Azael Freites-Martinez

Eruptive Keratoacanthomas Associated With Pembrolizumab Therapy

Importance To our knowledge, there have been no previous reports of eruptive keratoacanthomas (KAs) in patients receiving pembrolizumab. Objective To report the cases of 3 consecutive patients with pembrolizumab-induced eruptive KAs and their management. Design, Setting, and Participants Case report study of 3 patients from 2 centers with pembrolizumab-treated cancer who all developed eruptive KAs. Interventions All 3 patients had AK treatment with clobetasol ointment and intralesional triamcinolone; 2 patients also underwent open superficial cryosurgery. Results Three consecutive patients with cancer, 2 men and 1 woman (median age, 83 years; range 77-91 years), experienced pembrolizumab-associated eruptive KAs. All patients presented with a sudden onset of multiple lesions on sun-exposed areas of their extremities after a median of 13 months (range, 4-18 months) of pembrolizumab therapy. On lesional biopsy, a lichenoid infiltrate was observed in the underlying dermis, predominantly composed of CD3+ T cells, scattered CD20+ B cells, and relatively few PD-1+ (programmed cell death 1–positive) T cells, an immunophenotypic pattern also observed in other cases of anti–PD-1–induced lichenoid dermatitis. Patients were treated with clobetasol ointment and intralesional triamcinolone, alone or in combination with open superficial cryosurgery. All KAs resolved in all patients, and no new lesions occurred during close follow-up. Pembrolizumab treatment was continued without disruption in all 3 cases, and all patients had complete responses of their primary cancers. Conclusions and Relevance Pembrolizumab is used in advanced melanoma, advanced non–small-cell lung cancer, and in head and neck cancer. A variety of dermatologic immune-related adverse events including maculopapular eruption, lichenoid reactions, pruritus, and vitiligo have been described. This case series demonstrates that pembrolizumab therapy may also be associated with eruptive KAs with characteristic dermal inflammation, which improved with corticosteroid treatment (topical and intralesional) alone or in combination with cryosurgery, allowing patients to continue therapy with pembrolizumab.

Endocrine Therapy–Induced Alopecia in Patients With Breast Cancer

Importance Endocrine therapy-induced alopecia (EIA) has been anecdotally reported but not systematically described. Objective To characterize EIA in patients with breast cancer. Design, Setting, and Participants Retrospective cohort study of 112 patients with breast cancer, diagnosed with EIA from January 1, 2009, to December 31, 2016, the patients were examined at the dermatology service in a large tertiary care hospital and comprehensive cancer center. Main Outcomes and Measures The clinical features, alopecia-related quality of life (QoL), and response to minoxidil of EIA in patients with breast cancer were assessed. Data from the Hairdex Questionnaire was used to assess the impact of the alopecia on patients QoL. Higher score indicates lower QoL (0-100 score). Efficacy of minoxidil was measured at 3 or 6 months by a single-blinded investigator through standardized clinical photographs of the scalp. Results A total of 112 female patients with breast cancer were included (median [range] age, 60 [34-90] years). A total of 104 patients (93%) had standardized clinical photographs; of these, 59 patients (53%) had trichoscopy images available at baseline, and 46 patients (41%) were assessed for response to minoxidil. Alopecia was attributed to aromatase inhibitors in 75 patients (67%) and tamoxifen in 37 (33%). Severity was grade 1 in 96 of 104 patients (92%), and the pattern was similar to androgenetic alopecia. The predominant trichoscopic feature at baseline was the presence of vellus hairs and intermediate- and thick-diameter terminal hair shafts. A negative impact on QoL was reported, with a higher effect in the emotion domain according to the Hairdex score (mean [SD], 41.8 [21.3]; P < .001). After treatment with topical minoxidil, moderate or significant improvement in alopecia was observed in 37 of 46 patients (80%). Conclusions and Relevance Endocrine therapies are associated with a pattern alopecia similar to androgenetic-type, consistent with the mechanism of action of causal agents. A significant negative impact on QoL was reported by patients, despite mostly mild alopecia severity.

Ex vivo high-frequency ultrasound: A novel proposal for management of surgical margins in patients with non-melanoma skin cancer

REFERENCES 1. Greenbaum SS, Krull EA, Watnick K. Comparison of CO laser and electrosurgery in the treatment of rhinophyma. J Am Acad Dermatol. 1988;18:363-368. 2. Lim SW, Lim SW, Bekhor P. Rhinophyma: Carbon dioxide laser with computerized scanner is still an outstanding treatment. Australas J Dermatol. 2009;50:289-293. 3. Burget GC, Menick FJ. The subunit principle in nasal reconstruction. Plast Reconstr Surg. 1985;76:239-247. 4. Grattan JF. Rhinophyma, cure by plastic surgeon with a good cosmetic result. JAMA. 1920;74:1450-1452. 5. Berson MI. Rhinophyma. Plast Reconstr Surg. 1948;3:740-744.

Use of cryobiopsy in dermatological practice

SOLUTION After topical disinfection, the lesion intended to be biopsied is superficially sprayed with liquid nitrogen approximately 1 to 1.5 inches away for 4 to 5 seconds until whitening. As thawing begins, a fast shaving is done with a number 15 surgical blade on a tissue that still offers some resistance. The sample is immediately placed in formaldehyde solution. Before complete thawing, gentle pressure with a cotton swab embedded in 70% aluminium chloride solution is applied to stop any superficial bleeding (Fig 1). Postprocedure wound care is limited to daily disinfection until total healing. For protruding lesions, spraying can be substituted by using prefrozen polytetrafluoroethylene-coated tweezers. Hyperkeratotic lesions require a few extra seconds of freezing because keratin is a poor cold conductant. Cryobiopsy refers to sample removal of a previously in situ frozen tissue. It is a simple, safe, and fast technique that could replace conventional shaving biopsy. Shaving biopsy is a commonly used procedure that has the disadvantage of requiring needle prick and injection of stinging anesthetic solutions. Cryoshaving spares such need because cold acts as anesthetic. Our experience is mostly based on biopsies on multiple nonmelanoma skin cancers, warts, and actinic and seborrheic keratoses. In all cases, the material was suitable for histologic study and no artifacts were described by the pathologist, confirming the findings in other studies using frozen biopsies. Although we did not observe any pigmentation changes, the risk is not excluded. Furthermore, cryoshaving should not be used in patients with cold-triggered conditions. Any other limitations are the same as for standard shaving biopsy.

CME Part 2: Hair disorders in cancer survivors Persistent chemotherapy-induced alopecia, persistent radiotherapy-induced alopecia, and hair growth disorders related to endocrine therapy or cancer surgery

With increasing survival rates across all cancers, survivors represent a growing population that is frequently affected by persistent or permanent hair growth disorders as a result of systemic therapies, radiotherapy, surgical procedures, and therapeutic transplants. These hair disorders include persistent chemotherapy-induced alopecia, persistent radiotherapy-induced alopecia, endocrine therapy-induced alopecia and hirsutism, postsurgery alopecia and localized hypertrichosis, and persistent stem cell transplantation and targeted therapy-induced alopecia. The information contained in this continuing medical education series should facilitate a better understanding on hair disorders in cancer survivors so that adequate support and therapies may be provided.

CME Part 1: Hair disorders in cancer patients

Cytotoxic chemotherapies, molecularly targeted therapies, immunotherapies, radiotherapy, stem cell transplants, and endocrine therapies may lead to hair disorders, including alopecia, hirsutism, hypertrichosis, and pigmentary and textural hair changes. The mechanisms underlying these changes are varied and remain incompletely understood, hampering the development of preventive or therapeutic guidelines. The psychosocial impact of chemotherapy-induced alopecia has been well documented primarily in the oncology literature; however, the effect of other alterations, such as radiation-induced alopecia, hirsutism, and changes in hair color or texture on quality of life have not been described. This article reviews clinically significant therapy-related hair disorders in oncology patients, including the underlying pathophysiological mechanisms, severity grading scales, patient-reported quality of life questionnaires, management strategies, and future translational research opportunities.

Inflammatory dermatoses, infections, and drug eruptions are the most common skin conditions in hospitalized cancer patients

Background: Dermatologic conditions cause morbidity and mortality among hospitalized cancer patients. An improved understanding is critical for implementing clinical and research programs in inpatient oncodermatology. Objective: To characterize inpatient dermatology consultations at a large comprehensive cancer center. Methods: Retrospective database query of new admissions and medical record review of initial inpatient dermatology consultations comparing inpatients consulted and not consulted during January‐December 2015. Results: In total, 412 of 11,533 inpatients received 471 dermatology consultations (54% male, median age 59.5 years). Patients with hematologic cancers were 6 times more likely to receive dermatologic consultations compared with nonhematologic cancers (odds ratio 6.56, 95% confidence interval 5.35–8.05, P < .0001). Patients consulted by a dermatologist had a significantly longer length of stay than inpatients not consulted by dermatology (median 11 vs 5 days, P < .0001). Among the 645 dermatologic conditions diagnosed, the most common categories were inflammatory diseases, infections, and drug reactions; the most frequent conditions were contact dermatitis, herpes zoster, and chemotherapy‐induced drug eruptions. Limitations: The studys retrospective nature and single‐institution setting are potential limitations. Conclusion: Hematologic malignancies are a significant risk factor for dermatology inpatient consultations. A significantly longer length of stay was associated with dermatology consultations, suggesting high comorbidities in these patients. Increased dermatologic care of these inpatients might improve quality of life, dermatologic health, and ability to receive anticancer agents.

Dermatologic Adverse Events

Patients diagnosed with cancer will face various adverse events (AEs) of chemotherapy, radiation, surgery, or stem cell transplants. Numerous dermatological AEs associated with these treatments range from those with minor psychosocial impact to being potentially life-threatening. Adverse events may result in decreased quality of life and dose reduction or treatment interruption, all of which may compromise clinical outcome. A variety of adverse events such as alopecia, mucositis, hand–foot syndrome, and rashes associated with conventional cytotoxic agents have been well-described, but with the advent of novel targeted agents, new dermatologic adverse events and systemic AEs have emerged. AEs affecting the skin and its adnexa (i.e., hair, nails) such as hand–foot skin reaction, acneiform rash, and paronychia may present both diagnostic and management challenges for health-care providers. Although many antitoxicity interventions have not been investigated in randomized studies, there are ways of mitigating these untoward events in clinical practice. This chapter will address multiple skin and nail AEs induced by conventional, targeted chemotherapy agents and immunotherapies and will describe adverse effects associated with radiotherapy. Proposed underlying mechanisms will be reviewed, and special attention will be directed to management strategies that are available to date.

Nipple Adenoma: New Images and Cryosurgery Treatment

described in the literature, authors consider myoid hamartomas as adenosis with leiomyomatous myoid metaplasia of myoepithelial cells. There is a case of myoid hamartoma reported as having a chondromyxoid metaplasia and pseudoangiomatous stromal hyperplasia. We are reporting a case of myoid hamartoma with symplastic changes, not described before in the literature. Myoid hamartoma is benign but coincidental malignancy can occur. That is why total excision is the treatment of choice for this entity (Figs. 1–4).

A Painful Nipple: A Rare Presentation for an Infiltrating Lobular Carcinoma

A 65-year-old woman presented with nipple pain of 18 months of progression. She was physically examined by her gynecologist in three different visits and was followed by mammography and ultrasound explorations, all resulting negative. She decided to be examined by a dermatologist due to persistence right nipple pain. On physical examination, right nipple was discreet yellowish, infiltrated, and superficial palpation was overwhelming to the patient. There was no nipple discharge; no tumor was clearly palpable (Fig. 1). A new mammography and ultrasound was done, both reported as negative. A high resolution dermatologic ultrasound (Tpm, 22 MHz) was performed in both nipples revealing an increase in tissue density on the right one. A doppler ultrasound (9 MHz) was repeated, and showed an increase in size of the right nipple compared to the left one, with a pseudonodular and hypoechoic aspect, measuring 15.4 mm, with an increase in vascularization showing the nipple skin discretely thickened (Fig. 2). A punch biopsy was performed. Histopathology showed that dermal stroma of the nipple was infiltrated by small uniform cells with atypical nuclei, inconspicuous nucleoli, and cells with a linear “classic” growth pattern (Fig. 3). The immunohistochemical profile was estrogen and progesterone receptor positive and c-erbB2 negative. The final histologic diagnosis was infiltrating lobular carcinoma. The MRI showed a large lymph node metastasis in the right axilla (Fig. 4). CT scan did not show metastatic