Publications by authors named "Roberto Novoa"

61 Publications

Next generation sequencing confirms T-cell clonality in a subset of pediatric pityriasis lichenoides.

J Cutan Pathol 2021 Oct 6. Epub 2021 Oct 6.

Departments of Dermatology, Stanford University Medical Center, Stanford, CA.

Background: Pityriasis lichenoides (PL) is a papulosquamous disease that affects both adults and children. Previous studies have shown a subset of this entity to have clonal T-cell populations via PCR based assays. In this study, we sought to implement next generation sequencing as a more sensitive and specific test to examine for T-cell clonality within the pediatric population.

Methods: We identified 18 biopsy specimens from 12 pediatric patients with clinical and histopathologic findings compatible with PL. Patient demographics, clinical features, management, and histopathologic findings were reviewed. All specimens were analyzed for clonality with next generation sequencing of T-cell receptor beta (TRB) and gamma (TRG) genes.

Results: Of the 12 patients, 9 (75%) had complete resolution of lesions at the time of data collection (mean follow up 31 months). The remaining three patients significantly improved with methotrexate (with or without acitretin). Interestingly, 7 of 12 patients (58%) and 9 of 17 biopsy specimens (53%) showed evidence of T-cell clonality. Two patients showed matching TRB clones from different anatomic sites.

Conclusions: T-cell clonality is a common finding in PL, likely representing a "reactive clonality" rather than a true lymphoproliferative disorder. Clonality alone cannot be used as a means to distinguish PL from lymphomatoid papulosis or cutaneous lymphoma. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/cup.14143DOI Listing
October 2021

Appropriate Use Criteria (AUC) for Ancillary Diagnostic Testing in Dermatopathology: New Recommendations for 11 tests and 220 clinical scenarios from the American Society of Dermatopathology AUC Committee.

J Cutan Pathol 2021 Sep 18. Epub 2021 Sep 18.

Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: Appropriate use criteria (AUC) provide patient-centered physician guidance in test selection. An initial set of AUC were reported by the American Society of Dermatopathology (ASDP) in 2018. AUC reflect evidence collected at single timepoints and may be affected by evolving evidence and experience.

Objective: Update and expand AUC for selected tests.

Methods: RAND/UCLA methodology used includes: 1) Literature review; 2) Review of previously-rated tests and previously-employed clinical scenarios; 3) Selection of previously-rated tests for new ratings; 4) Development of new clinical scenarios; 5) Selection of additional tests; 6) Three rating rounds with feedback and group discussion after rounds 1 and 2.

Results: For 220 clinical scenarios comprising lymphoproliferative (light chain clonality), melanocytic (CGH, FISH, RT-PCR, TERT promoter), vascular disorders (MYC), and inflammatory dermatoses (PAS, GMS) consensus by panel raters was reached in 172/220 (78%) scenarios, with 103/148 (70%) rated "usually appropriate" or "rarely appropriate" and 45/148 (30%), "appropriateness uncertain."

Limitations: The study design only measures appropriateness. Cost, availability, test comparison, and additional clinical considerations are not measured. The possibility that the findings of this study may be influenced by the inherent biases of the dermatopathologists involved in the study cannot be excluded.

Conclusions: AUC are reported for selected diagnostic tests in clinical scenarios that occur in dermatopathology practice. Adhering to AUC may reduce inappropriate test utilization and improve health care delivery. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/cup.14135DOI Listing
September 2021

Immunohistochemical ALK Expression in Granular Cell Atypical Fibroxanthoma: A Diagnostic Pitfall for ALK-Rearranged Non-neural Granular Cell Tumor.

Am J Dermatopathol 2021 Nov;43(11):831-834

Department of Pathology, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA.

Abstract: Atypical fibroxanthoma (AFX) is a neoplasm that most commonly occurs on sun-damaged skin of the head and neck in elderly patients and that usually exhibits indolent clinical behavior with complete excision. The granular cell variant of AFX demonstrates overlapping histopathologic features with dermal non-neural granular cell tumor (NNGCT), which typically arises on the extremities of young to middle aged adults with rare reports of regional metastasis. A subset of NNGCT harbors ALK rearrangements and expresses ALK by immunohistochemistry. Here, we present 2 cases of granular cell AFX occurring on the scalp of males aged 73 and 87 with ALK expression by immunohistochemistry and no evidence of an ALK rearrangement on fluorescence in situ hybridization, representing a diagnostic pitfall for NNGCT.
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http://dx.doi.org/10.1097/DAD.0000000000001931DOI Listing
November 2021

TrueImage: A Machine Learning Algorithm to Improve the Quality of Telehealth Photos.

Pac Symp Biocomput 2021 ;26:220-231

Department of Electrical Engineering, Stanford University, Stanford, CA 94305, USA† Correspondence authors*These authors contributed equally,

Telehealth is an increasingly critical component of the health care ecosystem, especially due to the COVID-19 pandemic. Rapid adoption of telehealth has exposed limitations in the existing infrastructure. In this paper, we study and highlight photo quality as a major challenge in the telehealth workflow. We focus on teledermatology, where photo quality is particularly important; the framework proposed here can be generalized to other health domains. For telemedicine, dermatologists request that patients submit images of their lesions for assessment. However, these images are often of insufficient quality to make a clinical diagnosis since patients do not have experience taking clinical photos. A clinician has to manually triage poor quality images and request new images to be submitted, leading to wasted time for both the clinician and the patient. We propose an automated image assessment machine learning pipeline, TrueImage, to detect poor quality dermatology photos and to guide patients in taking better photos. Our experiments indicate that TrueImage can reject ~50% of the sub-par quality images, while retaining ~80% of good quality images patients send in, despite heterogeneity and limitations in the training data. These promising results suggest that our solution is feasible and can improve the quality of teledermatology care.
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March 2021

Cutaneous acral myofibroma with PDGFRB mutation in a patient with linear morphea en coup de sabre.

J Cutan Pathol 2021 Aug 11;48(8):1097-1100. Epub 2021 Feb 11.

Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.

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http://dx.doi.org/10.1111/cup.13971DOI Listing
August 2021

Concurrent Trypanosoma cruzi and Cytomegalovirus Reactivation in an Immunosuppressed Patient With Limited Cutaneous Systemic Sclerosis.

Am J Dermatopathol 2020 Nov 16. Epub 2020 Nov 16.

Department of Dermatology, Stanford University School of Medicine, Redwood City, CA.

Chagas disease, a multisystem infection caused by the protozoan Trypanosoma cruzi, is primarily found in Latin America. In recent years, prevalence has increased in the United States, where reactivation is the most common clinical scenario. Here, we describe cutaneous reactivation of T. cruzi in a patient with limited cutaneous systemic sclerosis on immunosuppression therapy who simultaneously presented with cytomegalovirus reactivation. Histopathology showed parasitized histiocytes in the superficial and deep dermis. Occasional epidermal keratinocytes were also parasitized, and rare organisms were also seen in the walls of blood vessels. Also noted were viral cytopathic changes within the vascular endothelium, and immunostaining confirmed cytomegalovirus. In this report, we describe the difference in cutaneous findings between reactivated and acute Chagas disease, and we also review the histopathologic features that help distinguish T.cruzi from other intracellular organisms.
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http://dx.doi.org/10.1097/DAD.0000000000001842DOI Listing
November 2020

ALK-positive compound Spitz nevus with extensive perineural and intraneural neurotropism.

J Cutan Pathol 2021 Jan 8;48(1):154-159. Epub 2020 Nov 8.

Department of Pathology, Stanford Medicine, Stanford, California, USA.

Historically recognized by their characteristic histopathologic features, Spitz neoplasms are now known to be molecularly defined by mutually exclusive recurrent abnormalities that cause activation of the MAPK pathway. Spitz neoplasms with ALK rearrangements frequently demonstrate polypoid growth with a plexiform arrangement of nested, fusiform melanocytes in intersecting fascicles. Although neurotropism has been described in indolent Spitz neoplasms, this feature is not frequently mentioned in publications on histopathologic assessment of this group of melanocytic tumors. Here, we present an unusual case of a 3-year-old female with an ALK-positive compound Spitz nevus with extensive perineural and intraneural neurotropism occurring on the vermilion border of the lower lip.
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http://dx.doi.org/10.1111/cup.13890DOI Listing
January 2021

Cutaneous T-cell lymphomas with pathogenic somatic mutations and absence of detectable clonal T-cell receptor gene rearrangement: two case reports.

Diagn Pathol 2020 Sep 28;15(1):122. Epub 2020 Sep 28.

Department of Pathology, Stanford Medicine, Stanford, CA, 94305, USA.

Background: Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of extranodal non-Hodgkin lymphomas for which diagnosis can be challenging given the potential for overlap with inflammatory dermatoses. Current diagnostic criteria for CTCL incorporate clinical and histopathologic findings as well as results of T-cell receptor (TCR) gene sequencing. Molecular interrogation of TCR genes, TRG and TRB, has proven to be a critical tool for confirming diagnoses of CTCL and for disease tracking after initiation of therapy or after stem cell transplant. Methods for confirming a diagnosis of lymphoma in the absence of TCR gene clonality are lacking. We present two patients with CTCL with pathogenic somatic mutations in the absence of TRG and TRB clonality.

Case Presentations: Case 1: A 38-year-old male had a 19-year history of a diffuse skin rash with papulosquamous, granulomatous, and verrucous features and progressive ulcerated plaques and tumors demonstrating an atypical CD4+ T-cell infiltrate with expression of cytotoxic markers CD56, TIA-1, granzyme, and perforin on histopathology. No definitive evidence for T-cell clonality was detected by conventional PCR of 6 biopsies or by next-generation sequencing (NGS) of 14 biopsies. Somatic mutational profiling of a skin biopsy revealed pathogenic mutations in PIKC3D and TERT promoter hotspots, confirming the presence of a clonal process. Case 2: A 69-year-old male with a 13-year history of progressive, diffuse hypertrophic and eroded plaques showed an atypical CD4+ T-cell infiltrate with subset expression of TIA-1 and granzyme on histopathology. No TCR clonality was detected by TCR-NGS of 6 biopsies. Somatic mutational profiling of a skin biopsy detected a pathogenic mutation in TP53, confirming the presence of a clonal process.

Conclusions: These cases highlight how detection of pathogenic somatic mutations can confirm a diagnosis of lymphoma in a clinically and histopathologically suspicious cutaneous lymphoid proliferation without detectable TCR clonality.
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http://dx.doi.org/10.1186/s13000-020-01022-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523289PMC
September 2020

Histopathologic Characterization of Mogamulizumab-associated Rash.

Am J Surg Pathol 2020 12;44(12):1666-1676

Department of Dermatology, Stanford University School of Medicine, Redwood City.

Rash is one of the most common adverse events observed with mogamulizumab, an anti-C-C chemokine receptor 4 monoclonal antibody approved for previously treated mycosis fungoides (MF) and Sezary syndrome (SS). Given the nonspecific clinical presentations of this rash, histopathologic distinction from MF/SS is critical for informing clinical management. We performed a comprehensive characterization of the histopathologic findings in mogamulizumab-associated rash (MAR) with the integration of high-throughput sequencing of T-cell receptor (TCR) genes. Fifty-two biopsy specimens from 19 patients were evaluated retrospectively. Three major histologic reaction patterns were identified: spongiotic/psoriasiform dermatitis (33/52), interface dermatitis (11/52), and granulomatous dermatitis (8/52). Almost half of the specimens (21/52) showed at least 2 of these reaction patterns concurrently. Dermal eosinophils were not a consistent feature, being present in only half (27/52) of specimens and prominent in only 3. Features mimicking MF/SS, including lymphocyte exocytosis, lamellar fibroplasia, and adnexal involvement, were commonly seen but tended to be focal and mild. In 38/43 specimens with available immunohistochemistry, intraepidermal lymphocytes demonstrated a CD4:CD8 ratio ≤1 : 1. Low background levels of the patient's previously identified MF/SS-associated TCR sequence(s) were demonstrated in 20/46 specimens analyzed by high-throughput sequencing of TCR. We conclude that MAR may demonstrate diverse histologic features. Findings that may distinguish MAR from MF/SS include the inverted or normalized CD4:CD8 ratio within intraepidermal lymphocytes and demonstration of absent or nondominant levels of disease-associated TCR sequences. Correlation with the clinical findings and immunohistochemical and molecular characterization of the patient's MF/SS before mogamulizumab, when possible, may facilitate recognition of MAR.
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http://dx.doi.org/10.1097/PAS.0000000000001587DOI Listing
December 2020

Imatinib as a potentially effective therapeutic alternative in corticosteroid-resistant eosinophilic fasciitis.

Pediatr Dermatol 2020 Nov 24;37(6):1171-1172. Epub 2020 Sep 24.

Department of Dermatology, Stanford University, Palo Alto, California, USA.

Eosinophilic fasciitis (EF) is a rare condition in children that is typically treated with systemic corticosteroids. We present the case of a 9-year-old boy with biopsy-proven EF, refractory to systemic corticosteroids and methotrexate. The tyrosine kinase inhibitor imatinib was added as adjuvant therapy, leading to improvement in joint function and skin laxity. Our case is the first to suggest the anti-fibrotic properties of imatinib may benefit EF patients.
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http://dx.doi.org/10.1111/pde.14327DOI Listing
November 2020

PRAME expression in melanocytic proliferations with intermediate histopathologic or spitzoid features.

J Cutan Pathol 2020 Dec 10;47(12):1123-1131. Epub 2020 Sep 10.

Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.

Background: PRAME (PReferentially expressed Antigen in MElanoma) has shown utility in distinguishing melanoma from benign melanocytic lesions, but knowledge of its expression pattern in intermediate melanocytic and spitzoid proliferations is limited.

Methods: Immunohistochemical expression of PRAME was examined in 112 melanocytic proliferations with intermediate histopathologic or spitzoid features.

Results: Any intensity of nuclear PRAME staining in at least 60% of lesional melanocytes was determined as the best threshold for diffuse staining in this cohort. Nearly all non-spitzoid melanomas (23/24; 95.8%) demonstrated diffuse PRAME expression. PRAME was completely negative in 95.6% (43/45) of mitotically-active nevi, traumatized nevi, nevi with persistent/recurrent features, and dysplastic nevi. Most Spitz nevi (15/20) and atypical Spitz tumors (10/13) entirely lacked PRAME expression. One Spitz nevus, one atypical Spitz tumor, and one spitzoid melanoma (1/2) demonstrated diffuse PRAME expression.

Conclusions: Although diffuse PRAME expression is generally limited to malignant melanoma, benign Spitz nevi and atypical Spitz tumors can infrequently express diffuse PRAME. PRAME immunohistochemistry can be useful in the evaluation of atypical melanocytic proliferations with intermediate histopathologic features but should be interpreted with caution in the setting of spitzoid neoplasms.
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http://dx.doi.org/10.1111/cup.13818DOI Listing
December 2020

Diffuse PRAME expression is highly specific for malignant melanoma in the distinction from clear cell sarcoma.

J Cutan Pathol 2020 Dec 10;47(12):1226-1228. Epub 2020 Sep 10.

Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.

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http://dx.doi.org/10.1111/cup.13812DOI Listing
December 2020

Differentiation syndrome during ivosidenib treatment with immunohistochemistry showing isocitrate dehydrogenase R132H mutation.

J Cutan Pathol 2020 Nov 28;47(11):1042-1045. Epub 2020 Aug 28.

Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.

We report a case of differentiation syndrome in a patient receiving the IDH1 inhibitor ivosidenib, with skin biopsy showing isocitrate dehydrogenase (IDH) R132H-mutated leukemia cutis. A 72-year-old man with IDH1-mutated acute myeloid leukemia (AML), status-post allogeneic cell transplantation, on ivosidenib for 6 months, was admitted for culture-negative neutropenic fever, pink and purpuric plaques and patches on the legs, abdomen and back, edema, hypotension, and shortness of breath. Skin biopsy revealed an infiltrate of atypical, immature, myeloperoxidase-positive mononuclear cells compatible with leukemia cutis or Sweet syndrome. Although dermal edema and interstitial neutrophilic infiltrate with karyorrhexis characteristic of Sweet syndrome were not seen, the atypical cells lacked expression of CD117 and CD34, which were expressed in the original leukemia. Additional immunohistochemical staining of suspected blasts was strongly positive for IDH1 R132H, suggesting a diagnosis of leukemia cutis. As the immunophenotype of blasts in skin infiltrates can significantly differ from the immunophenotype seen in blood and bone marrow, this case shows that mutation-specific antibodies such as anti-IDH1 R132H may be useful to help distinguish malignant from non-malignant infiltrates in the skin. Furthermore, differentiation syndrome may show histopathologic features of leukemia cutis on skin biopsy.
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http://dx.doi.org/10.1111/cup.13780DOI Listing
November 2020

Simultaneous coccidioidomycosis and phaeohyphomycosis in a kidney transplant recipient: A case report and literature review.

Transpl Infect Dis 2020 Dec 25;22(6):e13365. Epub 2020 Jun 25.

Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Advances in solid organ transplantation have improved the survival of end-stage organ disease at the expense of an increased risk for opportunistic infections. Unusual clinical presentations and the possibility of concurrent infections make diagnosing invasive fungal infection (IFI) more difficult. Here, we present a case of simultaneous vertebral infection caused by Coccidioides immitis-posadasii and subcutaneous phaeohyphomycosis due to Nigrograna mackinnonii in a kidney transplant recipient. The diagnosis of both infections required invasive procedures to obtain tissue and a high index of suspicion that more than one IFI could be present. A multidisciplinary team approach for the management of immunocompromised patients with suspected or diagnosed IFI is warranted.
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http://dx.doi.org/10.1111/tid.13365DOI Listing
December 2020

Diagnostic Utility of LEF1 Immunohistochemistry in Differentiating Deep Penetrating Nevi From Histologic Mimics.

Am J Surg Pathol 2020 10;44(10):1413-1418

Departments of Pathology.

Deep penetrating nevi (DPNs) are intermediate grade lesions which have the capacity to recur, metastasize, or progress to melanoma. Differentiating DPN from other melanocytic lesions including blue and cellular blue nevi can be diagnostically challenging, and markers to distinguish these entities can be useful. Mutations of the β-catenin and mitogen-activated protein kinase pathways have recently been elucidated as distinctive of DPN. This pathway can subsequently activate lymphoid enhancer-binding factor 1 (LEF1), a transcription factor shown to facilitate the epithelial-mesenchymal transition to propagate tumorigenesis. Seventy-two cases in total were examined on hematoxylin and eosin sections and with β-catenin and LEF1 immunohistochemistry. This included: DPN (14), cellular blue nevi (19), blue nevi (15), congenital melanocytic nevi (12), and melanoma (12). Nuclear expression of LEF1, present throughout the entire depth of the lesion, was noted in 13/14 (93%) of DPN, 0/19 (0%) of cellular blue nevi, 0/15 (0%) of blue nevi, 1/12 (8%) of congenital melanocytic nevi, and 9/12 (75%) of melanoma cases. Nuclear expression of β-catenin, present throughout the entire depth of the lesion, was noted in 14/14 (100%) of DPN, 0/18 (0%) of cellular blue nevi, 0/15 (0%) of blue nevi, 1/12 (8%) of congenital melanocytic nevi, and 1/12 (8%) of melanoma cases. A majority of congenital melanocytic nevi demonstrated a gradient of LEF1 and β-catenin expression with more intense staining superficially and loss of staining with increasing depth. Deep, uniform nuclear LEF1 combined with β-catenin immunohistochemical staining can be useful in distinguishing DPN from histologic mimics.
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http://dx.doi.org/10.1097/PAS.0000000000001513DOI Listing
October 2020

Shoshin beriberi in a patient with oral and cutaneous graft-versus-host disease.

JAAD Case Rep 2020 May 29;6(5):420-421. Epub 2020 Apr 29.

Department of Dermatology, Stanford University School of Medicine, Stanford, California.

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http://dx.doi.org/10.1016/j.jdcr.2020.02.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200185PMC
May 2020

Reticulohistiocytoma (solitary epithelioid histiocytoma) with mutations in RAF1 and TSC2.

J Cutan Pathol 2020 Oct 20;47(10):985-987. Epub 2020 Jul 20.

Department of Pathology, Stanford University Medical Center, Stanford, California, USA.

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http://dx.doi.org/10.1111/cup.13727DOI Listing
October 2020

TERT and TERT promoter in melanocytic neoplasms: Current concepts in pathogenesis, diagnosis, and prognosis.

J Cutan Pathol 2020 Aug 3;47(8):710-719. Epub 2020 Apr 3.

Laboratorio Recavarren Emanuel, Clínica Ricardo Palma, Lima, Peru.

Background And Objective: Located on chromosome locus 5p15.33, telomerase reverse transcriptase (TERT or hTERT) encodes the catalytic subunit of telomerase which permits lengthening and preservation of telomeres following mitosis. Mutations in TERT promoter (TERT-p) upregulate expression of TERT, allowing survival of malignant cells and tumor progression in wide variety of malignancies including melanoma. The objective of this review is to examine the roles of TERT and TERT-p in the pathogenesis, diagnosis, and prognostication of cutaneous melanoma.

Methods: All studies of TERT or TERT-p in cutaneous melanocytic neoplasms with the following inclusion criteria were reviewed: publication date between 2010 and 2019, English language, and series of ≥3 cases were reviewed for evidence supporting the role of TERT in pathogenesis, diagnosis, and prognosis. Studies with <3 cases or focused primarily on mucosal or uveal melanocytic tumors were excluded.

Results And Conclusion: TERT-p mutations are frequent in chronic and non-chronic sun damage melanoma and correlate with adverse prognosis, inform pathogenesis, and may provide diagnostic support. While TERT-p mutations are uncommon in acral melanoma, TERT copy number gains and gene amplification predict reduced survival. Among atypical spitzoid neoplasms, TERT-p mutations identify biologically aggressive tumors and support the diagnosis of spitzoid melanoma. TERT-p methylation may have prognostic value in pediatric conventional melanoma and drive tumorigenesis in melanoma arising within congenital nevi. Finally, TERT-p mutations may aid in the differentiation of recurrent nevi from recurrent melanoma.
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http://dx.doi.org/10.1111/cup.13691DOI Listing
August 2020

Cutaneous pleomorphic fibromas arising in patients with germline TP53 mutations.

J Cutan Pathol 2020 Aug 6;47(8):734-741. Epub 2020 Apr 6.

Department of Pathology, Stanford University School of Medicine, Stanford, California.

Pleomorphic fibromas are rare benign cutaneous neoplasms associated with deletion/loss of chromosomes 13q and 17p, where RB1 and TP53 are located, respectively. Herein, we report five cases of pleomorphic fibroma arising in patients with germline TP53 mutations, suggesting a potential link with Li-Fraumeni syndrome. All three patients were female and young (mean age 27) with a strong personal and/or family oncologic history and confirmed pathogenic germline TP53 mutations. In two patients, multiple pleomorphic fibromas were diagnosed. Clinically, the lesions arose at various cutaneous sites and were small (≤2 cm) and raised (4/5). Histopathologically, the tumors were paucicellular, composed of atypical spindled to stellate cells with hyperchromatic and variably pleomorphic nuclei. Mitotic activity was exceedingly low, although rare atypical mitotic figures were seen in one case. Immunohistochemically, the tumor cells were diffusely positive for p16 (3/3) and showed loss of Rb expression (5/5). All cases showed aberrant p53 expression (overexpression in 4, complete loss in 1). The tumors have followed a benign clinical course with no evidence of progression or recurrence. In conclusion, the development of multiple pleomorphic fibromas in a young patient may be a clue to an underlying genetic cancer syndrome involving TP53.
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http://dx.doi.org/10.1111/cup.13686DOI Listing
August 2020

Disseminated tuberculosis presenting as medium-vessel vasculitis in an immunocompromised host.

J Cutan Pathol 2020 Aug 19;47(8):725-728. Epub 2020 Mar 19.

Department of Dermatology, Stanford University Medical Center, Stanford, California, USA.

Cutaneous tuberculosis is an uncommon entity with several clinical forms recognized. Histopathologically, most cases are characterized by granulomatous inflammation and caseating necrosis, although less common findings, including vasculitis, have also been described. We report a 55-year-old male with a history of recently diagnosed dermatomyositis receiving immunosuppression with mycophenolate mofetil and prednisone, who developed multifocal soft tissue abscesses and an indurated erythematous plaque on the back. Skin biopsy of the back revealed a necrotizing medium-vessel vasculitis. Mycobacterium tuberculosis was detected in the skin via acid-fast bacilli stain and confirmed by tissue culture and polymerase chain reaction. Cutaneous findings improved rapidly with antituberculosis therapy. This case illustrates an uncommon clinical and histopathologic presentation of disseminated tuberculosis.
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http://dx.doi.org/10.1111/cup.13678DOI Listing
August 2020

Comparison of C3d immunohistochemical staining to enzyme-linked immunosorbent assay and immunofluorescence for diagnosis of bullous pemphigoid.

J Am Acad Dermatol 2020 Jul 14;83(1):172-178. Epub 2020 Feb 14.

Department of Dermatology, the University of Pennsylvania, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

Background: Bullous pemphigoid (BP), the most common autoimmune blistering disease, may be diagnostically challenging. Direct immunofluorescence (DIF), indirect immunofluorescence (IIF), enzyme-linked immunosorbent assay (ELISA), and recently, C3d immunohistochemistry (IHC), are used as adjuncts to diagnosis.

Objective: To compare C3d IHC to DIF, IIF, and ELISA testing in BP diagnosis.

Methods: C3d IHC was performed on skin biopsy specimens from 51 patients (27 with BP and 24 with other blistering diseases) and compared to DIF and IIF, with anti-BP180 or anti-BP230 ELISA results used as the gold standard.

Results: We found C3d IHC, DIF, and IIF had similar sensitivity (74.1%, 63.1%, and 70.4%), specificity (95.8%, 100%, and 100%), positive predictive value (95.2%, 100%, and 100%), and negative predictive value (76.7%, 70.6%, and 75%) for BP. Cases with positive C3d IHC, DIF, and IIF had significantly higher anti-BP180 and anti-BP230 by ELISA than cases with negative testing (P < .0001). False-negative IIF results were associated with lower BP230 compared with true-positive results (P = .03).

Limitations: This was a single-center, retrospective study.

Conclusion: Our study compared C3d IHC to DIF and IIF in BP diagnosis, demonstrating C3d IHC on fixed tissue provides similar diagnostic utility to immunofluorescence and ELISA.
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http://dx.doi.org/10.1016/j.jaad.2020.02.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480887PMC
July 2020

Validation of Image Quality and Diagnostic Accuracy Using a Mobile Phone Camera Microscope Adaptor Compared With Glass Slide Review in Teledermatopathology.

Am J Dermatopathol 2020 May;42(5):349-353

Department of Dermatology, University of Pennsylvania, Philadelphia, PA.

New modalities of evaluating histopathology, such as whole-slide imaging, have been validated in the field of dermatopathology but are often unfeasible and unavailable in developing countries. Widely available across the globe, mobile phone camera technology represents a potential simple and inexpensive method of imaging histologic slides through the use of a mobile phone camera microscope adaptor. This study aims to validate the use of a commercially available adaptor in the diagnosis of inflammatory and infectious conditions in dermatopathology. Representative images were taken of slides for fifty-four cases using the adaptor and shared through a cloud-based platform with five dermatopathologists who rendered diagnoses and judged the quality of the images. After a washout period of 8 weeks, the same cases were assessed by the same dermatopathologists using the original glass slides. The intraobserver concordance rate was 93.3%, and the quality of the mobile phone images was rated as "excellent" or "diagnostic" in 94.4% of the cases. This study validates the use of this low-tech and low-cost adaptor as a reliable tool in teledermatopathology. Limitations of the study include those inherent to use of the adaptor and the limited panel of diagnoses. The primary value of this device may be in developing countries, but its practicality and ease of use lend itself to use in academic and consultative settings in the developed world as well.
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http://dx.doi.org/10.1097/DAD.0000000000001529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160027PMC
May 2020

Marking the Path Toward Artificial Intelligence-Based Image Classification in Dermatology.

JAMA Dermatol 2019 Oct;155(10):1105-1106

Department of Dermatology, Stanford University School of Medicine, Stanford, California.

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http://dx.doi.org/10.1001/jamadermatol.2019.1633DOI Listing
October 2019

Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma: Updates on Classification and Management.

Dermatol Clin 2019 Jul 16;37(3):253-259. Epub 2019 Apr 16.

Department of Dermatology, Stanford University School of Medicine, 450 Broadway Street, Pavilion C, 2nd Floor-MC5334, Redwood City, CA 94063, USA.

Atypical fibroxanthoma and undifferentiated pleomorphic sarcoma, or pleomorphic dermal sarcoma, are rare malignant cutaneous neoplasms existing along a clinicopathologic spectrum. Although these tumors share many similarities, recognition of distinguishing characteristics may predict differences in clinical behavior and outcomes. Salient features defining atypical fibroxanthoma include superficial tumors with minimal high-risk histologic features. Deeper tumors with high-risk histologic features are often clinically aggressive and should be appropriately designated as pleomorphic dermal sarcoma. Surgery remains gold standard in management; tumor extirpation with complete margin control is critical. In the high-risk tumor cohort, comprehensive evaluation and multidisciplinary management is paramount for optimal outcomes.
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http://dx.doi.org/10.1016/j.det.2019.02.001DOI Listing
July 2019

Artificial intelligence and dermatology: opportunities, challenges, and future directions.

Semin Cutan Med Surg 2019 Mar 1;38(1):E31-37. Epub 2019 Mar 1.

Department of Dermatology, Stanford University, Stanford, California.

The application of artificial intelligence (AI) to medicine has considerable potential within dermatology, where the majority of diagnoses are based on visual pattern recognition. Opportunities for AI in dermatology include the potential to automate repetitive tasks; optimize time-consuming tasks; extend limited medical resources; improve interobserver reliability issues; and expand the diagnostic toolbox of dermatologists. To achieve the full potential of AI, however, developers must aim to create algorithms representing diverse patient populations; ensure algorithm output is ultimately interpretable; validate algorithm performance prospectively; preserve human-patient interaction when necessary; and demonstrate validity in the eyes of regulatory bodies.
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http://dx.doi.org/10.12788/j.sder.2019.DOI Listing
March 2019

Introduction, Dermatology, Data, and Informatics.

Semin Cutan Med Surg 2019 Mar 1;38(1):E1-E8. Epub 2019 Mar 1.

Department of Dermatology, Stanford University, Stanford, California.

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http://dx.doi.org/10.12788/j.sder.2019.012DOI Listing
March 2019

Biomarker discovery analysis: Alterations in p14, p16, p53, and BAP1 expression in nevi, cutaneous melanoma, and metastatic melanoma.

Pigment Cell Melanoma Res 2019 05 10;32(3):474-478. Epub 2019 Feb 10.

Department of Pathology, Stanford University Medical Center, Stanford, California.

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http://dx.doi.org/10.1111/pcmr.12768DOI Listing
May 2019
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