- Email: [email protected]
Skin involvement in T-cell prolymphocytic leukemia
J AM ACAD DERMATOL
Letters 533
VOLUME 57, NUMBER 3
therapy (HT) and estrogen therapy (ET).2 The North American Menopause Society recommends using HT as a general term encompassing the more specific terms ET for estrogen therapy and EPT for estrogen/ progestin therapy.3 As our knowledge becomes more sophisticated, other subtleties in terminology emerge. Historically, various synthetic or equine estradiol analogs (estrogens) were considered functionally identical to estradiol and to each other and the terms were often used interchangeably. Both the Food and Drug Administration and North American Menopause Society still state that until reliable evidence proves otherwise, we must assume that the risks and benefits of all estrogens are the same.2,3 However, accumulating evidence makes it clear that conjugated equine estrogens (Premarin) and synthetic analogs (ethinyl estradiol, esterified estrogens) differ from the predominant human hormone, estradiol, and from each other.4,5 Effects vary in different tissues, presumably because of the variable receptor affinity for slightly different molecules. Hall and Phillips attempted valiantly to differentiate among the estrogens, employing the different terms used in the various references they reviewed. Unfortunately, research in this area has progressed with great confusion of terms, measurements, baselines, doses, delivery systems, and regimens. We should not be surprised to find conflicting results and conclusions. When we review the literature of female hormone science, our challenge is not only to identify estrogen’s effects, but to understand how the effects differ with the different estrogen analogs. Valori Treloar, MD Integrative Dermatology, PC Funding sources: None. Conflicts of interest: None declared. Correspondence to: Valori Treloar, MD, Integrative Dermatology, PC, 1172 Beacon St, Suite 402, Newton, MA 02461 REFERENCES 1. Hall G, Phillips TJ. Estrogen and skin: the effects of estrogen, menopause, and hormone replacement therapy on the skin. J Am Acad Dermatol 2005;53:555-68. 2. FDA Docket No. 03D-0007. Draft guidance for industry on estrogen and estrogen/progestin drug products to treat vasomotor symptoms and vulvar and vaginal atrophy symptomse Recommendations for clinical evaluation; availability. Margaret M. Dotzel, Assistance Commissioner for Policy, Health and Human Services. January 23, 2003. 3. Menopause practice: a clinician’s guide. Cleveland (OH): The North American Menopause Society; 2004. p. 113.
4. Smith NL, Heckbert SR, Lemaitre RN, Reiner AP, Lumley T, Weiss NS, et al. Esterified estrogens and conjugated equine estrogens and the risk of venous thrombosis. JAMA 2004;292:1581-7. 5. Leng XH, Zhang W, Nieswandt B, Bray PF. Effects of estrogen replacement therapies on mouse platelet function and glycoprotein VI levels. Circ Res 2005;97:415-7. doi:10.1016/j.jaad.2006.02.048
Skin involvement in T-cell prolymphocytic leukemia To the Editor: We read with interest the recent report by Magro and colleagues1 highlighting the pathologic findings in cutaneous presentations of T-cell prolymphocytic leukemia (T-PLL). T-PLL is a rare aggressive neoplasm of T-lymphocytes, with usually a mature immunophenotype and characterized by prominent lymphocytosis and systemic multiorgan involvement.2,3 Although extramedullary manifestations are common, with skin being one of the most frequently involved sites,2-4 descriptions of the pathologic findings of T-PLL involving extramedullary sites are limited because the diagnosis and follow up rely heavily on peripheral blood and bone marrow analysis. In their article, Magro et al document 6 cases of T-PLL with skin involvement. Given the low overall frequency of T-PLL,5 we thought that it might be of interest to communicate our experience with skin biopsy specimens involved by T-PLL. From a group of 41 patients with T-PLL, we previously described the pathologic findings in 7 patients (17%) with skin involvement who underwent biopsy.5 Although clinically prominent skin manifestations were frequent (14/41; 34%), findings similar to those other series,5 histologic documentation of cutaneous involvement, either at the time of initial diagnosis or during disease progression, is much less common. Clinically, skin involvement in our series was diverse and included edema, rashes, and macular/papular lesions involving face or other areas. We also noted a wide cytomorphological spectrum of T-PLL in skin, ranging from classic nucleolated prolymphocytes, to medium-sized cells with regular nuclei and inconspicuous nucleoli, to small cells with cerebriform or Se´zary cellelike nuclear contours. The atypical infiltrate had perivascular and/or periadnexal accentuation, similar to the pattern reported by Magro et al.1 Of note, in our series one patient developed a subcutaneous mass, and in two skin biopsy specimens epidermotropism was observed. An updated analysis of our current clinicopathologic data on 43 patients with T-PLL according to clinical evidence of skin involvement reveals no significant difference in overall survival (34.3 vs 27.4 months, with vs without involvement, respectively;
534 Letters
J AM ACAD DERMATOL SEPTEMBER 2007
P = .78, log-rank test) or other clinical features. Among 34 patients with available data, the group of patients with skin lesions at the time of presentation showed significantly higher levels of tumor cell p65 nuclear factor kB expression (2-tier scoring by immunohistochemistry, P = .023, x2 test; confirmatory Western blot in 14/34 patients), a feature often found in association with T-cell activation or lymphoma progression. We conclude that skin involved by T-PLL, although common, is subjected to biopsy infrequently and reflects the aggressive disease course but likely does not represent a feature useful for distinguishing prognostic subsets. In addition, our analysis indicates that skin involvement in T-PLL is associated with a more diverse clinical and morphological spectrum than suggested by Magro et al.1 In our experience, immunohistochemical staining for TCL1 is a useful diagnostic aid in discriminating T-PLL from other T-cell tumors.3,5,6 However, a subset of T-PLL cases does not express TCL1. Interestingly, we observed a slightly higher number of cases with skin infiltration in these patients with TCL1negative tumors.3 Overall, T-PLL represents a heterogeneous entity both biologically and clinically as it also shows considerable clinicopathologic overlap with other T-cell tumors that involve peripheral blood and/or skin, such as Se´zary syndrome.3 Given the diagnostic difficulties and therapeutic challenges in T-PLL,7 refined systematic analyses are needed. Marco Herling, MD,a,b Jose R. Valbuena, MD,a,c Dan Jones, MD, PhD,a and L. Jeffrey Medeiros, MDa Department of Hematopathology, The University of Texas, M. D. Anderson Cancer Center, Houston,a the Department of Hematology/Medical Oncology, Cologne University, Germany,b and Anatomic Pathology, Pontificia Universidad Catolica de Chilec Supported by a DFG young investigator grant (HE3553/2-1) to M.H. Conflicts of interest: None declared. Correspondence to: Marco Herling, MD, Hematology/Medical Oncology, University of Cologne, Kerpenerstrasse 62, LFI, Level 4, Room 058a, Cologne 50931, Germany E-mail: [email protected] REFERENCES 1. Magro CM, Morrison CD, Heerema N, Porcu P, Sroa N, Deng AC. T-cell prolymphocytic leukemia: an aggressive T cell malignancy
2.
3.
4.
5.
6.
7.
with frequent cutaneous tropism. J Am Acad Dermatol 2006; 55:467-77. Matutes E, Brito-Babapulle V, Swansbury J, Ellis J, Morilla R, Dearden C, et al. Clinical and laboratory features of 78 cases of T-prolymphocytic leukemia. Blood 1991;78:3269-74. Herling M, Khoury JD, Washington LT, Duvic M, Keating MJ, Jones D. A systematic approach to diagnosis of mature T-cell leukemias reveals heterogeneity among WHO categories. Blood 2004;15:328-35. Mallett RB, Matutes E, Catovsky D, Maclennan K, Mortimer PS, Holden CA. Cutaneous infiltration in T-cell prolymphocytic leukemia. Br J Dermatol 1995;132:263-6. Valbuena JR, Herling M, Admirand JH, Padula A, Jones D, Medeiros LJ. T-cell prolymphocytic leukemia involving extramedullary sites. Am J Clin Pathol 2005;123:456-64. Herling M, Teitell MA, Shen RR, Medeiros LJ, Jones D. TCL1 expression in plasmacytoid dendritic cells (DC2) and the related CD41 CD561 blastic tumors of skin. Blood 2003;101:5007-9. Ravandi F, O’Brien S, Jones D, Lerner S, Faderl S, Ferrajoli A, et al. T-cell prolymphocytic leukemia (T-PLL): a single institution experience. Clin Lymphoma Myeloma 2005;6:234-9. doi:10.1016/j.jaad.2007.02.034
Case of multiple verrucous carcinomas responding to treatment with acetretin more likely to have been a case of verrucous psoriasis To the Editor: In the February 2007 case reports supplement, Kuan et al1 described a case of multiple verrucous carcinomas that responded to treatment with acetretin. Both the clinical and histologic findings, however, cause us to question the diagnosis and wonder whether this may well be a case of psoriasis. Multiple verrucous carcinomas occurring in the same patient, as acknowledged by the authors, are rare. The clinical description and accompanying images of hyperkeratotic plaques over both feet, ankles and the left thigh persisting for 3 years is very atypical. Verrucous carcinoma on the feet typically appears as warty, well-circumscribed lesions with a cauliflower-like appearance that are often mistaken for verrucae and have a predilection for the weightbearing areas of the soles.2 The histologic diagnosis of verrucous carcinoma is difficult. The authors stated that 6 biopsy specimens were obtained from different sites and that ‘‘. . . all specimens showed marked parakeratosis, neoplastic proliferation, and downward invasion of epidermal keratinocytes with a blunt border and a pushed down, bulldozing appearance.’’ Verrucous carcinoma is histologically characterized by blunt papillary projections of well-differentiated epithelium, with tumor islands in the thickened papillary dermis supported by edematous, nonreactive stroma. The image of the biopsy specimen supplied only visualized the epidermis and minimal dermis
Letters 533
VOLUME 57, NUMBER 3
therapy (HT) and estrogen therapy (ET).2 The North American Menopause Society recommends using HT as a general term encompassing the more specific terms ET for estrogen therapy and EPT for estrogen/ progestin therapy.3 As our knowledge becomes more sophisticated, other subtleties in terminology emerge. Historically, various synthetic or equine estradiol analogs (estrogens) were considered functionally identical to estradiol and to each other and the terms were often used interchangeably. Both the Food and Drug Administration and North American Menopause Society still state that until reliable evidence proves otherwise, we must assume that the risks and benefits of all estrogens are the same.2,3 However, accumulating evidence makes it clear that conjugated equine estrogens (Premarin) and synthetic analogs (ethinyl estradiol, esterified estrogens) differ from the predominant human hormone, estradiol, and from each other.4,5 Effects vary in different tissues, presumably because of the variable receptor affinity for slightly different molecules. Hall and Phillips attempted valiantly to differentiate among the estrogens, employing the different terms used in the various references they reviewed. Unfortunately, research in this area has progressed with great confusion of terms, measurements, baselines, doses, delivery systems, and regimens. We should not be surprised to find conflicting results and conclusions. When we review the literature of female hormone science, our challenge is not only to identify estrogen’s effects, but to understand how the effects differ with the different estrogen analogs. Valori Treloar, MD Integrative Dermatology, PC Funding sources: None. Conflicts of interest: None declared. Correspondence to: Valori Treloar, MD, Integrative Dermatology, PC, 1172 Beacon St, Suite 402, Newton, MA 02461 REFERENCES 1. Hall G, Phillips TJ. Estrogen and skin: the effects of estrogen, menopause, and hormone replacement therapy on the skin. J Am Acad Dermatol 2005;53:555-68. 2. FDA Docket No. 03D-0007. Draft guidance for industry on estrogen and estrogen/progestin drug products to treat vasomotor symptoms and vulvar and vaginal atrophy symptomse Recommendations for clinical evaluation; availability. Margaret M. Dotzel, Assistance Commissioner for Policy, Health and Human Services. January 23, 2003. 3. Menopause practice: a clinician’s guide. Cleveland (OH): The North American Menopause Society; 2004. p. 113.
4. Smith NL, Heckbert SR, Lemaitre RN, Reiner AP, Lumley T, Weiss NS, et al. Esterified estrogens and conjugated equine estrogens and the risk of venous thrombosis. JAMA 2004;292:1581-7. 5. Leng XH, Zhang W, Nieswandt B, Bray PF. Effects of estrogen replacement therapies on mouse platelet function and glycoprotein VI levels. Circ Res 2005;97:415-7. doi:10.1016/j.jaad.2006.02.048
Skin involvement in T-cell prolymphocytic leukemia To the Editor: We read with interest the recent report by Magro and colleagues1 highlighting the pathologic findings in cutaneous presentations of T-cell prolymphocytic leukemia (T-PLL). T-PLL is a rare aggressive neoplasm of T-lymphocytes, with usually a mature immunophenotype and characterized by prominent lymphocytosis and systemic multiorgan involvement.2,3 Although extramedullary manifestations are common, with skin being one of the most frequently involved sites,2-4 descriptions of the pathologic findings of T-PLL involving extramedullary sites are limited because the diagnosis and follow up rely heavily on peripheral blood and bone marrow analysis. In their article, Magro et al document 6 cases of T-PLL with skin involvement. Given the low overall frequency of T-PLL,5 we thought that it might be of interest to communicate our experience with skin biopsy specimens involved by T-PLL. From a group of 41 patients with T-PLL, we previously described the pathologic findings in 7 patients (17%) with skin involvement who underwent biopsy.5 Although clinically prominent skin manifestations were frequent (14/41; 34%), findings similar to those other series,5 histologic documentation of cutaneous involvement, either at the time of initial diagnosis or during disease progression, is much less common. Clinically, skin involvement in our series was diverse and included edema, rashes, and macular/papular lesions involving face or other areas. We also noted a wide cytomorphological spectrum of T-PLL in skin, ranging from classic nucleolated prolymphocytes, to medium-sized cells with regular nuclei and inconspicuous nucleoli, to small cells with cerebriform or Se´zary cellelike nuclear contours. The atypical infiltrate had perivascular and/or periadnexal accentuation, similar to the pattern reported by Magro et al.1 Of note, in our series one patient developed a subcutaneous mass, and in two skin biopsy specimens epidermotropism was observed. An updated analysis of our current clinicopathologic data on 43 patients with T-PLL according to clinical evidence of skin involvement reveals no significant difference in overall survival (34.3 vs 27.4 months, with vs without involvement, respectively;
534 Letters
J AM ACAD DERMATOL SEPTEMBER 2007
P = .78, log-rank test) or other clinical features. Among 34 patients with available data, the group of patients with skin lesions at the time of presentation showed significantly higher levels of tumor cell p65 nuclear factor kB expression (2-tier scoring by immunohistochemistry, P = .023, x2 test; confirmatory Western blot in 14/34 patients), a feature often found in association with T-cell activation or lymphoma progression. We conclude that skin involved by T-PLL, although common, is subjected to biopsy infrequently and reflects the aggressive disease course but likely does not represent a feature useful for distinguishing prognostic subsets. In addition, our analysis indicates that skin involvement in T-PLL is associated with a more diverse clinical and morphological spectrum than suggested by Magro et al.1 In our experience, immunohistochemical staining for TCL1 is a useful diagnostic aid in discriminating T-PLL from other T-cell tumors.3,5,6 However, a subset of T-PLL cases does not express TCL1. Interestingly, we observed a slightly higher number of cases with skin infiltration in these patients with TCL1negative tumors.3 Overall, T-PLL represents a heterogeneous entity both biologically and clinically as it also shows considerable clinicopathologic overlap with other T-cell tumors that involve peripheral blood and/or skin, such as Se´zary syndrome.3 Given the diagnostic difficulties and therapeutic challenges in T-PLL,7 refined systematic analyses are needed. Marco Herling, MD,a,b Jose R. Valbuena, MD,a,c Dan Jones, MD, PhD,a and L. Jeffrey Medeiros, MDa Department of Hematopathology, The University of Texas, M. D. Anderson Cancer Center, Houston,a the Department of Hematology/Medical Oncology, Cologne University, Germany,b and Anatomic Pathology, Pontificia Universidad Catolica de Chilec Supported by a DFG young investigator grant (HE3553/2-1) to M.H. Conflicts of interest: None declared. Correspondence to: Marco Herling, MD, Hematology/Medical Oncology, University of Cologne, Kerpenerstrasse 62, LFI, Level 4, Room 058a, Cologne 50931, Germany E-mail: [email protected] REFERENCES 1. Magro CM, Morrison CD, Heerema N, Porcu P, Sroa N, Deng AC. T-cell prolymphocytic leukemia: an aggressive T cell malignancy
2.
3.
4.
5.
6.
7.
with frequent cutaneous tropism. J Am Acad Dermatol 2006; 55:467-77. Matutes E, Brito-Babapulle V, Swansbury J, Ellis J, Morilla R, Dearden C, et al. Clinical and laboratory features of 78 cases of T-prolymphocytic leukemia. Blood 1991;78:3269-74. Herling M, Khoury JD, Washington LT, Duvic M, Keating MJ, Jones D. A systematic approach to diagnosis of mature T-cell leukemias reveals heterogeneity among WHO categories. Blood 2004;15:328-35. Mallett RB, Matutes E, Catovsky D, Maclennan K, Mortimer PS, Holden CA. Cutaneous infiltration in T-cell prolymphocytic leukemia. Br J Dermatol 1995;132:263-6. Valbuena JR, Herling M, Admirand JH, Padula A, Jones D, Medeiros LJ. T-cell prolymphocytic leukemia involving extramedullary sites. Am J Clin Pathol 2005;123:456-64. Herling M, Teitell MA, Shen RR, Medeiros LJ, Jones D. TCL1 expression in plasmacytoid dendritic cells (DC2) and the related CD41 CD561 blastic tumors of skin. Blood 2003;101:5007-9. Ravandi F, O’Brien S, Jones D, Lerner S, Faderl S, Ferrajoli A, et al. T-cell prolymphocytic leukemia (T-PLL): a single institution experience. Clin Lymphoma Myeloma 2005;6:234-9. doi:10.1016/j.jaad.2007.02.034
Case of multiple verrucous carcinomas responding to treatment with acetretin more likely to have been a case of verrucous psoriasis To the Editor: In the February 2007 case reports supplement, Kuan et al1 described a case of multiple verrucous carcinomas that responded to treatment with acetretin. Both the clinical and histologic findings, however, cause us to question the diagnosis and wonder whether this may well be a case of psoriasis. Multiple verrucous carcinomas occurring in the same patient, as acknowledged by the authors, are rare. The clinical description and accompanying images of hyperkeratotic plaques over both feet, ankles and the left thigh persisting for 3 years is very atypical. Verrucous carcinoma on the feet typically appears as warty, well-circumscribed lesions with a cauliflower-like appearance that are often mistaken for verrucae and have a predilection for the weightbearing areas of the soles.2 The histologic diagnosis of verrucous carcinoma is difficult. The authors stated that 6 biopsy specimens were obtained from different sites and that ‘‘. . . all specimens showed marked parakeratosis, neoplastic proliferation, and downward invasion of epidermal keratinocytes with a blunt border and a pushed down, bulldozing appearance.’’ Verrucous carcinoma is histologically characterized by blunt papillary projections of well-differentiated epithelium, with tumor islands in the thickened papillary dermis supported by edematous, nonreactive stroma. The image of the biopsy specimen supplied only visualized the epidermis and minimal dermis