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Patchy alopecia following chemotherapy
536 JAAD grand rounds
J AM ACAD DERMATOL MARCH 2010
inflammation, such as an elevated erythrocyte sedimentation rate, elevated levels of C-reactive protein, thrombocytosis, and mild normocytic or microcytic anemia. The treatment of DCS is varied and consists of both medical and surgical options. The disease is often recalcitrant to medical therapies. Agents reported to control the inflammatory process in some patients with DCS include: topical and oral isotretinoin, intralesional corticosteroids, antibiotic soaps (chlorohexidine and benzoyl peroxide), dapsone, infliximab, adalimumab, zinc supplements, oral antibiotics, and oral corticosteroids. Combination therapy, for example with oral antiinflammatory antibiotics (eg, tetracyclines) and intralesional corticosteroids is often more successful than monotherapy, and may be combined with other systemic and topical agents. Procedural treatments, such as incision and drainage with marsupialization of intercommunicating sinuses, ablative and epilating laser treatments, grafting, and total scalp excision followed by skin grafting and epilating radiation therapy are approaches that may be employed when medical therapy fails; however, aggressive procedural modalities typically lead to permanent alopecia and some degree of scarring. The prognosis for complete recovery from DCS is poor. For this series, the recommended choices are: 1, c; 2, d; 3, d; 4, a; 5, e; and 6, a. BIBLIOGRAPHY Chinnaiyan P, Tena LB, Brenner MJ, Welsh JS. Modern external beam radiation therapy for refractory dissecting cellulitis of the scalp. Br J Dermatol 2005;152:777-9. Chui CT, Berger TG, Price VH, Zachary CB. Recalcitrant scarring follicular disorders treated by laser-assisted hair removal: a preliminary report. Dermatol Surg 1999;25:34-7. James WD, Berger TG, Elston DM. Acne. In: James WD, Berger TG, Elston DM, editors. Andrews’ diseases of the skin: clinical dermatology. 10th ed. Philadelphia: Saunders Elsevier, Inc; 2006. pp. 760-1. Salim A, David J, Holder J. Dissecting cellulitis of the scalp with associated spondylarthropathy: case report and review. J Eur Acad Dermatol Venereol 2003;17:689-91. Scheinfeld NS. A case of dissecting cellulitis and a review of the literature. Dermatol Online J 2003;9:8. Sukhatme AV, Lenzy YM, Gottlieb AB. Refractory dissecting cellulitis of the scalp treated with adalimumab. J Drugs Dermatol 2008;7:981-3.
Patchy alopecia following chemotherapy Joslyn S. Kirby, MD,a Mahsa Tehrani, MS,b and Michael D. Ioffreda, MDa Hershey, Pennsylvania,a and Washington, DCb A 57-year-old white female presented with small, scattered patches of alopecia. She had a history of
metastatic ductal breast cancer, and 2 months before her visit had finished three cycles of adriamycin and cyclophosphamide followed by three cycles of docetaxol and cyclophosphamide. Her current medications included anastrazole and omeprazole. She denied any areas of alopecia before treatment, and she lost all of her hair during chemotherapy. Following chemotherapy, she noticed that some areas of her scalp remained bald. She denied pruritus, pain, and flaking. She had not attempted to treat the condition. She denied any personal or family history of autoimmune disorders. Her review of systems was negative. A physical examination revealed many scattered, 1- to 2-cm, white, atrophic patches of alopecia (Fig 2). A biopsy specimen was taken and anticytokeratin (CAM 5.2) staining was performed (Figs 3 and 4). 7. What is the most likely diagnosis? a. Pseudopelade of Brocq b. Alopecia neoplastica c. Trichotillosis d. Basal cell carcinoma, infiltrative type e. Morphea 8. Which of these conditions can clinically mimic this disease? a. Alopecia areata b. Discoid lupus erythematosus c. Lichen planopilaris d. Alopecia mucinosa e. All of the above 9. What is the most common malignancy associated with this disease? a. Lung carcinoma b. Ovarian carcinoma c. Gastric adenocarcinoma d. Breast adenocarcinoma e. Prostate adenocarcinoma 10. Which of the following may cause destruction of the follicle? a. Infiltration of the follicular sheath by neoplastic cells b. Fibroplasia of the dermis c. Effects by cytokines, such as interleukin-4, fibroblast growth factor, and transforming growth factor-beta d. Mass effect by the malignant cells e. All of the above 11. Which of the following statements is true? a. Cutaneous metastasis, including alopecia neoplastica, does not impact prognosis. b. Hair loss is always permanent. c. Cutaneous metastases most often precede diagnosis of malignancy.
J AM ACAD DERMATOL
JAAD grand rounds 537
VOLUME 62, NUMBER 3
d. Treatment of the hair loss is primarily treatment of the underlying malignancy. e. Cutaneous metastases occur in about 12% of cancer patients. Discussion Cutaneous metastases from an underlying malignancy are uncommon, and alopecia neoplastica (AN) is a rare form of cutaneous metastasis. AN is most commonly defined as alopecia caused by the cutaneous infiltration of malignant cells from a distant malignancy. A metaanalysis estimated the prevalence of cutaneous metastasis to be about 5%, while individual estimates range from 0.7% to 9%. AN can have a variable clinical appearance. It can present as single or multiple alopecic patches, plaques, or nodules, and has been reported to mimic alopecia areata, discoid lupus, and pseudopelade of Brocq. The differential diagnosis also includes tinea capitis, lichen planopilaris, and alopecia mucinosa. AN is most commonly associated with breast cancer.
It has also been associated with cervical cancer, gastric and colonic adenocarcinoma, melanoma, lymphoma, extramammary Paget disease, and other conditions. A scalp biopsy specimen often reveals relatively sparse neoplastic cells in a highly collagenous stroma and partial to complete disappearance of the pilosebaceous units. The pathophysiology of the destruction of the pilosebaceous unit is not understood. It may be caused by fibroplasia induced by the neoplastic cells. Histologic evaluation of our patient revealed the partial to complete absence of hair follicles, follicular scars, absence of sebaceous glands, and the presence of strands of single-file (‘‘Indian-filing’’) basophilic cuboidal cells (Fig 3). There was infiltration of these cells into the follicular tracts, and the cells demonstrated signet ring forms and intracytoplasmic vacuoles. In addition, the abnormal cells stained positively with CAM 5.2 (Fig 4), which is an immunostain for low molecular weight keratins. These findings are consistent with AN caused by metastatic breast cancer. CAM 5.2 stain reacts with secretory epithelia, neuroendocrine tumors, and some sarcomas, such as renal cell carcinoma, extramammary and mammary Paget disease, Merkel cell carcinoma, and epithelioid sarcoma, but not normal stratified squamous epithelium or melanoma. The pathophysiology of AN is not definitively understood. Theories include destruction by direct infiltration by of the hair sheath by the neoplastic cells, fibroplasias caused by or in response to the neoplastic cells, and injury by cytokines, such as interleukin-4, transforming growth factor-beta, and fibroblast growth factor. Treatment is aimed at the underlying malignancy. Archer and Smith reported a patient with AN caused by breast cancer that regrew some hair during treatment with tamoxifen. Cutaneous metastases and AN often portend a poor prognosis and occur in patients with a known malignancy. There are rare instances of AN leading to the diagnosis of the
538 JAAD grand rounds
J AM ACAD DERMATOL MARCH 2010
underlying malignancy. However, scalp metastases typically develop years after the primary malignancy is diagnosed. The case discussed here continues to be closely followed by an oncologist. Her metastatic disease is stable. For this series, the recommended choices are: 7, b; 8, e; 9, d; 10, e; and 11, d. BIBLIOGRAPHY Archer CB, Smith NP. Alopecia neoplastica responsive to tamoxifen. J R Soc Med 1990;83:647-8. Baran R. Alopecic metastases secondary to mammary cancer. Sclerous form (pseudopeladic state) [in French]. Bull Soc Fr Dermatol Syphiligr 1965;72:154-5. Carson HJ, Pellettiere EV, Lack E. Alopecia neoplastica simulating alopecia areata and antedating the detection of primary breast carcinoma. J Cutan Pathol 1994;21:67-70. Cohen I, Levy E, Schreiber H. alopecia neoplastica due to breast carcinoma. Arch Dermatol 1961;84:490-2. Connor KB, Cohen PR. Cutaneous metastasis of breast carcinoma presenting as alopecia neoplastica. South Med J 2009;102: 385-9. Kaplan RP. Specific cutaneous manifestations of internal malignancy. Adv Dermatol 1986;1:3-42. Krathen RA, Orengo IF, Rosen T. Cutaneous metastasis: a metaanalysis of data. South Med J 2003;96:164-7. Leong ASY, Cooper K, Leong FJWM, editors. Manual of diagnostic antibodies for immunohistology. 2nd ed. London: Greenwich Medical Media; 2003. Lin WL, Lin WC, Jung SM, Yang CH, Hong HS. Breast cancer metastasized to the scalp mimicking alopecia areata: alopecia neoplastica. Breast J 2007;13:94-5. Scheinfeld N. Review of scalp alopecia due to a clinically unapparent or minimally apparent neoplasm (SACUMAN). Acta Derm Venereol 2006;86:387-92.
Linear scalp plaques Mario L. Pinoli, MS,a Nathan W. Hanson, MD,b Michael J. Wells, MD,b and Cloyce L. Stetson, MDb El Pasoa and Lubbock,b Texas An 88-year-old white man presented to our department for the evaluation of multiple scalp lesions of relatively recent onset. There was no pertinent family history. He denied trauma to the area, ever having been diagnosed with an infection of the area caused by herpes simplex virus (HSV) or varicella zoster virus (VZV), and ever having received radiation therapy. The physical examination revealed multiple indurated, red, and slightly violaceous plaques and nodules on the scalp in a strikingly linear pattern. The collection of tumors covered a 9 cm 3 3 cm area on the right forehead, frontal scalp, and parietal scalp (Fig 5). There was no clinical lymphadenopathy. Review by a dermatopathologist yielded a diagnosis of malignant epithelioid neoplasm, and additional special stains
were performed. Immunohistochemical staining showed strong staining with CD31 and vimentin and negative staining with CD68, S-100 protein, HMB45, CK7, CK20, CD43, pancytokeratin, CK5/6, CD20, CD34, chromogranin, synaptophysin, mucicarmine, and carcinoembryonic antigen stains. 12. Based on the patient’s presentation and pathologic results, what is the next step? a. Karyotype biopsy specimen b. Referral to the departments of surgery and radiation oncology c. Positron emission tomography scan of the chest d. Computed tomography scan of the abdomen e. Bone marrow biopsy 13. What is the most likely diagnosis? a. Metastatic melanoma b. Spindle cell neoplasm with neuroendocrine differentiation c. Clear cell sarcoma d. Angiosarcoma e. Malignant peripheral nerve sheath tumor 14. Which of the following has NOT been an associated contributing factor to this diagnosis? a. Secondary VZV infection b. Long-standing lymphedema c. Actinic keratoses d. Irradiation e. Trauma 15. Which of the following cell types do NOT stain positively with CD31? a. Melanocytes b. Platelets c. Embryonic stem cells d. Endothelial cells e. Neutrophils The diagnosis was angiosarcoma. The patient was referred to the departments of surgery and radiation oncology. The treatment team decided he was a poor surgical candidate because of his coexisting medical
J AM ACAD DERMATOL MARCH 2010
inflammation, such as an elevated erythrocyte sedimentation rate, elevated levels of C-reactive protein, thrombocytosis, and mild normocytic or microcytic anemia. The treatment of DCS is varied and consists of both medical and surgical options. The disease is often recalcitrant to medical therapies. Agents reported to control the inflammatory process in some patients with DCS include: topical and oral isotretinoin, intralesional corticosteroids, antibiotic soaps (chlorohexidine and benzoyl peroxide), dapsone, infliximab, adalimumab, zinc supplements, oral antibiotics, and oral corticosteroids. Combination therapy, for example with oral antiinflammatory antibiotics (eg, tetracyclines) and intralesional corticosteroids is often more successful than monotherapy, and may be combined with other systemic and topical agents. Procedural treatments, such as incision and drainage with marsupialization of intercommunicating sinuses, ablative and epilating laser treatments, grafting, and total scalp excision followed by skin grafting and epilating radiation therapy are approaches that may be employed when medical therapy fails; however, aggressive procedural modalities typically lead to permanent alopecia and some degree of scarring. The prognosis for complete recovery from DCS is poor. For this series, the recommended choices are: 1, c; 2, d; 3, d; 4, a; 5, e; and 6, a. BIBLIOGRAPHY Chinnaiyan P, Tena LB, Brenner MJ, Welsh JS. Modern external beam radiation therapy for refractory dissecting cellulitis of the scalp. Br J Dermatol 2005;152:777-9. Chui CT, Berger TG, Price VH, Zachary CB. Recalcitrant scarring follicular disorders treated by laser-assisted hair removal: a preliminary report. Dermatol Surg 1999;25:34-7. James WD, Berger TG, Elston DM. Acne. In: James WD, Berger TG, Elston DM, editors. Andrews’ diseases of the skin: clinical dermatology. 10th ed. Philadelphia: Saunders Elsevier, Inc; 2006. pp. 760-1. Salim A, David J, Holder J. Dissecting cellulitis of the scalp with associated spondylarthropathy: case report and review. J Eur Acad Dermatol Venereol 2003;17:689-91. Scheinfeld NS. A case of dissecting cellulitis and a review of the literature. Dermatol Online J 2003;9:8. Sukhatme AV, Lenzy YM, Gottlieb AB. Refractory dissecting cellulitis of the scalp treated with adalimumab. J Drugs Dermatol 2008;7:981-3.
Patchy alopecia following chemotherapy Joslyn S. Kirby, MD,a Mahsa Tehrani, MS,b and Michael D. Ioffreda, MDa Hershey, Pennsylvania,a and Washington, DCb A 57-year-old white female presented with small, scattered patches of alopecia. She had a history of
metastatic ductal breast cancer, and 2 months before her visit had finished three cycles of adriamycin and cyclophosphamide followed by three cycles of docetaxol and cyclophosphamide. Her current medications included anastrazole and omeprazole. She denied any areas of alopecia before treatment, and she lost all of her hair during chemotherapy. Following chemotherapy, she noticed that some areas of her scalp remained bald. She denied pruritus, pain, and flaking. She had not attempted to treat the condition. She denied any personal or family history of autoimmune disorders. Her review of systems was negative. A physical examination revealed many scattered, 1- to 2-cm, white, atrophic patches of alopecia (Fig 2). A biopsy specimen was taken and anticytokeratin (CAM 5.2) staining was performed (Figs 3 and 4). 7. What is the most likely diagnosis? a. Pseudopelade of Brocq b. Alopecia neoplastica c. Trichotillosis d. Basal cell carcinoma, infiltrative type e. Morphea 8. Which of these conditions can clinically mimic this disease? a. Alopecia areata b. Discoid lupus erythematosus c. Lichen planopilaris d. Alopecia mucinosa e. All of the above 9. What is the most common malignancy associated with this disease? a. Lung carcinoma b. Ovarian carcinoma c. Gastric adenocarcinoma d. Breast adenocarcinoma e. Prostate adenocarcinoma 10. Which of the following may cause destruction of the follicle? a. Infiltration of the follicular sheath by neoplastic cells b. Fibroplasia of the dermis c. Effects by cytokines, such as interleukin-4, fibroblast growth factor, and transforming growth factor-beta d. Mass effect by the malignant cells e. All of the above 11. Which of the following statements is true? a. Cutaneous metastasis, including alopecia neoplastica, does not impact prognosis. b. Hair loss is always permanent. c. Cutaneous metastases most often precede diagnosis of malignancy.
J AM ACAD DERMATOL
JAAD grand rounds 537
VOLUME 62, NUMBER 3
d. Treatment of the hair loss is primarily treatment of the underlying malignancy. e. Cutaneous metastases occur in about 12% of cancer patients. Discussion Cutaneous metastases from an underlying malignancy are uncommon, and alopecia neoplastica (AN) is a rare form of cutaneous metastasis. AN is most commonly defined as alopecia caused by the cutaneous infiltration of malignant cells from a distant malignancy. A metaanalysis estimated the prevalence of cutaneous metastasis to be about 5%, while individual estimates range from 0.7% to 9%. AN can have a variable clinical appearance. It can present as single or multiple alopecic patches, plaques, or nodules, and has been reported to mimic alopecia areata, discoid lupus, and pseudopelade of Brocq. The differential diagnosis also includes tinea capitis, lichen planopilaris, and alopecia mucinosa. AN is most commonly associated with breast cancer.
It has also been associated with cervical cancer, gastric and colonic adenocarcinoma, melanoma, lymphoma, extramammary Paget disease, and other conditions. A scalp biopsy specimen often reveals relatively sparse neoplastic cells in a highly collagenous stroma and partial to complete disappearance of the pilosebaceous units. The pathophysiology of the destruction of the pilosebaceous unit is not understood. It may be caused by fibroplasia induced by the neoplastic cells. Histologic evaluation of our patient revealed the partial to complete absence of hair follicles, follicular scars, absence of sebaceous glands, and the presence of strands of single-file (‘‘Indian-filing’’) basophilic cuboidal cells (Fig 3). There was infiltration of these cells into the follicular tracts, and the cells demonstrated signet ring forms and intracytoplasmic vacuoles. In addition, the abnormal cells stained positively with CAM 5.2 (Fig 4), which is an immunostain for low molecular weight keratins. These findings are consistent with AN caused by metastatic breast cancer. CAM 5.2 stain reacts with secretory epithelia, neuroendocrine tumors, and some sarcomas, such as renal cell carcinoma, extramammary and mammary Paget disease, Merkel cell carcinoma, and epithelioid sarcoma, but not normal stratified squamous epithelium or melanoma. The pathophysiology of AN is not definitively understood. Theories include destruction by direct infiltration by of the hair sheath by the neoplastic cells, fibroplasias caused by or in response to the neoplastic cells, and injury by cytokines, such as interleukin-4, transforming growth factor-beta, and fibroblast growth factor. Treatment is aimed at the underlying malignancy. Archer and Smith reported a patient with AN caused by breast cancer that regrew some hair during treatment with tamoxifen. Cutaneous metastases and AN often portend a poor prognosis and occur in patients with a known malignancy. There are rare instances of AN leading to the diagnosis of the
538 JAAD grand rounds
J AM ACAD DERMATOL MARCH 2010
underlying malignancy. However, scalp metastases typically develop years after the primary malignancy is diagnosed. The case discussed here continues to be closely followed by an oncologist. Her metastatic disease is stable. For this series, the recommended choices are: 7, b; 8, e; 9, d; 10, e; and 11, d. BIBLIOGRAPHY Archer CB, Smith NP. Alopecia neoplastica responsive to tamoxifen. J R Soc Med 1990;83:647-8. Baran R. Alopecic metastases secondary to mammary cancer. Sclerous form (pseudopeladic state) [in French]. Bull Soc Fr Dermatol Syphiligr 1965;72:154-5. Carson HJ, Pellettiere EV, Lack E. Alopecia neoplastica simulating alopecia areata and antedating the detection of primary breast carcinoma. J Cutan Pathol 1994;21:67-70. Cohen I, Levy E, Schreiber H. alopecia neoplastica due to breast carcinoma. Arch Dermatol 1961;84:490-2. Connor KB, Cohen PR. Cutaneous metastasis of breast carcinoma presenting as alopecia neoplastica. South Med J 2009;102: 385-9. Kaplan RP. Specific cutaneous manifestations of internal malignancy. Adv Dermatol 1986;1:3-42. Krathen RA, Orengo IF, Rosen T. Cutaneous metastasis: a metaanalysis of data. South Med J 2003;96:164-7. Leong ASY, Cooper K, Leong FJWM, editors. Manual of diagnostic antibodies for immunohistology. 2nd ed. London: Greenwich Medical Media; 2003. Lin WL, Lin WC, Jung SM, Yang CH, Hong HS. Breast cancer metastasized to the scalp mimicking alopecia areata: alopecia neoplastica. Breast J 2007;13:94-5. Scheinfeld N. Review of scalp alopecia due to a clinically unapparent or minimally apparent neoplasm (SACUMAN). Acta Derm Venereol 2006;86:387-92.
Linear scalp plaques Mario L. Pinoli, MS,a Nathan W. Hanson, MD,b Michael J. Wells, MD,b and Cloyce L. Stetson, MDb El Pasoa and Lubbock,b Texas An 88-year-old white man presented to our department for the evaluation of multiple scalp lesions of relatively recent onset. There was no pertinent family history. He denied trauma to the area, ever having been diagnosed with an infection of the area caused by herpes simplex virus (HSV) or varicella zoster virus (VZV), and ever having received radiation therapy. The physical examination revealed multiple indurated, red, and slightly violaceous plaques and nodules on the scalp in a strikingly linear pattern. The collection of tumors covered a 9 cm 3 3 cm area on the right forehead, frontal scalp, and parietal scalp (Fig 5). There was no clinical lymphadenopathy. Review by a dermatopathologist yielded a diagnosis of malignant epithelioid neoplasm, and additional special stains
were performed. Immunohistochemical staining showed strong staining with CD31 and vimentin and negative staining with CD68, S-100 protein, HMB45, CK7, CK20, CD43, pancytokeratin, CK5/6, CD20, CD34, chromogranin, synaptophysin, mucicarmine, and carcinoembryonic antigen stains. 12. Based on the patient’s presentation and pathologic results, what is the next step? a. Karyotype biopsy specimen b. Referral to the departments of surgery and radiation oncology c. Positron emission tomography scan of the chest d. Computed tomography scan of the abdomen e. Bone marrow biopsy 13. What is the most likely diagnosis? a. Metastatic melanoma b. Spindle cell neoplasm with neuroendocrine differentiation c. Clear cell sarcoma d. Angiosarcoma e. Malignant peripheral nerve sheath tumor 14. Which of the following has NOT been an associated contributing factor to this diagnosis? a. Secondary VZV infection b. Long-standing lymphedema c. Actinic keratoses d. Irradiation e. Trauma 15. Which of the following cell types do NOT stain positively with CD31? a. Melanocytes b. Platelets c. Embryonic stem cells d. Endothelial cells e. Neutrophils The diagnosis was angiosarcoma. The patient was referred to the departments of surgery and radiation oncology. The treatment team decided he was a poor surgical candidate because of his coexisting medical