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JAAD Grand Rounds quiz∗
JAAD
GRAND ROUNDS
A note to our readers: You will notice the JAAD Grand Rounds series appears this month without an opportunity to earn CME credit. Unfortunately, the exhaustive underlying documentation required of journal articles that offer CME credit has become so burdensome that we are forced to abandon this benefit for this popular feature. Rest assured that CME credit is still available for the JAAD lead article. We will continue to strive to provide the best, most clinically relevant articles to assist you in the practice of dermatology.
JAAD Grand Rounds quiz* Milton R. Moore, MD, Kiran Motaparthi, MD, Holly McIntire, MD, Sylvia Hsu, MD, Melissa Mallory, MD, Bridget M. Bryer, MD, Barbara B. Wilson, MD, Nicole Warner, MD, Heather L. Salvaggio, MD, and Andrea L. Zaenglein, MD Instructions: In answering each question, refer to the specific directions provided. Because it is often necessary to provide information occurring later in a series that give away answers to earlier questions, please answer the questions in each series in sequence. ( J Am Acad Dermatol 2013;68:346-52.)
Keloidal nodules in an African American man Milton R. Moore, MD, Kiran Motaparthi, MD, Holly McIntire, MD, and Sylvia Hsu, MD Houston, Texas A 66-year-old African American man presented with a 6-month history of several slow growing, asymptomatic nodules on his trunk. The patient did not complain of constitutional symptoms and his medical history was negative. The physical examination revealed firm, violaceous, indurated nodules, some resembling keloids, on the lower abdomen (Fig 1), right flank, and back. Peripheral lymphadenopathy was absent. The histopathologic examination revealed an inflammatory infiltrate composed of lymphocytes, plasma cells, eosinophils, and vacuolated histiocytes (Figs 2 and 3). Immunohistochemical stains revealed diffuse expression of S-100 by the histiocytes. A complete blood cell count with differential, serum and urine protein electrophoresis, and immunofixation electrophoresis found no abnormalities. 1. What is the most likely diagnosis? a. Sarcoidosis b. Histiocytic lymphoma c. Keloids
The authors, editors, and peer reviewers have no relevant financial relationships. *The Self-Assessment Task Force of the American Academy of Dermatology is led by Erin E. Boh, MD.
346
FEBRUARY 2013
d. RosaieDorfman disease e. Cutaneous B-cell lymphoma 2. This disease is most likely to be associated with which of the following findings? a. Ulceration b. Metastasis c. Lymphadenopathy d. Erythema nodosum e. Cryoglobulinemia 3. What percentage of patients with this condition will present with cutaneous manifestations only? a. 3% b. 7% c. 25% d. 40% e. 75% 4. Primary cutaneous disease occurs most frequently in which of the following patients? a. African Americans b. Children c. Young adults d. Females e. Males 5. Which of the following medications has been reported to be a therapy for this condition? a. Prednisone b. Dapsone c. Isotretinoin d. Thalidomide e. All of the above J AM ACAD DERMATOL
J AM ACAD DERMATOL VOLUME 68, NUMBER 2
Discussion Sinus histiocytosis with massive lymphadenopathy (RosaieDorfman disease [RDD]) is a benign histiocytic proliferative disorder first described by Rosai and Dorfman in 1969. This rare disorder is characterized by massive painless lymphadenopathy, primarily of the cervical lymph nodes. However, any nodal site can be involved. Although this disease primarily affects the lymphatic system, extranodal involvement is fairly common (40%), the skin being the most common extranodal manifestation (11%). RDD is frequently associated with nonspecific laboratory abnormalities, such as mild anemia, elevated erythrocyte sedimentation rate, leukocytosis with neutrophilia, and a polyclonal immunoglobulin G gammopathy. Fever is also frequently reported. A variety of morphologies occur in cutaneous RDD, including erythematous to xanthomatous macules, papules, nodules, or plaques. In African Americans, lesions can present at any site and may resemble keloids. In 1978, Thawerani et al described a primary cutaneous variant of the disease without lymphadenopathy or systemic features. Only 3% of patients with RDD have been reported to manifest isolated cutaneous manifestations. The age distribution of primary cutaneous RDD varies from 15 to 68 years (median, 43.5 years), and a 2:1 female predominance over males has been reported. Primary
JAAD grand rounds 347
cutaneous RDD is more common in whites and Asians, unlike systemic RDD, which is more commonly seen in African Americans. The etiology of RDD remains unknown, but it has been suggested that viruses may play a role. Although EpsteineBarr virus and human herpesvirus 6 have been studied, their role in the pathogenesis of RDD has not been confirmed. Given that the morphology of cutaneous RDD may be nonspecific or variable, diagnosis is dependent on histopathology. Dense dermal infiltrates of histiocytes, lymphocytes, plasma cells, and neutrophils are seen. Emperipolesis, the engulfment of lymphocytes by histiocytes, is a characteristic feature (Fig 4). Classically, histiocytes stain positively for S100 and CD68 and negatively for CD1a. Lesions of cutaneous RDD are asymptomatic and are frequently reported to spontaneously resolve. Supportive care, therefore, is an acceptable treatment modality. However, lesions may cause cosmetic disfigurement or physical impairment. When treatment is indicated, several therapeutic options have been reported with variable efficacy, including excision, systemic steroids, radiation therapy, and isotretinoin. Dapsone and high doses of thalidomide (300 mg/day) have also been reported to be effective for cutaneous lesions. Unfortunately, randomized controlled trials are unavailable because of the rarity of RDD.
348 JAAD grand rounds
J AM ACAD DERMATOL
FEBRUARY 2013
For this series, the recommended choices are: 1, d; 2, c; 3, a; 4, d; 5, e. BIBILIOGRAPHY Bolognia JL, Jorizzo JL, Rapini RP. Dermatology. 2nd ed. Spain: Mosby Elsevier; 2008. Brenn T, Calonje E, Granter SR, Leonard N, Grayson W, Fletcher CD, et al. Cutaneous Rosai-Dorfman disease is a distinct clinical entity. Am J Dermatopathol 2002;24:385-91. Chan CC, Chu CY. Dapsone as a potential treatment for cutaneous Rosai-Dorfman disease with neutrophilic predominance. Arch Dermatol 2006;142:428-30. Kong YY, Kong JC, Shi DR, Lu HF, Zhu XZ, Wang J, et al. Cutaneous Rosai-Dorfman disease: a clinical and histopathologic study of 25 cases in China. Am J Surg Pathol 2007;31:341-50. Levine PH, Jahan N, Murari P, Manak M, Jaffe ES. Detection of human herpesvirus 6 in tissues involved by sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). J Infect Dis 1992;166:291-5. Thawerani H, Sanchez RL, Rosai J, Dorfman RF. The cutaneous manifestations of sinus histiocytosis with massive lymphadenopathy. Arch Dermatol 1978;114:191-7.
Caf e-au-lait macules and enlarging papules on the face Melissa Mallory, MD, Bridget M. Bryer, MD, and Barbara B. Wilson, MD Charlottesville, Virginia A 2-year-old girl was referred by her pediatrician for the evaluation of several lesions on her face and scalp. They were asymptomatic, and the patient’s mother indicated that they were slowly enlarging. She was otherwise healthy with normal development. Her father had a diagnosis of neurofibromatosis. The physical examination revealed a well-appearing girl with several 4- to 5-mm light orange macules on the scalp and 2 small orange-tan papules on the right cheek (Fig 5). She had numerous caf e-au-lait macules scattered on her trunk and 1 soft dermal nodule on the right labia (Fig 6). 6. What is the most likely diagnosis for the lesion depicted in Fig 6? a. Mastocytoma b. Neurofibroma c. Dermoid cyst d. Connective tissue nevus e. Giant molluscum 7. To meet the diagnostic criteria, a patient should have 6 or more caf e-au-lait macules of which of the following sizes? a. 10 mm in prepubertal children; 20 mm in adults b. 5 mm in prepubertal children; 15 mm in adults c. 5 mm in prepubertal children; 10 mm in adults
d. 1 mm in prepubertal children; 5 mm in adults e. 10 mm in prepubertal children; 15 mm in adults 8. Which of the following is not part of the diagnostic criteria for the genodermatosis described in the above case? a. Axillary or inguinal freckling b. Optic glioma c. $ 2 Lisch nodules d. Bilateral acoustic neuromas e. A first-degree relative with neurofibromatosis type I 9. The gene that encodes neurofibromin is found on which chromosome? a. 2 b. 6 c. 9 d. 17 e. 22 10. What is the most common site for extracutaneous involvement in children with multiple lesions like those seen in Fig 5? a. Iris b. Testis c. Kidney d. Spleen e. Central nervous system
GRAND ROUNDS
A note to our readers: You will notice the JAAD Grand Rounds series appears this month without an opportunity to earn CME credit. Unfortunately, the exhaustive underlying documentation required of journal articles that offer CME credit has become so burdensome that we are forced to abandon this benefit for this popular feature. Rest assured that CME credit is still available for the JAAD lead article. We will continue to strive to provide the best, most clinically relevant articles to assist you in the practice of dermatology.
JAAD Grand Rounds quiz* Milton R. Moore, MD, Kiran Motaparthi, MD, Holly McIntire, MD, Sylvia Hsu, MD, Melissa Mallory, MD, Bridget M. Bryer, MD, Barbara B. Wilson, MD, Nicole Warner, MD, Heather L. Salvaggio, MD, and Andrea L. Zaenglein, MD Instructions: In answering each question, refer to the specific directions provided. Because it is often necessary to provide information occurring later in a series that give away answers to earlier questions, please answer the questions in each series in sequence. ( J Am Acad Dermatol 2013;68:346-52.)
Keloidal nodules in an African American man Milton R. Moore, MD, Kiran Motaparthi, MD, Holly McIntire, MD, and Sylvia Hsu, MD Houston, Texas A 66-year-old African American man presented with a 6-month history of several slow growing, asymptomatic nodules on his trunk. The patient did not complain of constitutional symptoms and his medical history was negative. The physical examination revealed firm, violaceous, indurated nodules, some resembling keloids, on the lower abdomen (Fig 1), right flank, and back. Peripheral lymphadenopathy was absent. The histopathologic examination revealed an inflammatory infiltrate composed of lymphocytes, plasma cells, eosinophils, and vacuolated histiocytes (Figs 2 and 3). Immunohistochemical stains revealed diffuse expression of S-100 by the histiocytes. A complete blood cell count with differential, serum and urine protein electrophoresis, and immunofixation electrophoresis found no abnormalities. 1. What is the most likely diagnosis? a. Sarcoidosis b. Histiocytic lymphoma c. Keloids
The authors, editors, and peer reviewers have no relevant financial relationships. *The Self-Assessment Task Force of the American Academy of Dermatology is led by Erin E. Boh, MD.
346
FEBRUARY 2013
d. RosaieDorfman disease e. Cutaneous B-cell lymphoma 2. This disease is most likely to be associated with which of the following findings? a. Ulceration b. Metastasis c. Lymphadenopathy d. Erythema nodosum e. Cryoglobulinemia 3. What percentage of patients with this condition will present with cutaneous manifestations only? a. 3% b. 7% c. 25% d. 40% e. 75% 4. Primary cutaneous disease occurs most frequently in which of the following patients? a. African Americans b. Children c. Young adults d. Females e. Males 5. Which of the following medications has been reported to be a therapy for this condition? a. Prednisone b. Dapsone c. Isotretinoin d. Thalidomide e. All of the above J AM ACAD DERMATOL
J AM ACAD DERMATOL VOLUME 68, NUMBER 2
Discussion Sinus histiocytosis with massive lymphadenopathy (RosaieDorfman disease [RDD]) is a benign histiocytic proliferative disorder first described by Rosai and Dorfman in 1969. This rare disorder is characterized by massive painless lymphadenopathy, primarily of the cervical lymph nodes. However, any nodal site can be involved. Although this disease primarily affects the lymphatic system, extranodal involvement is fairly common (40%), the skin being the most common extranodal manifestation (11%). RDD is frequently associated with nonspecific laboratory abnormalities, such as mild anemia, elevated erythrocyte sedimentation rate, leukocytosis with neutrophilia, and a polyclonal immunoglobulin G gammopathy. Fever is also frequently reported. A variety of morphologies occur in cutaneous RDD, including erythematous to xanthomatous macules, papules, nodules, or plaques. In African Americans, lesions can present at any site and may resemble keloids. In 1978, Thawerani et al described a primary cutaneous variant of the disease without lymphadenopathy or systemic features. Only 3% of patients with RDD have been reported to manifest isolated cutaneous manifestations. The age distribution of primary cutaneous RDD varies from 15 to 68 years (median, 43.5 years), and a 2:1 female predominance over males has been reported. Primary
JAAD grand rounds 347
cutaneous RDD is more common in whites and Asians, unlike systemic RDD, which is more commonly seen in African Americans. The etiology of RDD remains unknown, but it has been suggested that viruses may play a role. Although EpsteineBarr virus and human herpesvirus 6 have been studied, their role in the pathogenesis of RDD has not been confirmed. Given that the morphology of cutaneous RDD may be nonspecific or variable, diagnosis is dependent on histopathology. Dense dermal infiltrates of histiocytes, lymphocytes, plasma cells, and neutrophils are seen. Emperipolesis, the engulfment of lymphocytes by histiocytes, is a characteristic feature (Fig 4). Classically, histiocytes stain positively for S100 and CD68 and negatively for CD1a. Lesions of cutaneous RDD are asymptomatic and are frequently reported to spontaneously resolve. Supportive care, therefore, is an acceptable treatment modality. However, lesions may cause cosmetic disfigurement or physical impairment. When treatment is indicated, several therapeutic options have been reported with variable efficacy, including excision, systemic steroids, radiation therapy, and isotretinoin. Dapsone and high doses of thalidomide (300 mg/day) have also been reported to be effective for cutaneous lesions. Unfortunately, randomized controlled trials are unavailable because of the rarity of RDD.
348 JAAD grand rounds
J AM ACAD DERMATOL
FEBRUARY 2013
For this series, the recommended choices are: 1, d; 2, c; 3, a; 4, d; 5, e. BIBILIOGRAPHY Bolognia JL, Jorizzo JL, Rapini RP. Dermatology. 2nd ed. Spain: Mosby Elsevier; 2008. Brenn T, Calonje E, Granter SR, Leonard N, Grayson W, Fletcher CD, et al. Cutaneous Rosai-Dorfman disease is a distinct clinical entity. Am J Dermatopathol 2002;24:385-91. Chan CC, Chu CY. Dapsone as a potential treatment for cutaneous Rosai-Dorfman disease with neutrophilic predominance. Arch Dermatol 2006;142:428-30. Kong YY, Kong JC, Shi DR, Lu HF, Zhu XZ, Wang J, et al. Cutaneous Rosai-Dorfman disease: a clinical and histopathologic study of 25 cases in China. Am J Surg Pathol 2007;31:341-50. Levine PH, Jahan N, Murari P, Manak M, Jaffe ES. Detection of human herpesvirus 6 in tissues involved by sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). J Infect Dis 1992;166:291-5. Thawerani H, Sanchez RL, Rosai J, Dorfman RF. The cutaneous manifestations of sinus histiocytosis with massive lymphadenopathy. Arch Dermatol 1978;114:191-7.
Caf e-au-lait macules and enlarging papules on the face Melissa Mallory, MD, Bridget M. Bryer, MD, and Barbara B. Wilson, MD Charlottesville, Virginia A 2-year-old girl was referred by her pediatrician for the evaluation of several lesions on her face and scalp. They were asymptomatic, and the patient’s mother indicated that they were slowly enlarging. She was otherwise healthy with normal development. Her father had a diagnosis of neurofibromatosis. The physical examination revealed a well-appearing girl with several 4- to 5-mm light orange macules on the scalp and 2 small orange-tan papules on the right cheek (Fig 5). She had numerous caf e-au-lait macules scattered on her trunk and 1 soft dermal nodule on the right labia (Fig 6). 6. What is the most likely diagnosis for the lesion depicted in Fig 6? a. Mastocytoma b. Neurofibroma c. Dermoid cyst d. Connective tissue nevus e. Giant molluscum 7. To meet the diagnostic criteria, a patient should have 6 or more caf e-au-lait macules of which of the following sizes? a. 10 mm in prepubertal children; 20 mm in adults b. 5 mm in prepubertal children; 15 mm in adults c. 5 mm in prepubertal children; 10 mm in adults
d. 1 mm in prepubertal children; 5 mm in adults e. 10 mm in prepubertal children; 15 mm in adults 8. Which of the following is not part of the diagnostic criteria for the genodermatosis described in the above case? a. Axillary or inguinal freckling b. Optic glioma c. $ 2 Lisch nodules d. Bilateral acoustic neuromas e. A first-degree relative with neurofibromatosis type I 9. The gene that encodes neurofibromin is found on which chromosome? a. 2 b. 6 c. 9 d. 17 e. 22 10. What is the most common site for extracutaneous involvement in children with multiple lesions like those seen in Fig 5? a. Iris b. Testis c. Kidney d. Spleen e. Central nervous system