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Acquired hypertrichosis lanuginosa as a presenting sign of metastatic prostate cancer with rapid resolution after treatment
Acquired hypertrichosis lanuginosa as a presenting sign of metastatic prostate cancer with rapid resolution after treatment Julie P. Wyatt, MD,a Heidi F. Anderson, BS,b Kenneth E. Greer, MD,a and Kelly M. Cordoro, MDa Charlottesville, Virginia Background: Acquired hypertrichosis lanuginosa (AHL) is a rare cutaneous disorder that involves spontaneous growth of lanugo-type hair in association with overt or occult malignant neoplasms. Bronchopulmonary and gastrointestinal malignancies are most commonly associated. Case Presentation: We report the occurrence of AHL associated with metastatic prostate cancer and its abrupt resolution after bilateral orchiectomy. To our knowledge, this is the first reported case of an association with prostate cancer. Limitations: The case presented represents a single patient; therefore, the findings and results reported may not be applicable to all patient populations. Conclusion: A variety of cutaneous findings are considered warning indicators of underlying neoplastic disease. Physician awareness of such signs can prompt timely and potentially life-saving investigations and interventions. AHL is regarded as such a sign. Physician awareness of the addition of prostate cancer to the growing list of AHL-associated malignancies provides rationale for appropriate testing and referral. ( J Am Acad Dermatol 2007;56:S45-7.)
A
cquired hypertrichosis lanuginosa (AHL) is a rare cutaneous disorder that involves spontaneous growth of lanugo-type hair often confined to the skin of the neck and face, although it may affect any hair-bearing area. This clinical finding was first described by Turner1 in 1865 in a 42-yearold woman with breast cancer. It has since been descriptively termed ‘‘malignant down’’ reflecting its common association with advanced neoplasms.2 We report a case of a 93-year-old man with metastatic prostate cancer who was noted to have growth of fine lanugo hair on his face and shoulders. Using the National Library of Medicine’s database, a review of the literature yielded approximately 50 cases of malignancy-associated AHL and, to our knowledge,
From the Department of Dermatologya and School of Medicine,b University of Virginia. Funding sources: None. Conflicts of interest: None identified. Reprint requests: Kelly M. Cordoro, MD, Box 800718, University of Virginia Health System, Charlottesville, VA 22908. E-mail: [email protected]. 0190-9622/$32.00 ª 2007 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2006.07.011
this is the first reported case of AHL associated with metastatic prostate cancer. This case serves to raise physician awareness of this paraneoplastic phenomenon, as it can present before, with, or after the malignancy.
CASE REPORT A 93-year-old Caucasian man with a 7-year history of stable chronic lymphocytic leukemia presented to a gastroenterologist in February 2000 for evaluation of chronic diarrhea, bloating, and fecal incontinence. He reported a 30-lb weight loss, decreased appetite, and a persistent bitter taste in his mouth. At this time, increased hair growth was noted on the face. The patient reported that he had first noticed a change in the amount and texture of facial hair 2 months prior to this visit. In the initial workup of his diarrhea, a computed tomography scan of the abdomen and pelvis showed an abnormal bladder and prostate with thickening of the rectal wall. An abdominal radiograph revealed multiple sclerotic lesions in the pelvis, sacrum, and vertebral bodies consistent with metastatic prostate cancer. The cause of his diarrhea remained unknown after multiple imaging studies, biopsy specimens, and laboratory tests. S45
S46 Wyatt et al
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Fig 2. Acquired lanugo hair on shoulder and back of patient with metastatic prostate cancer.
Fig 1. Abundant lanugo hair on face of man with underlying metastatic prostate cancer.
The dermatology department was consulted to evaluate the increased facial hair. The patient again described dysgeusia in addition to the hair growth. His medical history included stable B-cell chronic lymphocytic leukemia, hypothyroidism, coronary artery disease, hypertension, hypercholesterolemia, chronic cervical arthritis, cataracts, eczema, and an atypical villous adenoma treated with a right hemicolectomy. Medications included atenolol, isosorbide mononitrate, furosemide, aspirin, levothyroxine, pancrelipase, and a fiber supplement. Physical examination revealed an alert and pleasant gentleman with a striking increase of fine white hair over much of his face and shoulders (Figs 1 and 2). His tongue was red and fissured. The scalp, pubic, and axillary hair was normal. Laboratory results revealed normal B12, folate, androgen, and cortisol levels. Vital signs were normal. A diagnosis of malignancy-associated AHL was rendered. At a follow-up appointment 2 years later in February 2002, the patient noted that he had undergone a bilateral orchiectomy as therapy for the prostate cancer. All of the lanugo hair disappeared within weeks after this treatment (Fig 3). According to patient reports documented in the medical record, the urology team who cared for him noted clinical and radiographic evidence of tumor regression after the orchiectomy, coinciding temporally with the onset of resolution of the lanugo hair. The hair growth did not reappear for the remainder of his life. The patient died of a myocardial infarction in July 2002.
Fig 3. Resolution of lanugo hair after bilateral orchiectomy.
DISCUSSION AHL is a poorly understood paraneoplastic condition characterized by the spontaneous development of lanugo-type hair. The face, trunk, and limbs are most often affected whereas the palms, soles, and suprapubic and genital areas are usually spared.3,4 Approximately 50 cases of AHL have been reported with the most common associated neoplasms being bronchopulmonary (32%) and gastrointestinal (26%). Other reported neoplasms include carcinomas of the breast, uterus, bladder, ovary, gallbladder, pancreas, liver, kidney, and parotid gland, and lymphoma, leukemia, melanoma, and Ewing’s sarcoma.5-7 Associated symptoms such as burning glossitis, lingual papillary hypertrophy, oral hyperpigmentation, trichomegaly, disturbances of taste and smell, diarrhea, adenopathy, and weight loss have been reported.6,8
J AM ACAD DERMATOL
Wyatt et al S47
VOLUME 56, NUMBER 2
Dermatologic findings reported in association with AHL include scleroderma, seborrheic keratoses, florid cutaneous papillomatosis, acanthosis nigricans,9-11 and palmar and plantar hyperkeratosis.3,11,12 It is unclear whether the variable clinical presentation can be attributed to differences in tumor type, degree of differentiation, or host responses.12 The mechanism causing the mature hair follicle to revert and produce embryonic hair is not completely understood although it has been proposed that secretion of humoral substances by cancer cells may account for its development.8,11,13 Several aberrant laboratory values including elevated carcinoembryonic antigen, gonadotropin, serum gastrin, serum calcium, urinary cortisol, and low testosterone have been reported in association with AHL although without consistent explanation.11 Differential diagnoses for suggested AHL include hirsutism and hypertrichosis associated with nonmalignant causes. Systemic diseases causing hypertrichosis include porphyria, thyroid disease, acrodynia, juvenile dermatomyositis, malabsorption, and POEMS syndrome. Central nervous systemerelated causes include encephalitis, head trauma, multiple sclerosis, shock, anorexia, and hyperostosis interna.14 Common pharmacologic causes are minoxidil, diazoxide, phenytoin, cyclosporin A, psoralen-UVA, prednisolone, streptomycin, acetazolamide, benoxaprofen, penicillamine, and fenoterol.11,15 Our patient had no relevant drug exposures, endocrine abnormalities, or other known conditions to account for his abrupt onset of hypertrichosis. AHL is an obligatory marker of an underlying malignancy although it is usually recognized in metastasizing or late carcinomas.4,16 Hovenden14 reports 29 of 34 cases (85%) of AHL to be late markers for occult malignancy. Its occurrence is associated with a poor prognosis with most patients living less than 3 years after the initial diagnosis. In fact, the maximum survival recorded is 61 months after the appearance of AHL.3 However, AHL may precede the diagnosis of the underlying malignancy by up to 2 years.4 Wadskov et al17 reported a patient being followed up for AHL, glossitis, weight loss, and fatigue. The initial malignancy workup revealed negative findings but approximately 20 months later she was found to have a rapidly growing tumor of the right breast. Kassis et al18 reported the case of a patient who had AHL with multiple malignancies. AHL followed the therapy of the first malignancy by
9 months and antedated the second malignancy by 4 to 6 months. This case underscores the need for an aggressive search for occult or persistent malignancy despite the apparent cure of the primary tumor. The recognition of AHL as a paraneoplastic phenomenon necessitates appropriate diagnostic evaluations in patients given the diagnosis of this entity. The addition of metastatic prostate cancer to the growing list of AHL-associated malignancies provides rationale for appropriate testing and referral. REFERENCES 1. Turner M. Case of a woman whose face and body in two or three weeks’ time became covered with a thick crop of short and white downy hair. Med Times Gazette 1865;2:507. 2. Fretzin DF. Malignant down. Arch Dermatol 1967;95:294-7. 3. Hovendon AL. Hypertrichosis lanuginosa acquisita associated with malignancy. Clin Dermatol 1993;11:99-106. 4. Dyall-Smith D, Varigos G, Thomas R. Hypertrichosis lanuginosa acquisita and adenocarcinoma of the colon. Australas J Dermatol 1987;28:1-6. 5. Begany A, Nagy-Vezekenyi K. Hypertrichosis lanuginose acquisita. Acta Derm Venereol 1992;72:18-9. 6. Duncan LE, Hemming JD. Renal cell carcinoma of the kidney and hypertrichosis lanuginosa acquisita. Br J Urol 1994;74: 678-9. 7. Price ML, Hall-Smith SP. Hypertrichosis lanuginosa acquista. Clin Exp Dermatol 1985;10:255-7. 8. Velez A, Kindelan JM, Garcia-Herola A, Garcia-Lazaro M, Sanchez-Guijo P. Acquired trichomegaly and hypertrichosis in metastatic adenocarcinoma. Clin Exp Dermatol 1995;20: 237-9. 9. Worret WI, Mayerhaousen W, Emslander HP. Hypertrichosis lanuginosa acquisita associated with florid cutaneous papillomatosis. Int J Dermatol 1993;32:56-8. 10. Hensley GT, Gynn KP. Hypertrichosis lanuginosa as a sign of internal malignancy. Cancer 1969;24:1051-6. 11. Farina MC, Tarin N, Grilli R. Acquired hypertrichosis lanuginosa: case report and review of the literature. J Surg Oncol 1998;68: 199-203. 12. Jemec GBE. Hypertrichosis lanuginosa acquisita: report of a case and review of the literature. Arch Dermatol 1986;122: 805-8. 13. Van der Lught D, De wit CD. Hypertrichosis lanuginosa acquisita. Dermatologica 1973;146:46-54. 14. Tru¨eb RM. Causes and management of hypertrichosis. Am J Clin Dermatol 2002;3:617-27. 15. Hovenden AL. Acquired hypertrichosis lanuginosa associated with malignancy. Arch Intern Med 1987;147:2013-8. 16. Mengori P, Rosales O. Hypertrichosis lanuginosa in a man with colon adenocarcinoma. Arch Intern Med 1989;149:471. 17. Wadskov S, Bro-Jorgensen A, Sondergarard J. Acquired hypertrichosis lanuginose: a skin marker of internal malignancy. Arch Dermatol 1976;112:1442-4. 18. Kassis V, Kassis E, Keiding L, Thomsen HK. Hypertrichosis lanuginosa acquisita associated with multiple malignancies. J Am Acad Dermatol 1985;12:1106-7.
A
cquired hypertrichosis lanuginosa (AHL) is a rare cutaneous disorder that involves spontaneous growth of lanugo-type hair often confined to the skin of the neck and face, although it may affect any hair-bearing area. This clinical finding was first described by Turner1 in 1865 in a 42-yearold woman with breast cancer. It has since been descriptively termed ‘‘malignant down’’ reflecting its common association with advanced neoplasms.2 We report a case of a 93-year-old man with metastatic prostate cancer who was noted to have growth of fine lanugo hair on his face and shoulders. Using the National Library of Medicine’s database, a review of the literature yielded approximately 50 cases of malignancy-associated AHL and, to our knowledge,
From the Department of Dermatologya and School of Medicine,b University of Virginia. Funding sources: None. Conflicts of interest: None identified. Reprint requests: Kelly M. Cordoro, MD, Box 800718, University of Virginia Health System, Charlottesville, VA 22908. E-mail: [email protected]. 0190-9622/$32.00 ª 2007 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2006.07.011
this is the first reported case of AHL associated with metastatic prostate cancer. This case serves to raise physician awareness of this paraneoplastic phenomenon, as it can present before, with, or after the malignancy.
CASE REPORT A 93-year-old Caucasian man with a 7-year history of stable chronic lymphocytic leukemia presented to a gastroenterologist in February 2000 for evaluation of chronic diarrhea, bloating, and fecal incontinence. He reported a 30-lb weight loss, decreased appetite, and a persistent bitter taste in his mouth. At this time, increased hair growth was noted on the face. The patient reported that he had first noticed a change in the amount and texture of facial hair 2 months prior to this visit. In the initial workup of his diarrhea, a computed tomography scan of the abdomen and pelvis showed an abnormal bladder and prostate with thickening of the rectal wall. An abdominal radiograph revealed multiple sclerotic lesions in the pelvis, sacrum, and vertebral bodies consistent with metastatic prostate cancer. The cause of his diarrhea remained unknown after multiple imaging studies, biopsy specimens, and laboratory tests. S45
S46 Wyatt et al
J AM ACAD DERMATOL FEBRUARY 2007
Fig 2. Acquired lanugo hair on shoulder and back of patient with metastatic prostate cancer.
Fig 1. Abundant lanugo hair on face of man with underlying metastatic prostate cancer.
The dermatology department was consulted to evaluate the increased facial hair. The patient again described dysgeusia in addition to the hair growth. His medical history included stable B-cell chronic lymphocytic leukemia, hypothyroidism, coronary artery disease, hypertension, hypercholesterolemia, chronic cervical arthritis, cataracts, eczema, and an atypical villous adenoma treated with a right hemicolectomy. Medications included atenolol, isosorbide mononitrate, furosemide, aspirin, levothyroxine, pancrelipase, and a fiber supplement. Physical examination revealed an alert and pleasant gentleman with a striking increase of fine white hair over much of his face and shoulders (Figs 1 and 2). His tongue was red and fissured. The scalp, pubic, and axillary hair was normal. Laboratory results revealed normal B12, folate, androgen, and cortisol levels. Vital signs were normal. A diagnosis of malignancy-associated AHL was rendered. At a follow-up appointment 2 years later in February 2002, the patient noted that he had undergone a bilateral orchiectomy as therapy for the prostate cancer. All of the lanugo hair disappeared within weeks after this treatment (Fig 3). According to patient reports documented in the medical record, the urology team who cared for him noted clinical and radiographic evidence of tumor regression after the orchiectomy, coinciding temporally with the onset of resolution of the lanugo hair. The hair growth did not reappear for the remainder of his life. The patient died of a myocardial infarction in July 2002.
Fig 3. Resolution of lanugo hair after bilateral orchiectomy.
DISCUSSION AHL is a poorly understood paraneoplastic condition characterized by the spontaneous development of lanugo-type hair. The face, trunk, and limbs are most often affected whereas the palms, soles, and suprapubic and genital areas are usually spared.3,4 Approximately 50 cases of AHL have been reported with the most common associated neoplasms being bronchopulmonary (32%) and gastrointestinal (26%). Other reported neoplasms include carcinomas of the breast, uterus, bladder, ovary, gallbladder, pancreas, liver, kidney, and parotid gland, and lymphoma, leukemia, melanoma, and Ewing’s sarcoma.5-7 Associated symptoms such as burning glossitis, lingual papillary hypertrophy, oral hyperpigmentation, trichomegaly, disturbances of taste and smell, diarrhea, adenopathy, and weight loss have been reported.6,8
J AM ACAD DERMATOL
Wyatt et al S47
VOLUME 56, NUMBER 2
Dermatologic findings reported in association with AHL include scleroderma, seborrheic keratoses, florid cutaneous papillomatosis, acanthosis nigricans,9-11 and palmar and plantar hyperkeratosis.3,11,12 It is unclear whether the variable clinical presentation can be attributed to differences in tumor type, degree of differentiation, or host responses.12 The mechanism causing the mature hair follicle to revert and produce embryonic hair is not completely understood although it has been proposed that secretion of humoral substances by cancer cells may account for its development.8,11,13 Several aberrant laboratory values including elevated carcinoembryonic antigen, gonadotropin, serum gastrin, serum calcium, urinary cortisol, and low testosterone have been reported in association with AHL although without consistent explanation.11 Differential diagnoses for suggested AHL include hirsutism and hypertrichosis associated with nonmalignant causes. Systemic diseases causing hypertrichosis include porphyria, thyroid disease, acrodynia, juvenile dermatomyositis, malabsorption, and POEMS syndrome. Central nervous systemerelated causes include encephalitis, head trauma, multiple sclerosis, shock, anorexia, and hyperostosis interna.14 Common pharmacologic causes are minoxidil, diazoxide, phenytoin, cyclosporin A, psoralen-UVA, prednisolone, streptomycin, acetazolamide, benoxaprofen, penicillamine, and fenoterol.11,15 Our patient had no relevant drug exposures, endocrine abnormalities, or other known conditions to account for his abrupt onset of hypertrichosis. AHL is an obligatory marker of an underlying malignancy although it is usually recognized in metastasizing or late carcinomas.4,16 Hovenden14 reports 29 of 34 cases (85%) of AHL to be late markers for occult malignancy. Its occurrence is associated with a poor prognosis with most patients living less than 3 years after the initial diagnosis. In fact, the maximum survival recorded is 61 months after the appearance of AHL.3 However, AHL may precede the diagnosis of the underlying malignancy by up to 2 years.4 Wadskov et al17 reported a patient being followed up for AHL, glossitis, weight loss, and fatigue. The initial malignancy workup revealed negative findings but approximately 20 months later she was found to have a rapidly growing tumor of the right breast. Kassis et al18 reported the case of a patient who had AHL with multiple malignancies. AHL followed the therapy of the first malignancy by
9 months and antedated the second malignancy by 4 to 6 months. This case underscores the need for an aggressive search for occult or persistent malignancy despite the apparent cure of the primary tumor. The recognition of AHL as a paraneoplastic phenomenon necessitates appropriate diagnostic evaluations in patients given the diagnosis of this entity. The addition of metastatic prostate cancer to the growing list of AHL-associated malignancies provides rationale for appropriate testing and referral. REFERENCES 1. Turner M. Case of a woman whose face and body in two or three weeks’ time became covered with a thick crop of short and white downy hair. Med Times Gazette 1865;2:507. 2. Fretzin DF. Malignant down. Arch Dermatol 1967;95:294-7. 3. Hovendon AL. Hypertrichosis lanuginosa acquisita associated with malignancy. Clin Dermatol 1993;11:99-106. 4. Dyall-Smith D, Varigos G, Thomas R. Hypertrichosis lanuginosa acquisita and adenocarcinoma of the colon. Australas J Dermatol 1987;28:1-6. 5. Begany A, Nagy-Vezekenyi K. Hypertrichosis lanuginose acquisita. Acta Derm Venereol 1992;72:18-9. 6. Duncan LE, Hemming JD. Renal cell carcinoma of the kidney and hypertrichosis lanuginosa acquisita. Br J Urol 1994;74: 678-9. 7. Price ML, Hall-Smith SP. Hypertrichosis lanuginosa acquista. Clin Exp Dermatol 1985;10:255-7. 8. Velez A, Kindelan JM, Garcia-Herola A, Garcia-Lazaro M, Sanchez-Guijo P. Acquired trichomegaly and hypertrichosis in metastatic adenocarcinoma. Clin Exp Dermatol 1995;20: 237-9. 9. Worret WI, Mayerhaousen W, Emslander HP. Hypertrichosis lanuginosa acquisita associated with florid cutaneous papillomatosis. Int J Dermatol 1993;32:56-8. 10. Hensley GT, Gynn KP. Hypertrichosis lanuginosa as a sign of internal malignancy. Cancer 1969;24:1051-6. 11. Farina MC, Tarin N, Grilli R. Acquired hypertrichosis lanuginosa: case report and review of the literature. J Surg Oncol 1998;68: 199-203. 12. Jemec GBE. Hypertrichosis lanuginosa acquisita: report of a case and review of the literature. Arch Dermatol 1986;122: 805-8. 13. Van der Lught D, De wit CD. Hypertrichosis lanuginosa acquisita. Dermatologica 1973;146:46-54. 14. Tru¨eb RM. Causes and management of hypertrichosis. Am J Clin Dermatol 2002;3:617-27. 15. Hovenden AL. Acquired hypertrichosis lanuginosa associated with malignancy. Arch Intern Med 1987;147:2013-8. 16. Mengori P, Rosales O. Hypertrichosis lanuginosa in a man with colon adenocarcinoma. Arch Intern Med 1989;149:471. 17. Wadskov S, Bro-Jorgensen A, Sondergarard J. Acquired hypertrichosis lanuginose: a skin marker of internal malignancy. Arch Dermatol 1976;112:1442-4. 18. Kassis V, Kassis E, Keiding L, Thomsen HK. Hypertrichosis lanuginosa acquisita associated with multiple malignancies. J Am Acad Dermatol 1985;12:1106-7.