Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma.

To define the cellular composition and architecture of cutaneous squamous cell carcinoma (cSCC), we combined single-cell RNA sequencing with spatial transcriptomics and multiplexed ion beam imaging from a series of human cSCCs and matched normal skin. cSCC exhibited four tumor subpopulations, three recapitulating normal epidermal states, and a tumor-specific keratinocyte (TSK) population unique to cancer, which localized to a fibrovascular niche. Integration of single-cell and spatial data mapped ligand-receptor networks to specific cell types, revealing TSK cells as a hub for intercellular communication. Multiple features of potential immunosuppression were observed, including T regulatory cell (Treg) co-localization with CD8 T cells in compartmentalized tumor stroma. Finally, single-cell characterization of human tumor xenografts and in vivo CRISPR screens identified essential roles for specific tumor subpopulation-enriched gene networks in tumorigenesis. These data define cSCC tumor and stromal cell subpopulations, the spatial niches where they interact, and the communicating gene networks that they engage in cancer.

CAPABLE: A Scoring System Utilizing Patient-Reported Measures to Evaluate Patient Experience After Mohs Surgery.

BACKGROUND: Patient experience metrics are gaining prominence in health care. We introduce the CAPABLE survey to assess postoperative experiences of Mohs surgery patients. OBJECTIVE: We sought to determine whether CAPABLE scores aligned with overall patient satisfaction in Mohs surgery. METHODS: This was a cross-sectional, survey-based study of patients presenting for their first postoperative visit after Mohs surgery. The CAPABLE survey included questions on postoperative instructions, activity limitations, pain control, provider accessibility, and bleeding, followed by 2 overall satisfaction questions taken from the Outpatient and Ambulatory Surgery Consumer Assessment of Healthcare Providers and Systems survey. The pilot study took place at the University of Texas Dell Medical School (DMS), followed by a validation study ( n = 206) at DMS and Oregon Health and Science University (OHSU). We assessed for correlations between CAPABLE scores and overall satisfaction. RESULTS: In the pilot study ( n = 137), overall CAPABLE scores and scores of individual CAPABLE components correlated positively with overall satisfaction.In the multisite validation study ( n = 206) spanning DMS and OHSU, CAPABLE scores correlated positively with overall satisfaction. CONCLUSION: The CAPABLE survey is a concise tool for assessing specific, actionable components of the postoperative patient experience in Mohs surgery, while correlating with overall patient satisfaction.

CALML5 is a ZNF750- and TINCR-induced protein that binds stratifin to regulate epidermal differentiation.

Outward migration of epidermal progenitors occurs with induction of hundreds of differentiation genes, but the identities of all regulators required for this process are unknown. We used laser capture microdissection followed by RNA sequencing to identify calmodulin-like 5 (CALML5) as the most enriched gene in differentiating outer epidermis. CALML5 mRNA was up-regulated by the ZNF750 transcription factor and then stabilized by the long noncoding RNA TINCR. CALML5 knockout impaired differentiation, abolished keratohyalin granules, and disrupted epidermal barrier function. Mass spectrometry identified SFN (stratifin/14-3-3σ) as a CALML5-binding protein. CALML5 interacts with SFN in suprabasal epidermis, cocontrols 13% of late differentiation genes, and modulates interaction of SFN to some of its binding partners. A ZNF750-TINCR-CALML5-SFN network is thus essential for epidermal differentiation.

The superiorly based bilobed flap for nasal reconstruction.

BACKGROUND: The laterally based bilobed flap is commonly used for the reconstruction of small- to medium-sized defects of the distal portion of the nose; However, when this flap is used to repair defects that are larger, more cephalic, or more lateral on the nose, there is a risk for lower nasal distortion. Reorienting the base superiorly preserves the advantages of the traditional design while minimizing this risk. OBJECTIVE: To demonstrate the design, execution, and efficacy of the superiorly based bilobed flap. METHODS: A retrospective review examined all superiorly based bilobed flaps performed by 1 surgeon (J.C.) in 2000-2016 after tumor extirpation by Mohs micrographic surgery at a single institution. RESULTS: A total of 41 surgical defects were closed with 40 flaps between June 2000 and August 2016 (1 patient had 2 defects closed with a single flap). Of the tumors, 55% were located on the nasal dorsum, and the median of the longest postoperative tumor axis was 1.4 cm. Follow-up was available for 40 flaps, and no infections, hematomas, or episodes of full-thickness necrosis were observed. LIMITATIONS: Data were collected retrospectively from a single institution without a standardized assessment tool for aesthetic outcomes. CONCLUSION: The superiorly based bilobed flap is useful for nasal reconstruction.

The Nasal Tip Rotation Flap for Reconstruction of the Lateral Nasal Tip, Anterior Ala, and Soft Triangle: The Authors' Experience With 55 Patients.

BACKGROUND: Defects of the lateral nasal tip, anterior ala, and soft triangle subunits lack reconstructive options that are consistently satisfactory. For such defects, the novel anterior-based nasal tip rotation flap provides functional and aesthetic results in a single operative session. OBJECTIVE: To describe the authors' experience with the nasal tip rotation flap, including patient selection and design modifications to enhance aesthetic success. METHODS: An IRB-approved retrospective database review of nasal tip rotation flap repairs was performed at the Medical University of South Carolina and Stanford University Medical Center. The design and surgical technique of this flap are described and illustrated, emphasizing factors such as nasal shape and defect location in modifying flap design. RESULTS: The nasal tip rotation is a single-stage, local flap that provides optimal tissue match with recapitulation of the native topography of the nasal tip and incision lines that are well hidden at the junction of cosmetic subunits. The mechanics of the flap distribute closure tension widely across the alar rim without focal notching or airway compromise. CONCLUSION: The nasal tip rotation flap is a reliable, cosmetically elegant repair that fills a gap in the reconstructive options for anterior ala and soft triangle defects on the nose.

Management of High-Risk Squamous Cell Carcinoma of the Skin.

OPINION STATEMENT: Non-melanoma skin cancer (NMSC) is the most common malignancy in the USA, with cutaneous squamous cell carcinomas (cSCCs) constituting approximately 20 % of all NMSC. While cSCCs typically behave in an indolent fashion and can be cured with local destructive or surgical methods, a small subset metastasizes and induces significant morbidity and mortality. Identifying and aggressively treating these "high-risk" cSCCs (HRcSCCs) is thus paramount. Recent improvements in staging cSCCs appear to offer better risk stratification than earlier staging criteria. Radiologic imaging and sentinel lymph node biopsy may be beneficial in certain cases of HRcSCC, although more studies are needed before these techniques should be uniformly incorporated into management. Surgery with complete margin control, such as that offered by the Mohs micrographic technique, represents the first-line treatment for these tumors. Radiation therapy is likely most beneficial in the adjuvant setting. Chemotherapy is typically best reserved for patients with metastatic or locally advance disease that is not controllable with surgical and/or radiation therapies. Newer targeted treatments, such as EGFR inhibitors and immunotherapies may offer greater efficacy in these settings, although further evaluation is needed.

Lack of efficacy with 1064-nm neodymium:yttrium-aluminum-garnet laser for the treatment of onychomycosis: a randomized, controlled trial.

BACKGROUND: Laser therapies have been Food and Drug Administration approved for temporary nail plate clearance; however, there is minimal evidence of their long-term efficacy. OBJECTIVE: We sought to evaluate the clinical and mycological clearance of toenails treated with 1064-nm neodymium:yttrium-aluminum-garnet laser versus no treatment. METHODS: This was a randomized, controlled, single-center trial comparing 2 treatments with 1064-nm neodymium:yttrium-aluminum-garnet laser (fluence of 5 J/cm(2), rate of 6 Hz) spaced 2 weeks apart versus no treatment in 27 patients (N = 125 affected nails) with clinical and mycological diagnosis of onychomycosis. At 3 months, patients were assessed with mycological cultures and proximal nail plate measurements. Patients treated with laser were also assessed with proximal nail plate measurements at 12 months. RESULTS: At 3 months, 33% of patients treated with laser achieved a negative mycological culture compared with 20% of the control group (P = .49), and had more proximal nail plate clearance compared with control subjects (0.44 vs 0.15 mm, P = .18), which was not statistically significant. At 12 months, there was no difference in nail plate clearance between laser versus control subjects (0.24 vs 0.15 mm, P = .59). LIMITATIONS: Our study was limited by the small sample size and number of treatments. CONCLUSIONS: There was no significant mycological culture or clinical nail plate clearance with 1064-nm neodymium:yttrium-aluminum-garnet laser compared with control.

Single-stage interpolation flaps in facial reconstruction.

BACKGROUND: Relatively deep and complex surgical defects, particularly when adjacent to or involving free margins, present significant reconstructive challenges. When the use of local flaps is precluded by native anatomic restrictions, interpolation flaps may be modified to address these difficult wounds in a single operative session. OBJECTIVE: To provide a framework to approach difficult soft tissue defects arising near or involving free margins and to demonstrate appropriate design and execution of single-stage interpolation flaps for reconstruction of these wounds. METHODS: Examination of our utilization of these flaps based on an anatomic region and surgical approach. RESULTS: A region-based demonstration of flap conceptualization, design, and execution is provided. CONCLUSION: Tunneled, transposed, and deepithelialized variations of single-stage interpolation flaps provide versatile options for reconstruction of a variety of defects encroaching on or involving free margins. The inherently robust vascularity of these flaps supports importation of necessary tissue bulk while allowing aggressive contouring to restore an intricate native topography. Critical flap design allows access to distant tissue reservoirs and placement of favorable incision lines while preserving the inherent advantages of a single operative procedure.

Reconsidering the diagnostic and prognostic utility of LN-2 for undifferentiated pleomorphic sarcoma and atypical fibroxanthoma.

The topic of distinguishing atypical fibroxanthoma (AFX) from undifferentiated pleomorphic sarcoma (UPS), formerly malignant fibrous histiocytoma, is highly controversial. Although their clinical behavior is disparate, AFX and UPS commonly appear nearly identical on routine histopathologic examination. Although conceptually useful, subcategorization of UPS into superficial (confined to the dermis and subcutaneous tissue) and deep (involvement of fascia and deeper structures) types has not improved our ability to differentiate UPS from AFX. Numerous authors have purported LN-2 (CD74) immunopositivity as able to distinguish UPS from AFX and to predict those rare AFX likely to behave aggressively, although only a single prior study has been dedicated to evaluating this marker. We performed LN-2 staining of 14 AFX, 8 superficial UPS, and 65 deep UPS specimens using an identical protocol as described by prior authors. Of the 73 total UPS specimens, only 1 (1.4%) stained strongly with LN-2, as compared with 3 of 14 (21%) AFX (P = 0.012). One of 2 (50%) clinically aggressive AFX tumors that later exhibited both local recurrence and metastasis stained strongly for LN-2, whereas 2 of 12 (17%) of the more indolent tumors stained strongly with this marker (P = 0.40). Our data do not replicate prior reports of LN-2 as a sensitive and specific marker for UPS, or as indicative of prognosis for AFX, and therefore does not support the use of LN-2 as either a diagnostic or prognostic marker.

Multiple eruptive pilomatricomas in a 9-year-old boy with glioblastoma.

A 9-year-old male presented to our dermatology clinic with a recent history of developing numerous cutaneous pilomatricomas, and was subsequently discovered to have sustained a recurrence of his glioblastoma multiforme. Immunohistochemical staining of a representative pilomatricoma and his original brain tumor revealed upregulation and nuclear localization of beta-catenin, a sign associated with poor prognosis in glioblastoma. We hypothesize that the development of multiple pilomatricomas may have been a hallmark of this patient's tumor recurrence and provide support for a recent report of an association between multiple pilomatricomas and gliomatosis cerebri.

Malignant fibrous histiocytoma: changing perceptions and management challenges.

Malignant fibrous histiocytoma (MFH) is a rare neoplasm exhibiting a propensity for aggressive clinical behavior. This review seeks to provide the practicing dermatologist with a contemporary understanding of MFH in order to guide management decisions. An extensive review of the literature was conducted using PubMed and OVID databases, searching for articles regarding MFH and undifferentiated pleomorphic sarcoma. The modern conception of MFH has changed extensively from clinical and pathologic standpoints. Limitations of the study included the reliability of past studies given the changing nature of MFH as a diagnostic entity. MFH represents an aggressive neoplasm with unique molecular, immunohistochemical, and behavioral characteristics. Practicing clinicians would benefit from a contemporary understanding of these tumors, particularly as a discussion of advances in the conception of MFH is largely absent in the dermatologic literature.

Spindle cell neoplasms encountered in dermatologic surgery: a review.

Cutaneous spindle cell tumors share the common feature of appearing as spindle-shaped cells on light microscopy. Their pathogenesis, presentation, and prognosis are highly variable, and numerous techniques for workup and treatment have been reported. We performed an analysis of the available scientific literature in order to codify the clinical, immunohistochemical, and biologic features of these tumors and to provide insight into the most effective practices for their management, with a focus on Mohs micrographic surgery (MMS). In this article, the clinical and histopathological characteristics of dermatofibrosarcoma protuberans, atypical fibroxanthoma, malignant fibrous histiocytoma, spindle cell squamous cell carcinoma, superficial leiomyosarcoma, desmoplastic melanoma, cutaneous angiosarcoma, and myofibrosarcoma are described, and methods for diagnosis, workup, treatment, and surveillance are evaluated. Cutaneous spindle cell neoplasms are diverse in origin, presentation, and behavior. Immunostaining assists in differentiating among the various types. Further workup is sometimes indicated to characterize local invasion or assess for metastatic disease. Surgery is typically the first-line treatment, and MMS is associated with low recurrence rates and a tissue-sparing advantage for many tumors. Adjuvant treatments, including radiation therapy, molecular-targeted therapy, and conventional chemotherapy, are sometimes indicated, and close clinical surveillance is required after treatment.

The evolving conception and management challenges of malignant fibrous histiocytoma.

BACKGROUND: Malignant fibrous histiocytoma (MFH) is a rare and aggressive tumor. Mohs micrographic surgery (MMS) has been reported as an effective treatment, although most cases were published before advances in cytopathologic techniques led to reclassification of many tumors. OBJECTIVE: To evaluate a contemporary cohort of individuals with MFH and analyze management practices. METHODS: We reviewed all cases of MFH diagnosed at our institution from January 1995 to December 2010, evaluating 839 records to identify 36 patients undergoing management of tumors of the head and neck. RESULTS: Seventeen of the total 36 patients (47%; mean age 67) experienced tumor recurrence, and 10 (28%) developed metastases. Seven of nine patients initially treated with MMS (78%), and 10 of 24 (42%) treated with WLE experienced recurrence (p = .06). Patients treated with MMS had smaller tissue defects after surgery. The mean contemporary recurrence rate of MFH treated with MMS is significantly higher (58.8%) than the cumulative recurrence rate reported before 2000 (7.4%) (p < .001). CONCLUSIONS: Our study is consistent with reports of MFH as an aggressive neoplasm and describes the largest population treated with MMS in 3 decades. The changing conception of MFH, along with a propensity for in-transit metastases, may explain higher contemporary recurrence rates.