Letters to the Editor
2056
inhibitors such as infliximab, because TNF-a plays a major role in the immunopathogenesis of GPP caused by DITRA. In conclusion, Viguier’s cases and our cases suggest that TNFa inhibitors are powerful tools for treating GPP caused by DITRA. K. Sugiura,1,* K. Endo,2 T. Akasaka,2 M. Akiyama1 1
Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan, 2Department of Dermatology, Iwate Medical University, Morioka, Japan *Correspondence: K. Sugiura. E-mail: [email protected]
References 1 Viguier M, Aubin F, Delaporte E et al. Efficacy and safety of tumor necrosis factor inhibitors in acute generalized pustular psoriasis. Arch Dermatol 2012; 148: 1423–1425. 2 Sugiura K, Takemoto A, Yamaguchi M et al. The Majority of Generalized Pustular Psoriasis without Psoriasis Vulgaris Is Caused by Deficiency of Interleukin-36 Receptor Antagonist. J Invest Dermatol 2013; 133: 2514– 2521. 3 Marrakchi S, Guigue P, Renshaw BR et al. Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. N Engl J Med 2011; 365: 620–628. 4 Cowen EW, Goldbach-Mansky R. DIRA, DITRA, and new insights into pathways of skin inflammation: what’s in a name? Arch Dermatol 2012; 148: 381–384. 5 Carrier Y, Ma HL, Ramon HE et al. Inter-regulation of Th17 cytokines and the IL-36 cytokines in vitro and in vivo: implications in psoriasis pathogenesis. J Invest Dermatol 2011; 131: 2428–2437. DOI: 10.1111/jdv.12590
Cutaneous squamous cell carcinoma with osteoclast-like giant cells: a very rare variant of cutaneous squamous cell carcinoma Editor An 89 year-old female presented to us with an asymptomatic ulcerated multinodular tumour on the left temple which had grown over the past 6 months. On clinical examination, a 3 cmsized erythematous, ulcerated, multinodular tumour was seen on the left temple. With the clinical suspicion of squamous cell carcinoma (SCC) complete excision for histologic examination was performed. On H&E staining, a deeply infiltrating multinodular tumour consisting of two components was seen. One component was a moderately-differentiated, keratinizing, cutaneous SCC with deep dermal infiltration (Fig. 1a,b). Surrounding the infiltrating strands of carcinoma cells, there was a mixed inflammatory
JEADV 2015, 29, 2051–2065
infiltration consisting of lymphocytes, several eosinophils and numerous, partly bizarre osteoclast-like giant cells (OLGCs) (Fig. 1c). Most OLGCs were located in close proximity to the epithelial strands and contained up to 40 nuclei. Some OLGCs showed eosinophilic inclusions. On immunohistochemistry (IHC), the SCC was positive for Pan-Cytokeratin (AE1/3) and p63. OLGCs were negative for p63 and Pan-Cytokeratin except for some intracellular inclusions which were positive for PanCytokeratin (Fig. 2c,d). In contrast, CD68 was strongly expressed by OLGCs, but not by SCC cells (Fig. 2a,b). Thus, the diagnosis of cutaneous SCC with OLGC was made. After complete excision, wound closure was achieved with a split-skin graft. On clinical examination and sonography of cervical lymph nodes, there was no evidence of metastatic spread. Thus, regular follow-up according to the guidelines for cutaneous SCC was recommended. OLGCs have been described to occur in rare variants of diverse extraosseous, visceral, usually moderately- to poorly differentiated malignant tumours. Cutaneous malignant tumours with infiltration of OLGCs are extremely rare. In the literature, OLGCs were first reported in a malignant melanoma in 20051 and in a cutaneous SCC in 2007.2 Overall, up to now only six cases of cutaneous SCC and three cases of malignant melanoma with OLGCs have been reported.3–6 In the majority of cases, it is assumed that OLGCs are rather a reactive component as they show a markedly different pattern of marker expression as compared to the neoplastic component. However, it cannot be excluded that OLGCs derive from the neoplastic cells in certain cases of cutaneous malignant tumours. In contrast to our case most SCCs with OLGCs that have been reported so far were rather poorly differentiated or even sarcomatoid potentially leading to the misdiagnosis of atypical fibroxanthoma (AFX) which was reported for two cases.4 IHC for p63, cytokeratins (AE1/3, CK5/6), CD99 and CD10 can be helpful in distinguishing AFX from SCC with OLGCs. Furthermore, discrimination from other OLGC-containing conditions is important. Benign examples are nodular fasciitis, dermatofibroma, giant cell tumour of tendon sheath and phosphaturic mesenchymal tumour. Malignant examples comprise soft tissue giant cell tumour of low malignant potential (STGCT-LMP), giant cell malignant fibrous histiocytoma (GC-MFH), plexiform fibriohistiocytiy tumour, leiomyosarcoma with giant cells and AFX. Phenotypic and molecular studies suggest that OLGCs in STGCT-LMP and GC-MFH indeed derive from the neoplastic component and in these tumours the cells demonstrate osteoclast differentiation.7 The mechanisms underlying OLGC infiltration in malignant melanoma and SCC are unknown. It may be hypothesized that cytokines or growth factors that are secreted by tumour cells are involved. As a heavy inflammatory infiltration of lymphocytes and eosinophils was seen besides the OLGCs in our case a pathogenic relationship with lympoepithelioma-like carcinoma might exist. In this tumour, a combination
© 2014 European Academy of Dermatology and Venereology
Letters to the Editor
2057
(a)
(b)
(c)
(d)
(a)
(b)
(c)
(d)
Figure 1 H&E staining: (a) Low-power view of an ulcerated carcinoma with infiltrating growth pattern (20-x). (b) keratinizing strands of pleomorphic epithelial cells with surrounding inflammatory infiltration (200-x), (c) und (d) High-power viewl of osteoclastlike giant cells with 20–40 nuclei and phagocytosed eosinophilic inclusions (400-x).
Figure 2 Immunhistochemistry: (a,b) numerous CD68-positive multinucleated giant cells (a 40-x, b 200-x), (c,d) PanCytokeratin (AE1/3) positive strands of carcinoma cells and negative giant cells (c 100-x, d 200-x).
of a lymphomatoid inflammatory reaction is seen in conjunction with a SCC without OLGCs. The pathogenesis of lymphoepithelioma-like carcinoma, however, is also unknown. In summary, OLGC-containing tumours are rarely seen in the skin. However, knowledge of the differential diagnosis and proper classification of OLGC-containing tumours is of great importance as malignant potential and prognosis widely differ between these tumours.
JEADV 2015, 29, 2051–2065
raud,1,* A. Marx,2 S. Goerdt1 C. Ge 1
Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany, 2Department of Pathology, University Medical Center and Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany raud. E-mail: [email protected] *Correspondence: C. Ge
© 2014 European Academy of Dermatology and Venereology
2058
Letters to the Editor
References 1 Al-Brahim N, Salama S. Malignant melanoma with osteoclast-like giant cells: an unusual host response: immunohistochemical and ultrastructural study of three cases and literature review. Am J Dermatopathol 2005; 27: 126–129. 2 Emanuel PO, Shim H, Phelps RG. Poorly differentiated squamous cell carcinoma with osteoclastic giant-cell-like proliferation. J Cutan Pathol 2007; 34: 930–933. 3 Yozu M, Glengarry J, Ahmed SS. Cutaneous squamous cell carcinoma associated with proliferation of osteoclast-like giant cells. J Pak Med Assoc 2011; 61: 922–925. 4 Beer TW. Squamous cell carcinoma with osteoclast-like giant cells: 2 cases misdiagnosed as atypical fibroxanthoma. Am J Dermatopathol 2010; 32: 414–415. 5 Wooff J, Werner D, Murphy J, Walsh N. Osteoclast-like giant cell reaction associated with cutaneous squamous cell carcinoma: a report of 2 cases and review of the literature. Am J Dermatopathol 2009; 31: 282–287. 6 Emanuel P. Osteoclast-type giant cells accompanying cutaneous squamous cell carcinoma. Am J Dermatopathol 2009; 31: 96. 7 Lau YS, Sabokbar A, Gibbons CL, Giele H, Athanasou N. Phenotypic and molecular studies of giant-cell tumors of bone and soft tissue. Hum Pathol 2005; 36: 945–954. DOI: 10.1111/jdv.12592
Figure 1 Bilateral, symmetrical, sharply demarcated brown pigmentation extending from the posterior side of both thighs down to the ankles.
Pigmentary demarcation lines of pregnancy in two Caucasian women Editor A 33-year-old Caucasian primigravida woman presented with asymptomatic brown pigmentation with sharp borders on the back of lower extremities, which appeared during the ninth month of her pregnancy and started to fade after delivery. The family history was unremarkable for pigmentary disorders and she was otherwise healthy. Dermatological examination revealed bilateral, symmetrical, brown patches extending from the posterior side of both thighs down to the ankles, which were clearly demarcated from the normally pigmented skin (Fig. 1). The diagnosis of pigmentary demarcation lines (PDLs) of pregnancy was made. Within 3 months, the pigmentation disappeared spontaneously. After 2 months, a second patient, a 32-year-old Caucasian primigravida woman who gave birth 4 months ago, was admitted to our dermatology department. She presented with asymptomatic brown pigmentation on the posterior areas of her thighs and legs which she had first noticed in the eighth month of her pregnancy. On dermatological examination, bilateral, symmetrical, brown patches involving the posterior side of both thighs down to ankles, which had clear boundaries with the adjacent normal skin was noted. She was diagnosed with PDLs of pregnancy. During the next 2 months, the pigmentation faded spontaneously.
JEADV 2015, 29, 2051–2065
Pigmentary demarcation lines, also called Futcher or Voigt lines, are borders of abrupt transition between more deeply pigmented skin and lighter pigmentation. Those lines correspond with Voigt lines and are thought to result from differences in melanocyte distribution.1 Matsumoto was the first who described pigmentary demarcation lines in a case series of Japanese women in 1913.2 Since this original description, based on different localizations, eight different types (A–H) have been reported.3 Type B is usually associated with pregnancy and involves the posteromedial area of lower extremities. The pigmentation usually appears during the third trimester of pregnancy, follows a benign course, and fades spontaneously within 1–7 months in the postpartum period. The aetiology is unknown, however, increase in melanocyte-stimulating hormone during pregnancy is suspected to trigger clinically inconspicuous melanocyte-specific peripheral nerve areas, which in turn gives rise to hyperpigmentation of specific skin zones.1 The role of other pregnancy-related hormonal alterations regarding oestrogens and progesterone is supported by the report of a non-pregnant woman with type B PDLs who received oestrogenic medication.4 It is also proposed that, compression of peripheral nerves rooting from S1 and S2 levels by the enlarged uterus due to pregnancy and obstruction of the innervated cutaneous vasculature induce the resultant pigmentation.5 The diagnosis mostly depends on the clinical findings and histopathological examination is seldom required.
© 2014 European Academy of Dermatology and Venereology
2056
inhibitors such as infliximab, because TNF-a plays a major role in the immunopathogenesis of GPP caused by DITRA. In conclusion, Viguier’s cases and our cases suggest that TNFa inhibitors are powerful tools for treating GPP caused by DITRA. K. Sugiura,1,* K. Endo,2 T. Akasaka,2 M. Akiyama1 1
Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan, 2Department of Dermatology, Iwate Medical University, Morioka, Japan *Correspondence: K. Sugiura. E-mail: [email protected]
References 1 Viguier M, Aubin F, Delaporte E et al. Efficacy and safety of tumor necrosis factor inhibitors in acute generalized pustular psoriasis. Arch Dermatol 2012; 148: 1423–1425. 2 Sugiura K, Takemoto A, Yamaguchi M et al. The Majority of Generalized Pustular Psoriasis without Psoriasis Vulgaris Is Caused by Deficiency of Interleukin-36 Receptor Antagonist. J Invest Dermatol 2013; 133: 2514– 2521. 3 Marrakchi S, Guigue P, Renshaw BR et al. Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. N Engl J Med 2011; 365: 620–628. 4 Cowen EW, Goldbach-Mansky R. DIRA, DITRA, and new insights into pathways of skin inflammation: what’s in a name? Arch Dermatol 2012; 148: 381–384. 5 Carrier Y, Ma HL, Ramon HE et al. Inter-regulation of Th17 cytokines and the IL-36 cytokines in vitro and in vivo: implications in psoriasis pathogenesis. J Invest Dermatol 2011; 131: 2428–2437. DOI: 10.1111/jdv.12590
Cutaneous squamous cell carcinoma with osteoclast-like giant cells: a very rare variant of cutaneous squamous cell carcinoma Editor An 89 year-old female presented to us with an asymptomatic ulcerated multinodular tumour on the left temple which had grown over the past 6 months. On clinical examination, a 3 cmsized erythematous, ulcerated, multinodular tumour was seen on the left temple. With the clinical suspicion of squamous cell carcinoma (SCC) complete excision for histologic examination was performed. On H&E staining, a deeply infiltrating multinodular tumour consisting of two components was seen. One component was a moderately-differentiated, keratinizing, cutaneous SCC with deep dermal infiltration (Fig. 1a,b). Surrounding the infiltrating strands of carcinoma cells, there was a mixed inflammatory
JEADV 2015, 29, 2051–2065
infiltration consisting of lymphocytes, several eosinophils and numerous, partly bizarre osteoclast-like giant cells (OLGCs) (Fig. 1c). Most OLGCs were located in close proximity to the epithelial strands and contained up to 40 nuclei. Some OLGCs showed eosinophilic inclusions. On immunohistochemistry (IHC), the SCC was positive for Pan-Cytokeratin (AE1/3) and p63. OLGCs were negative for p63 and Pan-Cytokeratin except for some intracellular inclusions which were positive for PanCytokeratin (Fig. 2c,d). In contrast, CD68 was strongly expressed by OLGCs, but not by SCC cells (Fig. 2a,b). Thus, the diagnosis of cutaneous SCC with OLGC was made. After complete excision, wound closure was achieved with a split-skin graft. On clinical examination and sonography of cervical lymph nodes, there was no evidence of metastatic spread. Thus, regular follow-up according to the guidelines for cutaneous SCC was recommended. OLGCs have been described to occur in rare variants of diverse extraosseous, visceral, usually moderately- to poorly differentiated malignant tumours. Cutaneous malignant tumours with infiltration of OLGCs are extremely rare. In the literature, OLGCs were first reported in a malignant melanoma in 20051 and in a cutaneous SCC in 2007.2 Overall, up to now only six cases of cutaneous SCC and three cases of malignant melanoma with OLGCs have been reported.3–6 In the majority of cases, it is assumed that OLGCs are rather a reactive component as they show a markedly different pattern of marker expression as compared to the neoplastic component. However, it cannot be excluded that OLGCs derive from the neoplastic cells in certain cases of cutaneous malignant tumours. In contrast to our case most SCCs with OLGCs that have been reported so far were rather poorly differentiated or even sarcomatoid potentially leading to the misdiagnosis of atypical fibroxanthoma (AFX) which was reported for two cases.4 IHC for p63, cytokeratins (AE1/3, CK5/6), CD99 and CD10 can be helpful in distinguishing AFX from SCC with OLGCs. Furthermore, discrimination from other OLGC-containing conditions is important. Benign examples are nodular fasciitis, dermatofibroma, giant cell tumour of tendon sheath and phosphaturic mesenchymal tumour. Malignant examples comprise soft tissue giant cell tumour of low malignant potential (STGCT-LMP), giant cell malignant fibrous histiocytoma (GC-MFH), plexiform fibriohistiocytiy tumour, leiomyosarcoma with giant cells and AFX. Phenotypic and molecular studies suggest that OLGCs in STGCT-LMP and GC-MFH indeed derive from the neoplastic component and in these tumours the cells demonstrate osteoclast differentiation.7 The mechanisms underlying OLGC infiltration in malignant melanoma and SCC are unknown. It may be hypothesized that cytokines or growth factors that are secreted by tumour cells are involved. As a heavy inflammatory infiltration of lymphocytes and eosinophils was seen besides the OLGCs in our case a pathogenic relationship with lympoepithelioma-like carcinoma might exist. In this tumour, a combination
© 2014 European Academy of Dermatology and Venereology
Letters to the Editor
2057
(a)
(b)
(c)
(d)
(a)
(b)
(c)
(d)
Figure 1 H&E staining: (a) Low-power view of an ulcerated carcinoma with infiltrating growth pattern (20-x). (b) keratinizing strands of pleomorphic epithelial cells with surrounding inflammatory infiltration (200-x), (c) und (d) High-power viewl of osteoclastlike giant cells with 20–40 nuclei and phagocytosed eosinophilic inclusions (400-x).
Figure 2 Immunhistochemistry: (a,b) numerous CD68-positive multinucleated giant cells (a 40-x, b 200-x), (c,d) PanCytokeratin (AE1/3) positive strands of carcinoma cells and negative giant cells (c 100-x, d 200-x).
of a lymphomatoid inflammatory reaction is seen in conjunction with a SCC without OLGCs. The pathogenesis of lymphoepithelioma-like carcinoma, however, is also unknown. In summary, OLGC-containing tumours are rarely seen in the skin. However, knowledge of the differential diagnosis and proper classification of OLGC-containing tumours is of great importance as malignant potential and prognosis widely differ between these tumours.
JEADV 2015, 29, 2051–2065
raud,1,* A. Marx,2 S. Goerdt1 C. Ge 1
Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany, 2Department of Pathology, University Medical Center and Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany raud. E-mail: [email protected] *Correspondence: C. Ge
© 2014 European Academy of Dermatology and Venereology
2058
Letters to the Editor
References 1 Al-Brahim N, Salama S. Malignant melanoma with osteoclast-like giant cells: an unusual host response: immunohistochemical and ultrastructural study of three cases and literature review. Am J Dermatopathol 2005; 27: 126–129. 2 Emanuel PO, Shim H, Phelps RG. Poorly differentiated squamous cell carcinoma with osteoclastic giant-cell-like proliferation. J Cutan Pathol 2007; 34: 930–933. 3 Yozu M, Glengarry J, Ahmed SS. Cutaneous squamous cell carcinoma associated with proliferation of osteoclast-like giant cells. J Pak Med Assoc 2011; 61: 922–925. 4 Beer TW. Squamous cell carcinoma with osteoclast-like giant cells: 2 cases misdiagnosed as atypical fibroxanthoma. Am J Dermatopathol 2010; 32: 414–415. 5 Wooff J, Werner D, Murphy J, Walsh N. Osteoclast-like giant cell reaction associated with cutaneous squamous cell carcinoma: a report of 2 cases and review of the literature. Am J Dermatopathol 2009; 31: 282–287. 6 Emanuel P. Osteoclast-type giant cells accompanying cutaneous squamous cell carcinoma. Am J Dermatopathol 2009; 31: 96. 7 Lau YS, Sabokbar A, Gibbons CL, Giele H, Athanasou N. Phenotypic and molecular studies of giant-cell tumors of bone and soft tissue. Hum Pathol 2005; 36: 945–954. DOI: 10.1111/jdv.12592
Figure 1 Bilateral, symmetrical, sharply demarcated brown pigmentation extending from the posterior side of both thighs down to the ankles.
Pigmentary demarcation lines of pregnancy in two Caucasian women Editor A 33-year-old Caucasian primigravida woman presented with asymptomatic brown pigmentation with sharp borders on the back of lower extremities, which appeared during the ninth month of her pregnancy and started to fade after delivery. The family history was unremarkable for pigmentary disorders and she was otherwise healthy. Dermatological examination revealed bilateral, symmetrical, brown patches extending from the posterior side of both thighs down to the ankles, which were clearly demarcated from the normally pigmented skin (Fig. 1). The diagnosis of pigmentary demarcation lines (PDLs) of pregnancy was made. Within 3 months, the pigmentation disappeared spontaneously. After 2 months, a second patient, a 32-year-old Caucasian primigravida woman who gave birth 4 months ago, was admitted to our dermatology department. She presented with asymptomatic brown pigmentation on the posterior areas of her thighs and legs which she had first noticed in the eighth month of her pregnancy. On dermatological examination, bilateral, symmetrical, brown patches involving the posterior side of both thighs down to ankles, which had clear boundaries with the adjacent normal skin was noted. She was diagnosed with PDLs of pregnancy. During the next 2 months, the pigmentation faded spontaneously.
JEADV 2015, 29, 2051–2065
Pigmentary demarcation lines, also called Futcher or Voigt lines, are borders of abrupt transition between more deeply pigmented skin and lighter pigmentation. Those lines correspond with Voigt lines and are thought to result from differences in melanocyte distribution.1 Matsumoto was the first who described pigmentary demarcation lines in a case series of Japanese women in 1913.2 Since this original description, based on different localizations, eight different types (A–H) have been reported.3 Type B is usually associated with pregnancy and involves the posteromedial area of lower extremities. The pigmentation usually appears during the third trimester of pregnancy, follows a benign course, and fades spontaneously within 1–7 months in the postpartum period. The aetiology is unknown, however, increase in melanocyte-stimulating hormone during pregnancy is suspected to trigger clinically inconspicuous melanocyte-specific peripheral nerve areas, which in turn gives rise to hyperpigmentation of specific skin zones.1 The role of other pregnancy-related hormonal alterations regarding oestrogens and progesterone is supported by the report of a non-pregnant woman with type B PDLs who received oestrogenic medication.4 It is also proposed that, compression of peripheral nerves rooting from S1 and S2 levels by the enlarged uterus due to pregnancy and obstruction of the innervated cutaneous vasculature induce the resultant pigmentation.5 The diagnosis mostly depends on the clinical findings and histopathological examination is seldom required.
© 2014 European Academy of Dermatology and Venereology
