). The patient was diagnosed with BD. Considering the patient’s age and preference for non-surgical treatment, we attempted topical application of ingenol mebutate 0.05% gel with the institutional review board’s approval. We applied ingenol mebutate 0.05% gel on the affected area with a 0.5-cm margin once daily for 3 days consecutively. One day after the first application, we observed multiple vesicles overlying an erythematous background beyond the treated area. Local skin reactions including erythema, vesicles, erosion and ulceration, as well as a moderate degree of pain at the application site peaked between day 3 and 6. The ulceration was managed with daily wet dressing and hydrophilic polyurethane foam, and it healed completely with residual postinflammatory hyperpigmentation by day 12. Ten weeks after the treatment, all the lesions were clinically resolved (Fig. 1a); multiple skin punch biopsies showed no evidence of recurrent BD (Fig. 1b). At the time of writing this report (i.e. 6 months after the treatment), there has been no recurrence. Ingenol mebutate 5% gel is a new topical drug extracted from the latex sap of a plant, Euphorbia peplus, which has been used for centuries as a natural folk remedy for warts, corns and cancerous lesions.3 Clinical studies have proven it to be safe and efficacious, leading to the US Food and Drug Administration approval of this chemotherapeutic agent for field therapy of actinic keratosis in 2012. Topical ingenol mebutate gel was generally well tolerated in the treatment of patients with actinic keratoses, with the majority of adverse events being of mild to moderate severity including erythema, scaling, crusting, swelling, vesiculation/pustulation and erosion/ ulceration. Ingenol mebutate has a dual mode of action, facilitating cell necrosis, and on the other hand, producing antibod-
ies against the tumor, resulting in the destruction of dysplastic cells.4 Topical ingenol mebutate gel has begun to show effectiveness against superficial basal cell carcinoma.5 This is the first histologically proven case of BD successfully treated with ingenol mebutate 0.05% reported in the published work. We suggest that ingenol mebutate 0.05% gel could be a potentially effective and safe treatment option for BD, with a short treatment course, successful efficacy and cosmetic outcomes.
CONFLICT OF INTEREST: None declared. Joo Hee LEE, Ji Hae LEE, Jung Min BAE, Gyong Moon KIM Department of Dermatology, St Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea doi: 10.1111/1346-8138.12936
REFERENCES 1 Jaeger AB, Gramkow A, Hjalgrim H, Melbye M, Frisch M. Bowen disease and risk of subsequent malignant neoplasms: a populationbased cohort study of 1147 patients. Arch Dermatol 1999; 135: 790–793. 2 Bonerandi JJ, Beauvillain C, Caquant L et al. French Dermatology Recommendations Association (aRED): Guidelines for the diagnosis and treatment of cutaneous squamous cell carcinoma and precursor lesions. J Eur Acad Dermatol Venereol 2011; 25 (Suppl 5): 1–51. 3 Ramsay JR, Suhrbier A, Aylward JH et al. The sap from Euphorbia peplus is effective against human nonmelanoma skin cancers. Br J Dermatol 2011; 164(3): 633–636. 4 Rosen RH, Gupta AK, Tyring SK. Dual mechanism of action of ingenol mebutate gel for topical treatment of actinic keratoses: rapid lesion necrosis followed by lesionspecific immune response. J Am Acad Dermatol 2012; 66(3): 486–493. 5 Siller G, Rosen R, Freeman M, Welburn P, Katsamas J, Ogbourne SM. PEP005 (ingenol mebutate) gel for the topical treatment of superficial basal cell carcinoma: results of a randomized phase IIa trial. Australas J Dermatol 2010; 51: 99–105.
Diagnostically challenging case of low-fat spindle cell lipoma Dear Editor, Spindle cell lipoma (SCL) classically occurs as subcutaneous, masses in the upper trunk of older men and are composed of mature fat, CD34-positive spindle cells, ropey collagen and myxoid matrix.1 A number of variants have been reported. Billings et al. propose the terms “low-fat” and “fat-free” SCL in which fat was noted to be present in less than 5% of the tumor.2 These cases posed diagnostic difficulties because of the dearth of fat. A 41-year-old female presented with an asymptomatic nodule on her right neck, which was 40 mm in diameter (Fig. 1a).
The mass had been present for 20 years with no change in diameter. She had a history of schizophrenia. Magnetic resonance imaging showed a well-circumscribed nodule. Axial T1weighted (Fig. 1b) and T2-weighted imaging (Fig. 1c) showed a subcutaneous lesion with enhancement of the homogenous non-fatty components. Radiological diagnosis was fibroma or desmoid tumor. Histopathological findings showed that the tumor was well circumscribed and located in the subcutis. There was no connection with the epidermis. The stroma were collagen rich. The adipocytes comprised less than 5% of the tumor and were
Correspondence: Hidemi Nakagawa, M.D., Department of Dermatology, The Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461, Japan. Email: [email protected]
© 2015 Japanese Dermatological Association
921
Letters to the Editor
(a)
(b)
(c)
(d)
(e)
(f)
(g)
present in small clusters or as isolated, single adipocytes (Fig. 1d). The spindle cells were arrange in characteristic parallel arrays (Fig. 1e). The spindle cells were uniform, with a single elongated nucleus and narrow, bipolar cytoplasmic processes. Nucleoli were inconspicuous. Mitotic activity was not present. The stroma had wiry to ropey collagen (Fig. 1f). Immunohistochemical stains were performed and the spindle tumor cells were strongly positive for CD34 (Fig. 1g) and S-100, factor XIIIa, smooth muscle actin, desmin, CD99 and bcl-2 were negative. We diagnosed the patient with low-fat SCL. A female case of low-fat SCL is very rare. Low-fat SCL presents more commonly in older men (mean, 56 years; male : female ratio, 11:1) and as small (mean, 2.0 cm) circumscribed dermal or subcutaneous masses of the head/neck, back and shoulder.2 The tumors are composed of aggregates of CD34-positive, bland spindled cells arranged in characteristic parallel arrays, admixed with ropey collagen and myxoid matrix. Isolated clusters or single adipocytes are present. CD34 is diffusely positive. The most common benign entity in the differential diagnosis is neurofibroma. Neurofibroma is composed of spindle cells with comma-shaped nuclei and the stromal collagen is more delicate in neurofibroma. Although some admixed CD34-
922
Figure 1. (a) Clinical findings show an asymptomatic nodule on her right neck, with a diameter of 40 mm. (b,c) Magnetic resonance imaging show a well-circumscribed nodule on her right neck, with a diameter of 30 mm in diameter. Axial (b) T1- and (c) T2-weighted imaging showing a subcutaneous lesion with enhancement of the homogenous, non-fatty components. Radiological diagnosis was fibroma or desmoid tumor. (d) Histological findings show the tumor was well-circumscribed and located in the subcutis. The adipocytes comprised less than 5% of the tumor. The stroma were sclerotic or collagen rich. (e) The spindle tumor cells were arranged in characteristic parallel arrays (arrows). (f) The spindle cells were uniform, with a single elongated nucleus and narrow, bipolar cytoplasmic processes. Nucleoli were inconspicuous. The stroma had wiry to ropey collagen (arrows). (g) The spindle cells were strongly positive for CD34 (original magnification 9200). positive cells are frequently seen in neurofibroma, but S100 protein highlight the majority of the spindle cells. We should differentiate low-fat SCL from the CD34positive tumors such as solitary fibrous tumor. Solitary fibrous tumor shows a patternless architecture characterized by a combination of alternating hypo- and hypercellular areas separated from each other by thick bands of hyalinized collagen and branching hemangiopericytoma-like vessels. The tumor suppressor gene RB1, encoding the retinoblastoma (Rb) protein, is located at 13q14. Rb expression was deficient in all spindle cell lipomas, but solitary fibrous tumor was not.3 Low-fat SCL are rare and histologically frequently mistaken for other entities. It would be a diagnostically challenging case if one does not know about this entity.
CONFLICT OF INTEREST:
None.
Keigo ITO, Hidemi NAKAGAWA Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan doi: 10.1111/1346-8138.12947
© 2015 Japanese Dermatological Association
Letters to the Editor
REFERENCES 1 Enzinger FM, Harvey DA. Spindle cell lipoma. Cancer 1975; 36: 1852–1859. 2 Billings SD, Folpe AL. Diagnostically challenging spindle cell lipomas: a report of 34 “low-fat” and “fat-free” variants. Am J Dermatopathol 2007; 29: 437–442.
~o-Enrıquez A, Fletcher CD, Hornick JL. Loss of reti3 Chen BJ, Marin noblastoma protein expression in spindle cell/pleomorphic lipomas and cytogenetically related tumors: an immunohistochemcal study with diagnostic implications. Am J Surg Pathol 2012; 36: 1119– 1128.
Electron microscopic observation of cholesterotic fibrous histiocytoma of the finger Dear Editor, Cholesterotic fibrous histiocytoma (CFH) is a rare variant of dermatofibroma, which is characterized by deposits of cholesterol crystals within dermatofibroma.1 We herein report a case of CFH, describing the electron microscopic features for the first time. A 42-year-old man visited our department with a 2-year history of an asymptomatic tumor on the dorsum of the proximal phalanx of left ring finger. Physical examination revealed a solitary brownish firm tumor, 8 mm in diameter (Fig. 1a). Although he had a history of mild hyperlipidemia, laboratory
findings at presentation were within normal limits. The tumor was clinically suspected as dermatofibroma, and an excisional biopsy was performed. Histopathological examination revealed symmetrical nodular proliferation of fibroblast-like and histiocyte-like cells in the entire dermis with occasional storiform arrangements. In the center of the tumor, there were needle spindle-shaped cholesterol crystals surrounded by cells with foamy cytoplasm (Fig. 1b–d). Immunohistochemistry showed accumulation of CD68-positive cells at the periphery of the crystals in the center of the tumor (Fig. 1e). Fibrohistiocytic tumor cells and foam cells were vimentin positive and CD34
(a)
(d) Figure 1. (a) Skin lesion on the dorsum of left ring finger. (b) Symmetrical proliferation of fibrohistiocytic tumor cells in the dermis (hematoxylin–eosin [HE], loupe view). (c) Proliferation of fibroblast-like and histiocyte-like cells (HE, original magnification 9100). (d) Cholesterol crystals surrounded by foam cells in the center of the tumor (HE, 9200). (e) CD68-positive cells around cholesterol crystals (9200). (f) Histiocyte (H) is closely attached to large cholesterol crystals (C). Small, thin cholesterol crystals (yellow arrows) and variously sized dense, amorphous lysosomes (L) containing spherical, translucent vacuoles thought to be lipid droplets are seen in the cell (94,000). (g) In higher magnification view, thin cholesterol crystals (arrows) are observed at the periphery of lysosomes (L) in histiocyte contact with large cholesterol crystals (C) (912,000).
(b)
(e)
(c)
(f)
(g)
Correspondence: Koremasa Hayama, M.D., Ph.D., Division of Cutaneous Science, Department of Dermatology, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan. Email: [email protected]
© 2015 Japanese Dermatological Association
923
