Karen Y. Kuo

Incidental regression of an advanced basal cell carcinoma after ipilimumab exposure for metastatic melanoma.

Ipilimumab, an immune checkpoint inhibitor, is approved for the treatment of advanced melanoma. Its potential activity in keratinocytic cancers, however, is not well known. We present a case of a man in his 60s with advanced basal cell carcinoma (BCC) that regressed after incidental exposure to ipilimumab to treat the patients concurrent metastatic melanoma.

Correlates of multiple basal cell carcinoma in a retrospective cohort study: Sex, histologic subtypes, and anatomic distribution

To the editor: Basal cell carcinoma (BCC) is the most common malignancy in the United States. More than 41% of patients with 2 or more BCCs develop a subsequent BCC. Despite clinical awareness of risk factors for a second BCC, there remains a subset of individuals who develop significantly more BCCs than the average population. In this study, we sought to characterize the factors associatedwithhigh-frequency BCC, including sex, anatomic site, and histologic site. We performed a retrospective cohort study of all biopsy specimens of BCCs between June 2005 and May 2015 at Stanford Hospital and Clinics, comprising 4943 BCCs and affecting a total of 2407 patients. A final cohort of 1419 patients had 5 or more years of continuous follow-up at Stanford, of whom 60.7% (n1⁄4 862) weremale and 39.3% (n1⁄4 557) were female (Supplemental Table I; available at http:// www.jaad.org). During the 10-year period, 46.7% of patients (n 1⁄4 662) had 2 or more BCCs and 5% had 6 or more BCCs (termed ‘‘high-frequency BCCs’’). In our cohort, BCCs were most commonly located on the head and neck (55.7%), followed by the trunk (28.0%), the extremities (15.9%), and the genitalia (0.1%). The most common histologic subtype was nodular (57.1%), followed by superficial (19.5%) and infiltrative (14.1%). Patients with 6 or more BCCs were more likely to have BCCs on the trunk than those with a single BCC (P 1⁄4 .011). Similarly, as the number of BCCs increased, they were more likely to be of the superficial subtype as compared with the subtypes in patients with a single BCC (P1⁄4 .007). The anatomic and histologic subtype of high-frequency BCCs were consistent with prior case series on multiple BCCs. As the number of BCCs increased, the proportion of male patients increased, from 57.1% of those with 1 BCC to 62.1% with 2 to 5 BCCs to 79.3% with 6 or more BCCs (Fig 1). With the use of generalized logistic regression, adjusted for age, race, and followup duration, male sex was associatedwith a 1.18-fold increase in risk of 2 or more BCCs (P 1⁄4 .007) and a 2.40-fold increase in risk of 6 or more BCCs (P \ .001) (Table I). The increased risk of highfrequency BCCs followed a nonlinear change with each incremental BCC (Supplemental Fig 1; available at http://www.jaad.org).

Azathioprine and risk of multiple keratinocyte cancers

To the Editor: Chronic medication-induced immunosuppression is a known risk factor for keratinocyte cancer (KC). To determine which immunosuppressants are most significantly associated with increased KC, we retrospectively analyzed 3398 subjects with a biopsy finding of squamous cell cancer (SCC) or basal cell cancer (BCC) by using 8002 pathology reports at Stanford Hospital and Clinics between 2005 and 2015. We excluded reports of residual or recurrent skin cancers (Supplementary Materials and Methods; available at http://www.jaad.org). We subdivided our cohort into 3 groups on the basis of the number of KCs developed over 10 years: (1) 1 KC, (2) 2 to 5 KCs, and (3) more than 6 KCs. In the cohort, 60.1% developed 1 KC, 31.8% developed 2 to 5 KCs, and 8.1% developed 6 or more KCs. A comparable distribution was observed for BCC and SCC frequency. Overall, patients with 6 or more BCCs or SCCs represented the top 5% of the respective cohorts. A total of 572 out of 3398 subjects with KCs had 6months or more use of immunosuppressant medications, including azathioprine (n1⁄4 39), mycophenolate mofetil (n1⁄4 158), cyclosporine (n1⁄4 103), sirolimus (n1⁄4 50), and tacrolimus

Frequent basal cell cancer development is a clinical marker for inherited cancer susceptibility

Innate DNA repair mechanisms play a critical role in protecting skin keratinocytes from UV mutagenesis and skin cancer development. We hypothesized that individuals who develop frequent skin cancers may harbor germline defects in DNA repair genes and have increased predisposition to internal malignancies. We enrolled 61 patients with unusually frequent basal cell carcinoma (BCC) development, seen at Stanford Hospital and Clinics from January 2005 until December 2015, for germline analysis of 29 DNA repair genes. In parallel, a case-control retrospective review was performed to interrogate the association of malignancies with frequent BCC development in a large US medical insurance claims database (Truven), which included 13,264 individuals with 6 or more BCCs from 2007 to 2011. 19.7% of the frequent BCC cohort harbored pathogenic mutations in DNA repair genes: APC, BARD1, BRCA1, BRCA2, CDH1, CHEK2, MLH1, MSH2, MSH6, MUTYH, NBN, and PALB2. Individuals with 6 or more BCCs had an increased risk of other malignancies, with a 3.5-fold increase in the frequent BCC cohort and a 3.2-fold increase in the Truven database. Individuals who developed frequent BCCs have an increased prevalence of germline mutations in DNA repair genes and increased malignancy risk. Our data implicate frequent BCC development as an external marker of inherited cancer risk.

Limited Role of Random Skin Biopsy in the Diagnosis of Intravascular Lymphoma in Adult Patients with Hemophagocytic Lymphohistiocytosis

Background/Aims: This study examined the role of random normal skin biopsy in the diagnosis of intravascular lymphoma (IVL) in adult Western patients with clinically diagnosed hemophagocytic lymphohistiocytosis (HLH). Methods: In a retrospective chart review study, we analyzed a total of 59 skin biopsies that were performed to diagnose IVL in 21 adult patients with HLH seen at Stanford Hospital between 2004 and 2016. Results: Out of the 59 skin biopsies, 42 were taken from clinically normal-appearing skin and 17 from clinically abnormal-appearing skin. None of the 59 biopsies revealed a diagnosis of primary or metastatic malignancy, regardless of the malignancy history, clinical presentation, and biopsy and histopathologic characteristics. A review of 8 positive IVL cases at Stanford Hospital including 1 case associated with HLH showed 1 positive diagnosis by a targeted skin biopsy and other positive diagnoses by bone marrow (n = 4), lung (n = 2), brain (n = 2), muscle (n = 1), and nerve (n = 1). Conclusion: Random skin biopsies have a limited role in diagnosing IVL in adult patients with HLH, in the setting of a single academic institution in the USA. A review of the literature emphasizes the role of a full body skin exam with a selective skin biopsy in these patients.