5. Di Lernia V, Ricci C, Albertini G. Spontaneous regression of

keratoacanthoma can be promoted by topical treatment with

imiquimod cream. J Eur Acad Dermatol Venereol 2004;18:

626-9.

http://dx.doi.org/10.1016/j.jaad.2014.02.007

Overall and progression-free survival inmetastatic basosquamous cancer: A case series

To the Editor: Cutaneous basosquamous carcinoma(BSC) is a controversial histologic subtype of basalcell carcinoma (BCC),1 but is classified undersquamous cell carcinoma (SCC) by the NationalComprehensive Cancer Network due to itsaggressive clinical course.2 Surprisingly, existingoutcomes data for metastatic BSC are restricted to a

1

cm, T2 as size greater than 2 cm, T3 as bony invasionof the maxilla, orbit, or temporal bone, and T4 asbony invasion of the skeleton or perineural invasionof the base of skull. The N stage describes lymphnode (LN) involvement: N1 is defined as a singleLN metastasis less than 3 cm; N2 as metastasis at(1) a single ipsilateral LN measuring between 3 and6 cm, (2) multiple ipsilateral LN each measuring lessthan 6 cm, or (3) bilateral or contralateral LN eachmeasuring less than 6 cm; and N3 is defined asmetastasis at a single LN measuring more than 6 cm.The M stage describes presence (M1) or absence(M0) of distant metastases. Finally, an overall stage4 diagnosis requires a TNM stage of at least T4, N2,or M1.

OS and PFS were estimated by Kaplan-Meieranalysis. The date of diagnosis of stage 4 disease

reeurviv

J AM ACAD DERMATOLVOLUME 70, NUMBER 6

Letters 1145Fig 1. Overall survival and progression-fcarcinoma. Kaplan-Meier curves for overall ssmall number of case reports. We explore theoverall survival (OS) and progression-free survival(PFS) for American Joint Committee on Cancer(AJCC) Stage 4 BSC at a single large academic referralcenter in a case series of 19 patients.

Following institutional review board approval,the Stanford Cancer Center Research Databasewas queried for cases from 1997-2013. The termscutaneous and metastatic were included withsquamous cell carcinoma and/or SCC or basos-quamous, metatypical, and/or basaloid ANDsquamous to capture cases of interest. Primarycancers of noncutaneous sites were excluded.

Cases were included only if there was writtendocumentation of BSC histology by a board-certifiedpathologist and if there was stage 4 disease assessedby the TNM staging system as described in the AJCC7th edition guidelines.3 Under this classificationsystem, the T stage describes the size and/or invasionof the primary tumor: T1 is defined as size less than 2presented along with the number of patients at risintervals are represented by the shaded regions.was used as the start of follow-up for both analyses.The endpoint for OS was all-cause date of death(via medical record or Social Security Death Index).The endpoint for PFS was the earliest date ofdocumented progression of stage 4 disease (definedas enlargement, recurrence, growth of new lesions,or death). Patients alive at the data cutoff date ofJanuary 1, 2013, were right-censored. Analyses wereconducted using STATA 12 (StataCorp LP).

Nineteen cases were included in the final analysis.Ten patients were male and 17 were Caucasian.At time of stage 4 diagnosis, 5 patients had AJCCT4 disease, 6 had N2 or N3 disease, and 10 hadM1 disease.3 The most common sites of metastasiswere bone (10 patients), followed by lymph nodes(7 patients) and skull base (2 patients). After stage 4diagnosis, 10 patients underwent surgery, 9 receiveda Smoothened inhibitor, 9 received surgery withadjuvant radiation, 6 received radiation, and 6

survival of AJCC stage 4 basosquamousal (A) and progression-free survival (B) are

k at each major time point; 95% confidence

OS and PFS. The median (interquartile range)

J AM ACAD DERMATOLJUNE 2014

1146 Lettersfollow-up time was 2.9 (1.3 to 4.2) years. Eightpatients died during follow-up.

Survival analysis revealed a median OS of 6.5(95% confidence interval (CI), 3.9 toN) years and amedian PFS of 1.1 (95% CI, 0.5 to 3) years (Fig 1). Theconfidence interval for the OS included infinity as anupper bound due to a limited sample size. The 5-yearOS rate was 54% (95% CI, 19% to 80%).

This study represents an initial step in estimatingsurvival of patients with AJCC stage 4 BSC. The5-year OS rate of 54% suggests a more favorableprognosis compared with current estimates in theliterature of 17.5%, calculated from decades-old casereports of BSCs of all stages.4 Moreover, comparisonof our preliminary data to recent survival analyses ofmetastatic BCC (median OS [95% CI], 7.3 [1.6 to N]years)5 and SCC (5-year OS rate [95% CI], 11% [2% to28%])6 supports an intermediate prognosis for BSCrelative to the other cancers. Our findings contributea baseline for further investigation of survival in thisuncommon disease and provide clinicians andpatients with an estimate of disease prognosis.

Gefei Alex Zhu, BS, Christina Danial, BA, AndyLiu, BS, Shufeng Li, MS, and Anne Lynn SuChang, MD

Department of Dermatology, Stanford UniversitySchool of Medicine, Redwood City, California

Funding sources: This study was supported in partby the Stanford Center for Clinical Informatics(UL1 RR025744 from NIH/NCRR) for thedevelopment of REDCap, and the NCI CancerCenter Support Grant 5P30CA124435 andStanford NIH/NCRR CTSA Award Number UL1RR025744 for the development of the StanfordCancer Center Research Database.

Disclosure: Dr Chang has been a clinicalinvestigator for studies sponsored by Infinity,Genentech, and Novartis. Mr Zhu, Ms Danial,Mr Liu, and Ms Li declare no conflicts ofinterest.

Correspondence to: Anne Lynn Su Chang, MD,Assistant Professor of Dermatology, Departmentof Dermatology, Stanford University School ofMedicine, 450 Broadway St, Redwood City, CA94063

E-mail: alschang@stanford.edu

REFERENCESreceived chemotherapy, with no treatments affecting1. Garcia C, Poletti E, Crowson AN. Basosquamous carcinoma.

JAAD 2009;60:137-43.2. National Comprehensive Cancer Network. Basal and squamous

cell skin cancers (version 1.2013). Available from: http://www.

nccn.org/professionals/physician_gls/pdf/nmsc.pdf. Accessed

June 1, 2013.

3. AJCC Cancer Staging Handbook. 7th ed. Chicago: American

Joint Committee on Cancer; 2010.

4. Borel DM. Cutaneous basosquamous carcinoma. Review of the

literature and report of 35 cases. Arch Pathol 1973;95:293-7.

5. Danial C, Lingala B, Balise R, Oro AE, Reddy S, Colevas A, et al.

Markedly improved overall survival in 10 consecutive metasta-

tic basal cell carcinoma patients. Br J Dermatol 2013;169:673-6.

6. Brunner M, Veness MJ, Chng S, Elliott M, Clark JR. Distant

metastases from cutaneous squamous cell carcinoma

analysis of AJCC stage IV. Head Neck 2013;35:72-5.

http://dx.doi.org/10.1016/j.jaad.2014.03.003

Alopecia areata occurring during anti-TNFtherapy: A national multicenter prospectivestudy

To the Editor:Cases of alopecia areata (AA) occurringduring anti-tumor necrosis factor (TNF) treatmenthave been reported.1,2 We aimed to characterize AAduring TNF blockade and discuss the imputability ofthe drug.

From January 1, 2011, to December 31, 2012, weperformed a multicenter study asking Frenchdermatologists, rheumatologists, and gastroentero-logists to report all cases of AA occurring during anti-TNF therapy. Diagnosis of AA had to be confirmedby a dermatologist. The study was approved by theEthics Committee on Biomedical Research.

We included 29 patients with AA (17 men; meanage 39.1 years): 11 had psoriasis, 11 inflammatoryrheumatisms, and 7 inflammatory bowel diseases(Table I). Clinical presentation was predominantlypatchy AA affecting the scalp or the beard (79%).Along with AA, vitiligo, psoriasiform eruption, orHashimoto thyroiditis occurred in 7 patients (24%).Nine patients had a personal or family history of anautoimmune background with AA or vitiligo.

The mean duration of exposure to TNF blockersbefore AA development was 22.5months (range, 1 to89 months). The TNF blocker prescribed wasinfliximab (n 10), adalimumab (n 11), andetanercept (n 8). Nine patients had previouslyreceived biologics, for a mean duration of 7.5months, without exhibiting AA. All patients except2 showed good response to TNF blockers for theunderlying inflammatory disorder.

TNF blockers were withdrawn after AAappearance in 14 cases and maintained in 15. Aspecific treatment for AAwas prescribed for 71% and67% of these patients, respectively. We observedcomplete or partial recovery of AA in 76% of all cases,

with a mean time to improvement of 5 months andmean follow-up of 24 months. Patients who stopped

Overall and progression-free survival in metastatic basosquamous cancer: A case seriesReferences