Diagnosis in Oncology

2. Heng Y, Schuffler MD, Haggitt RC, et al: Pneumatosis intestinalis: A review.
Am J Gastroenterol 90:1747-1758, 1995
3. Slavin R, Dias M, Saral R: Cytosine arabinoside induced gastrointestinal
toxic alteration in sequential chemotherapy protocols: A clinical-pathologic study
of 33 patients. Cancer 42:1747-1759, 1978
4. Pestalozzi BC, Sotos GA, Choyke PL, et al: Typhlitis resulting from treat-
ment with taxol and doxorubicin in patients with metastatic breast cancer. Cancer
71:1797-1800, 1993
5. Candelaria M, Bourlon-Cuellar R, Zubieta JL, et al: Gastrointestinal
pneumatosis after docetaxel chemotherapy. J Clin Gastroenterol 34:444-445,
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after chemotherapy for hematological malignancies: Report of 4 cases. Intern
Med 34:212-215, 1995
DOI: 10.1200/JCO.2006.10.5742

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Acquired Hypertrichosis Lanuginosa: A Rare

Cutaneous Paraneoplastic Syndrome
A 57-year-old woman with a history of carcinoma of the
breast presented with fine, lanugo-type hair on the cheeks and
chin. Infiltrating ductal carcinoma of the right breast
(pT1N1M0, estrogen receptor positive, and progesterone re-
ceptor positive) had been diagnosed 5 years before presentation
and was treated by modified radical mastectomy with total
axillary lymph node dissection and adjuvant tamoxifen. One
year after surgery a local recurrence was excised and irradiated
and tamoxifen was replaced with letrozole. In the subsequent 2
years, she developed metastatic disease in subclavicular and
contralateral axillary lymph nodes, bone, and liver for which she
received six cycles of cyclophosphamide, methotrexate, and
fluorouracil followed by several hormone therapies. Because of
progressive disease 6 months after the completion of therapy,
she was treated with six cycles of doxorubicin. Three months
thereafter she presented with excessive fine, unmedullated hair
Fig 2.
on her cheeks and chin (Figs 1 and 2). In addition, progression of
supra- and infraclavicular and contralateral axillary lymphadenopa-
thy were noted. No signs of virilization or hirsutism were seen and
axillary and pubic hair appeared normal. Laboratory investigations, nosa acquisita was diagnosed. Computed tomography scan of the
including extensive endocrinologic studies, did not reveal any abnor- thorax confirmed progression of lymphangitis carcinomatosa and
malities other than a previously recognized elevation in liver function clavicular and contralateral axillary lymphadenopathy. With do-
tests, most probably caused by liver metastases. Hypertrichosis lanugi- cetaxel and local radiotherapy, a partial response was obtained and
coincided with disappearance of the hypertrichosis. Our patient
passed away within 2 years after diagnosing this rare cutaneous para-
neoplastic syndrome.
Cutaneous paraneoplastic syndromes are often misinterpreted as
cutaneous metastases or not recognized as a marker of internal malig-
nancy. In the currently reported case, hypertrichosis developed during
progression of known metastatic disease. In general, these cutaneous
syndromes run a parallel course with the tumor, disappearing when
the primary tumor is removed and reappearing with local recurrence
or distant metastases.1
Acquired hypertrichosis lanuginosa (AHL) is a rare cuta-
neous paraneoplastic syndrome characterized by the develop-
ment of excessive, long, fine, nonpigmented hairs, preferentially
located on the face.2,3 So far, only 56 cases of AHL have been
reported,2-7 of which five cases were associated with breast
carcinoma. AHL is most commonly associated with adenocar-
cinoma of the lung and colon (27% and 24%, respectively1,4,5),
and is also described in other solid tumors of the pancreas,
uterus, ovary, kidney, bladder, and gallbladder in addition to
leukemia and Ewing’s sarcoma. The syndrome is more often
observed in women than in men (70% and 30%, respectively)3,4
and usually occurs when the tumor is disseminated.8 In women,
Fig 1. AHL should be differentiated from hirsutism, a subclass of

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Copyright © 2022 American Society of Clinical Oncology. All rights reserved.
 Vulink and Huinink
hypertrichosis defined by excessive androgen-sensitive hair
growth distributed in an adult male pattern.9 The differential
diagnosis includes other causes of acquired hypertrichosis, such
as anorexia nervosa, AIDS, brain injury, hypothyroidism, poly-
myositis, porphyria cutanea tarda, primary biliary cirrhosis,
shock, systemic lupus erythematosus, and specific drugs (corti-
costeroids, cyslosporine, diazoxide, interferon-␣, minoxidil, penicillin,
phenytoin, spironolactone, streptomycin, and zidovudine).2,3,5,10-12 In
these associated cases, hypertrichosis is characterized by terminal-type
hair, which is mostly coarse and dark.2,8
Our patient had normal adrenal and thyroid function and
was not using any of the aforementioned drugs. She had been
treated with doxorubicin a few months before presentation with
hypertrichosis. Gaffney et al12 suggest that cytotoxic chemother-
apy itself might induce AHL, but in the majority of reported
cases no association has been described. In our patient the
lanugo-type hair disappeared during docetaxel treatment to-
gether with regression of metastasis.
The mechanism responsible for excessive lanugo-type hair
growth is still unclear.2,3 It has been suggested that an as yet unidenti-
fied tumor-derived humoral factor may lead to a prolongation of the
anagen phase (the active growth phase) of vellus hair follicles, resulting
in hypertrichosis.3,13
AHL is commonly associated with symptoms like burning glos-
sitis, papillary hypertrophy of the tongue, taste or smell disturbances,
diarrhea, lymphadenopathy, and weight loss.4,14 Our patient pre-
sented with abnormal hair growth and progressive lymphadenopathy;
however, no other clinical features were noted.
Although higher levels of gonadotropin, carcinoembryonic anti-
gen, and urinary cortisol were found in some patients, no consistent
biochemical abnormalities have been reported.2,8
The occurrence of AHL is usually associated with a poor progno-
sis, as most patients succumb within 3 years of initial diagnosis.3
Treatment of AHL is focused on eradication of the cause, which
frequently results in its resolution. In our patient, a partial regression
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Copyright © 2022 American Society of Clinical Oncology. All rights reserved.
of metastasis was noted during second-line chemotherapy together
with the disappearance of hypertrichosis.
Annelie J.E. Vulink and Daan ten Bokkel Huinink
Diakonessenhuis Utrecht, Department of Internal Medicine, Division of
Medical Oncology, Utrecht, the Netherlands
© 2007 by American Society of Clinical Oncology
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The authors indicated no potential conflicts of interest.
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DOI: 10.1200/JCO.2007.10.6963
JOURNAL OF CLINICAL ONCOLOGY