Publications by authors named "Ata S Moshiri"

16 Publications

  • Page 1 of 1

A case of endocrine mucin-producing sweat gland carcinoma with distant metastasis.

J Cutan Pathol 2021 Mar 3. Epub 2021 Mar 3.

Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare cutaneous adnexal neoplasm typically arising on the face of older individuals, most commonly around the eyelids. Histopathologic features include a circumscribed proliferation of low-grade epithelioid cells with areas of cystic and cribriform growth, foci of intracytoplasmic and extracellular mucin, and coexpression of endocrine, neuroendocrine, and cytokeratin markers by immunohistochemistry. Given histopathologic and immunohistochemical similarities, EMPSGC is often likened to solid papillary carcinoma of the breast and endocrine ductal carcinoma in situ, and is thought by many to represent a forme fruste of mucinous carcinoma of the skin. To date, the vast majority of reported cases of EMPSGC have been described as having indolent behavior, with no cases of distant metastasis yet reported. Here we report a unique case of EMPSGC that recurred over several years following standard surgical excision and Mohs micrographic surgery, with subsequent metastasis to the parotid gland and axial skeleton.
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http://dx.doi.org/10.1111/cup.13999DOI Listing
March 2021

Involving Patients in Their Own Health Care Choices-Altruism Begets Altruism.

JAMA Netw Open 2021 02 1;4(2):e210152. Epub 2021 Feb 1.

Division of Dermatology, Department of Medicine, University of Washington, Seattle.

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http://dx.doi.org/10.1001/jamanetworkopen.2021.0152DOI Listing
February 2021

Metastatic Melanoma With Features of Desmoplastic Melanoma in a Patient With Primary Cutaneous Superficial Spreading Melanoma With Epithelioid Features.

Am J Dermatopathol 2021 Jan 12. Epub 2021 Jan 12.

Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; Division of Dermatology and Department of Pathology, University of Washington, Seattle, WA; Department of Pathology, Bryn Mawr Hospital, Bryn Mawr, PA; and Department of Surgery, Hospital of University of Pennsylvania, Philadelphia, PA.

Abstract: The synchronous incidence of 2 different subtypes of melanoma is very rare. Desmoplastic melanoma (DM) can be a diagnostic challenge because of its frequent appearance as a dermal banal spindle cell proliferation. We present a case of a 30-year-old man who developed an irregular, purple, tender plaque measuring 2.5 cm on the right pretibial region. Wide excision of the right leg lesion showed superficial spreading melanoma with epithelioid cells and no spindle cell component. Sentinel lymph node (SLN) biopsy showed an atypical melanocytic proliferation involving one inguinal lymph node with subcapsular and intraparenchymal components. There were spindled tumor cells in lymph node capsule with hyperchromatic nuclei, which were nested within desmoplastic stroma, and were S100- and SOX10-positive and MART1- and HMB-45 negative; in addition to epithelioid tumor cells, which were S100-, SOX10-, and MART1-positive. Multiple discontinuous foci, subcapsular atypical melanocytes, and extracapsular extension helped in excluding capsular nevus. These findings were consistent with DM. Herein, we present an unusual case of primary cutaneous superficial spreading melanoma of the right leg with a predominantly epithelioid morphology that developed metastases to the SLN. The metastasis exhibited divergent differentiation, including both epithelioid morphology identical to the primary, but with additional features of DM that were nonoverlapping with the primary lesion.
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http://dx.doi.org/10.1097/DAD.0000000000001898DOI Listing
January 2021

Urethral involvement is associated with higher mortality and local recurrence in vulvar melanoma: a single institutional experience.

Hum Pathol 2020 10 20;104:1-8. Epub 2020 Jul 20.

Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA. Electronic address:

Vulvar malignant melanoma (VMM), although uncommon, comprises 5-10% of all vulvar malignancies. Local control is notoriously poor in VMM with recurrence rates of 30-50% compared with approximately 3% in cutaneous melanomas. We studied clinicopathologic features of 37 women with VMM, after reviewing three decades of clinical follow-up data in our institutional databases. Most patients were Caucasian (n = 35) with an average age at diagnosis of 60.6 years (range 23-83). The most common subtype was mucosal lentiginous melanoma (n = 25). We compared Kaplan-Meier survival curves of 31 patients defined by clinical and microscopic attributes using exact log-rank tests. Younger patients at diagnosis (23-64 years), those with thin melanomas (≤1 mm), and those with Clark's level II or III tumors had better 5-year survival rates than older patients (65-83 years) and those with thick melanomas (>1 mm) and those with Clark's level IV or V (P ≤ 0.05), respectively, by exact log-rank test. Local recurrence of melanoma occurred in 15 patients. Nine patients (24%) had eventual urethral involvement by malignant melanoma, and this feature was associated with significantly shorter survival (P = 0.036). Patients with urethral involvement had shorter median time to death and worse 5-year survival rates. Given that spread to the urethra is common in VMM and urethral recurrence is also associated with mortality, pathology excision specimens should be carefully reviewed with attention to urethral involvement as a potentially important prognostic factor.
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http://dx.doi.org/10.1016/j.humpath.2020.07.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669565PMC
October 2020

Bleeding Umbilical Papule: Answer.

Am J Dermatopathol 2020 Mar;42(3):224

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

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http://dx.doi.org/10.1097/DAD.0000000000001314DOI Listing
March 2020

Characterization of the inflammatory features of central centrifugal cicatricial alopecia.

J Cutan Pathol 2020 Jun 6;47(6):530-534. Epub 2020 Mar 6.

Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

Central centrifugal cicatricial alopecia (CCCA) is a scarring alopecia that primarily affects women of African descent. Although histopathological features of CCCA have been described, the pathophysiology of this disease remains unclear. To better understand the components of CCCA pathophysiology, we evaluated the composition of the inflammatory infiltrate, the distribution of Langerhans cells (LCs), and the relationship between fibrosis and perifollicular vessel distribution. Our data indicate that CCCA is associated with a CD4-predominant T-cell infiltrate with increased LCs extending into the lower hair follicle. Fibroplasia associated with follicular scarring displaces blood vessels away from the outer root sheath epithelium. These data indicate that CCCA is an inflammatory scarring alopecia with unique pathophysiologic features that differentiate it from other lymphocytic scarring processes.
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http://dx.doi.org/10.1111/cup.13666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401378PMC
June 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

Pigmented onychomatricoma mimicking nail unit melanoma.

J Cutan Pathol 2019 Dec;46(12):895-897

Department of Dermatology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.

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http://dx.doi.org/10.1111/cup.13529DOI Listing
December 2019

There is fat in this sclerosis: A case report of sclerotic lipoma and review of the literature.

J Cutan Pathol 2020 Mar 29;47(3):286-290. Epub 2019 Oct 29.

Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Sclerotic lipomas, a lipoma variant, are benign subcutaneous tumors, so-named because of their resemblance to sclerotic fibromas. Previous literature has suggested that these tumors may show a predilection for middle-aged adult males. We report an unusual case of a sclerotic lipoma diagnosed on the scalp of a 66-year-old female. The patient presented to the outpatient clinic with a 3- to 4-year history of an enlarging and irritated 2.6-cm nodule on the anterior crown of the scalp, clinically thought to be a pilar cyst. Histopathological examination from the excisional specimen revealed a well-circumscribed dermal to subcutaneous tumor with ample sclerotic collagen bundles, an increased number of CD34 positive spindled cells, and prominent S-100 positive mature adipocytes comprising greater than 50% of the tumor. We present this case given its atypical clinical and histopathological presentation, review the literature of sclerotic lipomas, and discuss the differential diagnosis to raise awareness of this rare entity.
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http://dx.doi.org/10.1111/cup.13593DOI Listing
March 2020

Genome-wide screening of mouse knockouts reveals novel genes required for normal integumentary and oculocutaneous structure and function.

Sci Rep 2019 08 1;9(1):11211. Epub 2019 Aug 1.

Department of Ophthalmology & Vision Science, School of Medicine, University of California Davis, Sacramento, CA, United States.

Oculocutaneous syndromes are often due to mutations in single genes. In some cases, mouse models for these diseases exist in spontaneously occurring mutations, or in mice resulting from forward mutatagenesis screens. Here we present novel genes that may be causative for oculocutaneous disease in humans, discovered as part of a genome-wide screen of knockout-mice in a targeted single-gene deletion project. The International Mouse Phenotyping Consortium (IMPC) database (data release 10.0) was interrogated for all mouse strains with integument abnormalities, which were then cross-referenced individually to identify knockouts with concomitant ocular abnormalities attributed to the same targeted gene deletion. The search yielded 307 knockout strains from unique genes with integument abnormalities, 226 of which have not been previously associated with oculocutaneous conditions. Of the 307 knockout strains with integument abnormalities, 52 were determined to have ocular changes attributed to the targeted deletion, 35 of which represent novel oculocutaneous genes. Some examples of various integument abnormalities are shown, as well as two examples of knockout strains with oculocutaneous phenotypes. Each of the novel genes provided here are potentially relevant to the pathophysiology of human integumentary, or oculocutaneous conditions, such as albinism, phakomatoses, or other multi-system syndromes. The novel genes reported here may implicate molecular pathways relevant to these human diseases and may contribute to the discovery of novel therapeutic targets.
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http://dx.doi.org/10.1038/s41598-019-47286-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6672016PMC
August 2019

Launching lollipops? Perforating osteoma cutis in nephrogenic systemic fibrosis.

J Cutan Pathol 2019 Jul;46(7):467-470

Department of Dermatology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.

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http://dx.doi.org/10.1111/cup.13409DOI Listing
July 2019

Bleeding Umbilical Papule: Challenge.

Am J Dermatopathol 2020 Mar;42(3):e34-e35

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

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http://dx.doi.org/10.1097/DAD.0000000000001312DOI Listing
March 2020

Syphilitic Alopecia.

N Engl J Med 2018 Oct;379(17):1657

Hospital of the University of Pennsylvania, Philadelphia, PA

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http://dx.doi.org/10.1056/NEJMicm1804118DOI Listing
October 2018

Viral oncoprotein antibodies as a marker for recurrence of Merkel cell carcinoma: A prospective validation study.

Cancer 2017 04 7;123(8):1464-1474. Epub 2016 Dec 7.

Division of Dermatology, Department of Medicine, University of Washington, Seattle, Washington.

Background: Merkel cell carcinoma (MCC) is an aggressive skin cancer with a recurrence rate of >40%. Of the 2000 MCC cases per year in the United States, most are caused by the Merkel cell polyomavirus (MCPyV). Antibodies to MCPyV oncoprotein (T-antigens) have been correlated with MCC tumor burden. The present study assesses the clinical utility of MCPyV-oncoprotein antibody titers for MCC prognostication and surveillance.

Methods: MCPyV-oncoprotein antibody detection was optimized in a clinical laboratory. A cohort of 219 patients with newly diagnosed MCC were followed prospectively (median follow-up, 1.9 years). Among the seropositive patients, antibody titer and disease status were serially tracked.

Results: Antibodies to MCPyV oncoproteins were rare among healthy individuals (1%) but were present in most patients with MCC (114 of 219 patients [52%]; P < .01). Seropositivity at diagnosis independently predicted decreased recurrence risk (hazard ratio, 0.58; P = .04) in multivariate analyses adjusted for age, sex, stage, and immunosuppression. After initial treatment, seropositive patients whose disease did not recur had rapidly falling titers that became negative by a median of 8.4 months. Among seropositive patients who underwent serial evaluation (71 patients; 282 time points), an increasing oncoprotein titer had a positive predictive value of 66% for clinically evident recurrence, whereas a decreasing titer had a negative predictive value of 97%.

Conclusions: Determination of oncoprotein antibody titer assists in the clinical management of patients with newly diagnosed MCC by stratifying them into a higher risk seronegative cohort, in which radiologic imaging may play a more prominent role, and into a lower risk seropositive cohort, in which disease status can be tracked in part by oncoprotein antibody titer. Cancer 2017;123:1464-1474. © 2016 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.30475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384867PMC
April 2017

Polyomavirus-Negative Merkel Cell Carcinoma: A More Aggressive Subtype Based on Analysis of 282 Cases Using Multimodal Tumor Virus Detection.

J Invest Dermatol 2017 04 1;137(4):819-827. Epub 2016 Nov 1.

Division of Dermatology, Department of Medicine, University of Washington, Seattle, Washington, USA; Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. Electronic address:

Previous studies have reached conflicting conclusions regarding the proportion of Merkel cell carcinomas (MCCs) that contain the Merkel cell polyomavirus (MCPyV) and the clinical significance of tumor viral status. To address these controversies, we detected MCPyV large T antigen using immunohistochemistry with two distinct antibodies and MCPyV DNA using quantitative PCR. Tumors were called MCPyV-positive if two or more of these three assays indicated presence of this virus. A total of 53 of 282 (19%) MCC tumors in this cohort were virus-negative using this multimodal system. Immunohistochemistry with the CM2B4 antibody had the best overall performance (sensitivity = 0.882, specificity = 0.943) compared with the multimodal classification. Multivariate analysis including age, sex, and immunosuppression showed that, relative to MCC patients with virus-positive tumors, virus-negative MCC patients had significantly increased risk of disease progression (hazard ratio = 1.77, 95% confidence interval = 1.20-2.62) and death from MCC (hazard ratio = 1.85, 95% confidence interval = 1.19-2.89). We confirm that approximately 20% of MCCs are not driven by MCPyV and that such virus-negative MCCs, which can be quite reliably identified by immunohistochemistry using the CM2B4 antibody alone, represent a more aggressive subtype that warrants closer clinical follow-up.
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http://dx.doi.org/10.1016/j.jid.2016.10.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5565758PMC
April 2017

Milestones in the staging, classification, and biology of Merkel cell carcinoma.

J Natl Compr Canc Netw 2014 Sep;12(9):1255-62

From the School of Medicine, School of Public Health, Institute for Translational Health Sciences, Department of Medicine/Dermatology, and Department of Pathology, University of Washington; Clinical Research Division, Fred Hutchinson Cancer Research Center; and Seattle Cancer Care Alliance, Seattle, Washington. From the School of Medicine, School of Public Health, Institute for Translational Health Sciences, Department of Medicine/Dermatology, and Department of Pathology, University of Washington; Clinical Research Division, Fred Hutchinson Cancer Research Center; and Seattle Cancer Care Alliance, Seattle, Washington. From the School of Medicine, School of Public Health, Institute for Translational Health Sciences, Department of Medicine/Dermatology, and Department of Pathology, University of Washington; Clinical Research Division, Fred Hutchinson Cancer Research Center; and Seattle Cancer Care Alliance, Seattle, Washington. From the School of Medicine, School of Public Health, Institute for Translational Health Sciences, Department of Medicine/Dermatology, and Department of Pathology, University of Washington; Clinical Research Division, Fred Hutchinson Cancer Research Center; and Seattle Cancer Care Alliance, Seattle, Washington. From the School of Medicine, School of Public Health, Institute for Translational Health Sciences, Department of Medicine/Dermatology, and Department of Pathology, University of Washington; Clinical Research Division, Fred Hutchinson Cancer Research Center; and Seattle Cancer Care Alliance, Seattle, Washington.

Merkel cell carcinoma (MCC) is an aggressive skin cancer that is causally associated with ultraviolet light exposure and a recently discovered polyomavirus. Before 2010, MCC was staged using any of 5 unique systems in active use. In 2010, a consensus staging system for MCC was adopted worldwide and replaced these systems. This consensus system includes substages that reflect prognostic differences based on whether nodal evaluation was performed by pathologic analysis or clinical assessment alone. MCC-specific disease classification in ICD-9, to be expanded in the upcoming ICD-10, has improved the ability to track and manage this malignancy. Several biomarkers and histopathologic features have been identified that improve understanding of this cancer and may lead to future refinement of the current staging system. In 2008, the Merkel cell polyomavirus was discovered and is now thought to be a critical mechanism of transformation in at least 80% of MCCs. In patients who produce antibodies to the viral T-antigen oncoprotein, the titer increases and decreases with MCC disease burden and can be a clinically useful marker of recurrence. Diverse studies link CD8-positive T-cell function with outcomes in MCC and serve as the rational basis for ongoing trials of therapies to augment cellular immunity. This article reviews basic and translational research insights that will lead to improved staging, prognostic accuracy, and mechanism-based therapy for this often-lethal skin cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4161960PMC
http://dx.doi.org/10.6004/jnccn.2014.0123DOI Listing
September 2014