Publications by authors named "Victor G Prieto"

398 Publications

Histologic Patterns of Cutaneous Metastases of Breast Carcinoma: A Clinicopathologic Study of 232 Cases.

Am J Dermatopathol 2021 Jun;43(6):401-411

Professor, Departments of Pathology, Medical College of Wisconsin, Milwaukee, WI.

Abstract: Cutaneous metastasis may be the initial sign of internal malignancy but more often represents a late manifestation of widely disseminated disease. Breast carcinoma is the most common malignancy to metastasize to the skin. Although several studies have detailed the histopathologic patterns of cutaneous metastasis from internal malignancies, very little has been published regarding metastases of breast carcinoma to the skin. Furthermore, the histopathologic and clinical features observed in the cases of breast carcinoma with local skin involvement as opposed to cases exhibiting distant cutaneous metastases have not been adequately investigated. We have reviewed 232 cases of breast carcinoma with cutaneous metastases from 2 large institutions. All cases of carcinoma of the breast with involvement of the skin of the anterior chest wall were compared with those with distant cutaneous metastases. Two hundred thirty-two cases in 199 patients were included, of which 126 had skin involvement exclusively involving the ipsilateral anterior chest, and 106 had biopsy-proven distant cutaneous metastases. Twelve patients had both local and distal spread. Distant cutaneous metastases showed a predilection for the contralateral anterior chest wall area, followed by the head and neck, back, and abdomen. Histologically, most of the tumors presented in this series showed features of infiltrating ductal carcinoma. In both ipsilateral and distant metastases, the tumors demonstrated little change in histologic features from the primary lesion; however, the distant metastases showed a tendency to display more poorly differentiated features. The mean patient survival when cutaneous involvement was localized to the skin of the anterior chest wall was 23 months as compared with 20.6 months when distant sites were affected. A comparison of the clinicopathologic features of the patients presented in this series suggests that alternate biological mechanisms may apply for local and distant skin metastases from breast carcinoma.
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http://dx.doi.org/10.1097/DAD.0000000000001841DOI Listing
June 2021

In memoriam: N. Scott McNutt, MD.

J Cutan Pathol 2021 Jul 12;48(7):827-828. Epub 2021 May 12.

Department of Medicine, University of Chicago, Chicago, Illinois, USA.

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http://dx.doi.org/10.1111/cup.14031DOI Listing
July 2021

Tumor Lysis Syndrome: Introduction of a Cutaneous Variant and a New Classification System.

Cureus 2021 Mar 11;13(3):e13816. Epub 2021 Mar 11.

Center for Personalized Cancer Therapy, University of California San Diego Moores Cancer Center, La Jolla, USA.

Tumor lysis syndrome, an oncological emergency, is characterized by laboratory parameters such as hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia, as well as renal injury with an elevated creatinine. Tumor lysis syndrome is seen in patients with aggressive malignancies and high tumor burden. More frequently, it occurs in individuals with hematologic malignancies such as high-grade lymphomas (such as Burkitt lymphoma) and leukemia (such as acute lymphocytic leukemia). It also, albeit less commonly, can be seen in patients with widespread solid tumors that are rapidly proliferating and are markedly sensitivity to antineoplastic therapy. Tumor lysis syndrome is usually preceded by cancer-directed therapy; however, the syndrome can present spontaneously prior to the individual receiving malignancy-directed treatment. We reported a man with metastatic salivary duct carcinoma who had cutaneous metastases that presented as carcinoma hemorrhagiectoides. Microscopic examination demonstrated that the metastatic tumor cells had infiltrated and replaced the entire dermis. After the patient received his first dose of antineoplastic therapy, he had an excellent response and the cutaneous metastases developed into ulcers; we hypothesize that most of the dermis, which had been replaced by tumor cells, disappeared as a result of the therapeutic response, and the overlying epidermis became necrotic and shed, leaving an ulcer. His dramatic response to treatment prompted us to propose a new classification of tumor lysis syndrome, which should include the systemic form of the condition as well as the new variant: cutaneous tumor lysis syndrome. We anticipate that, with improvement in targeted therapies, there may be an increase in therapy-associated cutaneous tumor lysis syndrome.
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http://dx.doi.org/10.7759/cureus.13816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038896PMC
March 2021

Melanocytic lesions with blue naevus-like (dendritic) morphology: an update with an emphasis on histopathological, immunophenotypic, and molecular features.

Histopathology 2021 Mar 27. Epub 2021 Mar 27.

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

An accurate diagnosis of melanocytic lesions requires a thorough histopathological evaluation accompanied by appropriate correlation with clinical examination findings. Although most melanocytic lesions can readily be classified as one of the defined diagnostic entities according to well-established diagnostic criteria, a subset of melanocytic lesions, particularly those with blue naevus-like (pigmented dendritic) morphology, have notoriously constituted an enduring challenge for pathologists. These lesions are rare and often show histological ambiguities, with features of both benignity and malignancy, thereby making accurate risk assessment and prediction of their biological behaviours difficult on histological grounds alone. Herein, we outline a practical and systematic approach for the diagnosis of melanocytic lesions with dendritic morphology, with a particular focus on histological and immunophenotypic features that help to distinguish one entity from another. In this review, we provide the most current knowledge on these melanocytic lesions in the literature and our experience with these rare entities, and we discuss the utility of molecular techniques as an ancillary tool, especially in histologically ambiguous and/or borderline lesions.
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http://dx.doi.org/10.1111/his.14371DOI Listing
March 2021

Metaplasia mimicking malignancy: A challenging case of florid eccrine squamous syringometaplasia.

J Cutan Pathol 2021 Jul 1;48(7):995-998. Epub 2021 Apr 1.

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

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http://dx.doi.org/10.1111/cup.14015DOI Listing
July 2021

Is immunohistochemical expression of GATA3 helpful in the differential diagnosis of transformed mycosis fungoides and primary cutaneous CD30-positive T cell lymphoproliferative disorders?

Virchows Arch 2021 Feb 18. Epub 2021 Feb 18.

Department of Pathology, Dermatopathology Section, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Mycosis fungoides with large cell transformation (MFLCT) can be difficult to distinguish from primary cutaneous CD30+ T cell lymphoproliferative disorders (PC CD30+ LPD), especially primary cutaneous anaplastic large cell lymphoma (PC-ALCL). This diagnostic distinction is critical for appropriate patient management. GATA3 has been proposed to be useful in the discrimination between these two entities. We identified 25 cases of MFLCT and 24 cases of PC CD30+ LPDs (including lymphomatoid papulosis (n=14), PC-ALCL (n=6), and CD30+ LPD, not otherwise specified (n=4)) diagnosed at our institution from 2002 to 2019. Sections from archived specimens were stained to evaluate for GATA3 expression by immunohistochemistry and compared among cutaneous CD30+ T cell LPDs. The majority of the MFLCT cohort had strong, diffuse expression of GATA3 ranging from 0 to 100% of dermal T cells (mean 53.20%) with 15/25 cases (60%) showing GATA3 expression greater than 50%, while the PC CD30+ LPD group showed variable, moderate GATA3 labeling ranging from 0 to 60% of dermal T cells (mean 23.26%), with 5/6 cases (83%) showing GATA3 expression less than 40% (p =0.003). The calculated sensitivity and specificity were 56% and 74%, while positive and negative predictive values were 70% and 61%, respectively. Based on the percent staining of positive cells, using 50% as a cutoff value for expression, GATA3 might be a useful immunohistochemical marker to discriminate MFLCT from PC CD30+ LPDs, including PC-ALCL.
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http://dx.doi.org/10.1007/s00428-021-03056-yDOI Listing
February 2021

Discordance in Diagnosis of Melanocytic Lesions and Its Impact on Clinical Management.

Arch Pathol Lab Med 2021 Feb 12. Epub 2021 Feb 12.

From the Departments of Pathology (Ronen, Al-Rohil, Keiser, Jour, Nagarajan, Tetzlaff, Curry, Ivan, Middleton, Torres-Cabala, Aung, Prieto).

Context.—: Accurate diagnosis of melanocytic lesions is fundamental for appropriate clinical management.

Objective.—: To evaluate the degree of discordance, if any, between histopathologic diagnoses of melanocytic lesions at referring institutions and at a tertiary referral cancer center and the potential impact of such discordance on clinical management.

Design.—: We retrospectively identified all patients referred to our comprehensive cancer center for evaluation of a melanocytic lesion from January 2010 to January 2011. For each patient, the histopathologic diagnosis from the referring institution was compared with the histopathologic diagnosis from a dermatopathologist at our center. Discordances were classified as major if they resulted in a change in clinical management and minor if they did not.

Results.—: A total of 1521 cases were included. The concordance rates were 72.2% (52 of 72) for dysplastic nevus, 75.0% (15 of 20) for all other types of nevi, 91.1% (143 of 157) for melanoma in situ, 96.1% (758 of 789) for invasive melanoma, and 99.6% (478 of 480) for metastatic melanoma. Major discordances were found in 20.2% of cases (307 of 1521), and minor discordances were found in 48.8% of cases (742 of 1521). Compared with the guideline-based treatment recommendation based on the referring-institution diagnosis, the guideline-based treatment recommendation based on the cancer center diagnosis was more extensive in 5.9% (89 of 1521) of patients and less extensive in 5.0% (76 of 1521) of patients.

Conclusions.—: Our findings underscore the importance of secondary histopathologic review of melanocytic lesions by expert dermatopathologists because significant changes in the diagnosis, tumor classification, and/or staging may be identified; thus, resulting in critical changes in recommendations for clinical management.
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http://dx.doi.org/10.5858/arpa.2020-0620-OADOI Listing
February 2021

Perianal condylomata lata mimicking carcinoma.

J Cutan Pathol 2021 Jan 20. Epub 2021 Jan 20.

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

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http://dx.doi.org/10.1111/cup.13865DOI Listing
January 2021

Standardized Method for Defining a 1-mm2 Region of Interest for Calculation of Mitotic Rate on Melanoma Whole Slide Images.

Arch Pathol Lab Med 2021 Jan 8. Epub 2021 Jan 8.

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

Context.—: Mitotic rate counting is essential in pathologic evaluations in melanoma. The American Joint Committee on Cancer recommends reporting the number of mitotic figures (MFs) in a 1-mm2 area encompassing the "hot spot." There is currently no standard procedure for delineating a 1-mm2 region of interest for MF counting on a digital whole slide image (WSI) of melanoma.

Objective.—: To establish a standardized method to enclose a 1-mm2 region of interest for MF counting in melanoma based on WSIs and assess the method's effectiveness.

Design.—: Whole slide images were visualized using the ImageScope viewer (Aperio). Different monitors and viewing magnifications were explored and the annotation tools provided by ImageScope were evaluated. For validation, we compared mitotic rates obtained from WSIs with our method and those from glass slides with traditional microscopy with 30 melanoma cases.

Results.—: Of the monitors we examined, a 32-inch monitor with 3840 × 2160 resolution was optimal for counting MFs within a 1-mm2 region of interest in melanoma. When WSIs were viewed in the ImageScope viewer, ×10 to ×20 magnification during screening could efficiently locate a hot spot and ×20 to ×40 magnification during counting could accurately identify MFs. Fixed-shape annotations with 500 × 500-μm squares or circles can precisely and efficiently enclose a 1-mm2 region of interest. Our method on WSIs was able to produce a higher mitotic rate than with glass slides.

Conclusions.—: Whole slide images may be used to efficiently count MFs. We recommend fixed-shape annotation with 500 × 500-μm squares or circles for routine practice in counting MFs for melanoma.
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http://dx.doi.org/10.5858/arpa.2020-0137-OADOI Listing
January 2021

Positive Job Search Experience for New Pathologists Seeking First Employment Between 2017-2019.

Arch Pathol Lab Med 2021 Jan 8. Epub 2021 Jan 8.

the Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee (Hoffman).

Context.—: An aging population calls for an adequate response in the workforce of medical professionals. The field of pathology has seen a downward trend in numbers of graduating US allopathic medical students choosing the specialty. Concerns about the job market after residency and fellowship graduation may be a contributing factor.

Objective.—: To provide an update on the trends emerging from a survey of pathology graduates' job search experience for their first nonfellowship position.

Design.—: Data from an annual job search survey sent by The College of American Pathologists Graduate Medical Education Committee between 2017 and 2019 to The College of American Pathologists junior members and fellows in practice 3 years or less, actively looking for a nonfellowship position, was analyzed. Various indicators of the job search experience were compared year to year and with the previously published 2012 to 2016 benchmark data.

Results.—: Analysis revealed positive trends between the 2017 to 2019 data and the 2012 to 2016 benchmark data, including participants' perceiving more ease in finding a position, improved availability of jobs in their subspecialty choice, and higher ratings of satisfaction with the position accepted, as well as a greater proportion of respondents finding a position within 6 months of initiating their job search.

Conclusions.—: The job market for pathology residents and fellows looking for their first nonfellowship position has improved with respect to multiple indicators, such as ease of finding a position, length of job search, and satisfaction with the position accepted when comparing 2017 to 2019 data with the 2012 to 2016 benchmark data.
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http://dx.doi.org/10.5858/arpa.2020-0455-CPDOI Listing
January 2021

Tertiary lymphoid structures with overlapping histopathologic features of cutaneous marginal zone lymphoma during neoadjuvant cemiplimab therapy are associated with antitumor response.

J Cutan Pathol 2021 May 13;48(5):674-679. Epub 2021 Jan 13.

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

The development of immune checkpoint inhibitor (ICI) therapy with anti-CTLA-4 and anti-PD-1/L1 monoclonal antibodies has led to a paradigm shift in cancer therapy. ICI neoadjuvant therapy followed by surgery has become the standard of care for several advanced-stage cancers. The pathology associated with ICI therapy is vast and includes neoadjuvant-associated tissue reactions and activation of tertiary lymphoid structures (TLSs) at the site of the tumor bed and off-target immune-related adverse events. TLSs are thought to recapitulate lymph node function and may act as localized immune machinery to mount an antitumor response. B-cell activation in TLSs during neoadjuvant ICI therapy has been correlated with antitumor response. We report a patient with a history of sarcomatoid squamous cell carcinoma treated with neoadjuvant ICI cemiplimab who developed clonal expansion of B-cells in the TLSs of the tumor bed. The TLSs morphologically mimicked a cutaneous marginal zone lymphoma with plasmacytic differentiation. Awareness of clonal expansion of B-cells in TLSs during neoadjuvant ICI therapy is critical to recognize a response to ICI therapy and to avoiding an incorrect diagnosis of low-grade B-cell lymphoma.
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http://dx.doi.org/10.1111/cup.13953DOI Listing
May 2021

Prognostic Significance of Subungual Anatomic Site in Acral Lentiginous Melanoma.

Arch Pathol Lab Med 2020 Dec 8. Epub 2020 Dec 8.

From the Department of Pathology (Mejbel, Torres-Cabala, Ivan, Nagarajan, Curry, Prieto, Aung), The University of Texas MD Anderson Cancer Center, Houston.

Context.—: Acral lentiginous melanoma is a rare and aggressive type of cutaneous melanoma that arises on the acral skin and the nail unit. The prognostic significance of subungual anatomic site in acral lentiginous melanoma is not established.

Objective.—: To assess the impact of subungual anatomic site on overall survival and disease-specific survival in acral lentiginous melanoma.

Design.—: Retrospective cohort analysis. Clinicopathologic characteristics of 627 primary acral lentiginous melanomas (45 [7%] subungual and 582 [93%] nonsubungual) were summarized, and the impact of these characteristics on overall survival and disease-specific survival was determined using univariate and multivariable analyses.

Results.—: No significant differences in clinicopathologic features were identified between the subungual and nonsubungual acral lentiginous melanomas. The 1-, 5-, and 10-year overall survival rates were 81%, 40%, and 28%, respectively, for subungual acral lentiginous melanoma and 94%, 59%, and 38%, respectively, for nonsubungual acral lentiginous melanoma (P = .04); risk of death was significantly higher for subungual tumors (hazard ratio [95% confidence interval] = 1.59 [1.02-2.50]; P = .04). The 1-, 5-, and 10-year disease-specific survival rates were 94%, 56%, and 48%, respectively, for subungual acral lentiginous melanoma versus 96%, 69%, and 55%, respectively, for nonsubungual acral lentiginous melanoma (P = .18). By multivariable analysis, independent poor prognostic factors included older age and ulceration for overall survival and greater Breslow thickness and sentinel lymph node positivity for overall survival and disease-specific survival. Subungual anatomic site was not an independent prognostic factor for overall or disease-specific survival.

Conclusions.—: Subungual anatomic site is not an independent prognostic factor for acral lentiginous melanoma.
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http://dx.doi.org/10.5858/arpa.2020-0308-OADOI Listing
December 2020

Male Mammary Paget Disease: A Tale of 2 Contrasting Cases.

Am J Dermatopathol 2020 Dec;42(12):981-985

Departments of Pathology.

Mammary Paget disease (MPD) comprises 1.45% all male breast cancers, compared with only 0.68% of all female breast cancers. Patients usually present in the fifth and sixth decades of life with ulceration, eczematous changes, discharge, bleeding, itching, and induration of the nipple and areola. Typically, there is a delay in definitive diagnosis and treatment from the onset of symptoms because most patients are initially treated for a rash. At the time of diagnosis, about half of the patients may have palpable breast mass, positive lymph nodes, or both. In this article, we present 2 cases of male MPD representing the extremes of clinical, radiologic, and histopathologic spectrum of the disease. One patient presented with a rash of the nipple of several months duration without an underlying lesion, whereas the other presented with sensitivity and pain of the nipple for 1 year and an underlying mass. Biopsies were diagnostic of MPD in both cases, and definitive surgery revealed an underlying ductal carcinoma in situ in the first case and an invasive ductal carcinoma in the second, highlighting the importance of early biopsy to initiate appropriate management.
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http://dx.doi.org/10.1097/DAD.0000000000001799DOI Listing
December 2020

Factors Influencing US Allopathic Medical Students to Choose Pathology as a Specialty.

Acad Pathol 2020 Jan-Dec;7:2374289520951924. Epub 2020 Sep 14.

Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA.

The SARS-CoV-2 pandemic has highlighted the crucial role of pathologists in the health care system at a time of significant decline in the number of US medical students matching to pathology residency positions. To understand this decline, a national survey of fourth-year US allopathic medical students was conducted to assess experiences, knowledge, and attitudes of pathology and factors that impact specialty choice. Participating in a separate pathology course did not increase the probability of choosing pathology. Experiences significantly associated with choosing pathology included clinical or research opportunities in pathology during the last 2 years of medical school, autopsy observation/participation, and participation in pathology interest groups. Many respondents felt they were not sufficiently exposed to pathology to consider it as a specialty. Those who considered pathology but did not choose it were less likely to report understanding the activities of pathologists and being recruited by pathology faculty and more likely to express a preference for more direct patient contact as compared to those entering pathology. In general, respondents agreed that pathology has a good work-life balance and a satisfying degree of intellectual challenge. On the other hand, respondents generally agreed that information on social media and perception of the pathology job market do not seem to be positive and few agreed that pathology is a highly regarded specialty. We identify steps to address these issues and increase the number of US medical students choosing pathology as a specialty crucial to the future of medicine and public health.
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http://dx.doi.org/10.1177/2374289520951924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557358PMC
September 2020

Telomerase Reverse Transcriptase Protein Expression Is More Frequent in Acral Lentiginous Melanoma Than in Other Types of Cutaneous Melanoma.

Arch Pathol Lab Med 2021 Jul;145(7):842-850

From the Departments of Pathology (Cho, Wang, Nagarajan, Curry, Ivan, Lazar, Prieto, Torres-Cabala, Aung), The University of Texas MD Anderson Cancer Center, Houston.

Context.—: Molecularly distinct from cutaneous melanomas arising from sun-exposed sites, acral lentiginous melanomas (ALMs) typically lack ultraviolet-signature mutations, such as telomerase reverse transcriptase (TERT) promoter mutations. Instead, ALMs show a high degree of copy number alterations, often with multiple amplifications of TERT, which are associated with adverse prognosis. The prognostic value of TERT protein expression in acral melanomas, however, is not established.

Objective.—: To evaluate the frequency and pattern of TERT immunoreactivity and assess the potential utility of TERT expression as a prognostic indicator in ALMs.

Design.—: TERT expression by immunohistochemistry was analyzed in a series of 57 acral and nonacral melanocytic lesions, including 24 primary and 6 metastatic ALMs. Clinical outcome in patients with ALMs by TERT expression was assessed.

Results.—: TERT expression was more frequent in ALMs than in nonlentiginous acral melanomas and nonacral cutaneous melanomas, and was absent in acral nevi (P = .01). When present, TERT expression in ALMs was cytoplasmic and more intense than TERT expression in other melanocytic lesions (P = .05) with a higher H-score (P = .01). There was a trend toward decreased overall survival in patients with ALMs with TERT immunoreactivity, but it did not reach statistical significance. Furthermore, no correlation was found between TERT expression and disease-specific survival in patients with ALMs.

Conclusions.—: Although TERT protein expression was frequently detected in both primary and metastatic ALMs, TERT immunoreactivity in ALMs did not correlate with survival in our study. Further studies with larger cohorts are needed to elucidate the prognostic value of TERT expression in ALMs.
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http://dx.doi.org/10.5858/arpa.2020-0330-OADOI Listing
July 2021

TRPS1: a highly sensitive and specific marker for breast carcinoma, especially for triple-negative breast cancer.

Mod Pathol 2021 04 3;34(4):710-719. Epub 2020 Oct 3.

Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.

Currently there is no highly specific and sensitive marker to identify breast cancer-the most common malignancy in women. Breast cancer can be categorized as estrogen receptor (ER)/progesterone receptor (PR)-positive luminal, human epidermal growth factor receptor 2 (HER2)-positive, or triple-negative breast cancer (TNBC) types based on the expression of ER, PR, and HER2. Although GATA3 is the most widely used tumor marker at present to determine the breast origin, which has been shown to be an excellent marker for ER-positive and low-grade breast cancer, but it does not work well for TNBC with sensitivity as low as <20% in metaplastic breast carcinoma. In the current study, through TCGA data mining we identified trichorhinophalangeal syndrome type 1 (TRPS1) as a specific gene for breast carcinoma across 31 solid tumor types. Moreover, high mRNA level of TRPS1 was found in all four subtypes of breast carcinoma including ER/PR-positive luminal A and B types, HER2-positive type, and basal-type/TNBC. We then analyzed TRPS1 expression in 479 cases of various types of breast cancer using immunochemistry staining, and found that TRPS1 and GATA3 had comparable positive expression in ER-positive (98% vs. 95%) and HER2-positive (87% vs. 88%) breast carcinomas. However, TRPS1 which was highly expressed in TNBC, was significantly higher than GATA3 expression in metaplastic (86% vs. 21%) and nonmetaplastic (86% vs. 51%) TNBC. In addition, TRPS1 expression was evaluated in 1234 cases of solid tumor from different organs. In contrast to the high expression of GATA3 in urothelial carcinoma, TRPS1 showed no or little expression in urothelial carcinomas or in other tumor types including lung adenocarcinoma, pancreatic adenocarcinoma, colon and gastric adenocarcinoma, renal cell carcinoma, melanoma, and ovarian carcinoma. These findings suggest that TRPS1 is a highly sensitive and specific marker for breast carcinoma and can be used as a great diagnostic tool, especially for TNBC.
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http://dx.doi.org/10.1038/s41379-020-00692-8DOI Listing
April 2021

Transition From a Standard to a Hybrid On-Site and Remote Anatomic Pathology Training Model During the Coronavirus Disease 2019 (COVID-19) Pandemic.

Arch Pathol Lab Med 2021 01;145(1):22-31

Department of Pathology (Chin, Kwon, Gan, Ramalingam, Prieto, Aung), The University of Texas MD Anderson Cancer Center, Houston.

Context.—: As teaching hospitals institute social distancing and defer nonemergent procedures to cope with the coronavirus disease 2019 pandemic, the need for daily on-site presence, unless necessary, has been reduced for all medical staff, including trainees. Pathology training programs must adapt to these changes to ensure overall safety without significantly compromising training and the educational mission of the institution.

Objective.—: To describe the hybrid on-site and remote anatomic pathology training model in response to the coronavirus disease 2019 pandemic that was implemented in our pathology department and report the clinical fellows' responses to the survey about their experiences.

Design.—: The hybrid model was implemented March 25, 2020. Fellows alternate weekly between working on site and working remotely. On site, fellows wear personal protective equipment and maintain social distancing. Remotely, fellows use digital pathology to review cases and supplement with online educational activities. Virtual "coffee breaks," meditation, and exercise are part of the curriculum. Online platforms, including WebEx, Google Classroom, and Canvas, are used to continue educational activities. The survey was open May 19 through June 8, 2020.

Results.—: Twenty-eight of the 29 clinical fellows (96%) responded. Many of the respondents indicated substantial increase in their skill with using digital pathology and online platforms during the pandemic. The top most helpful resources were the United States and Canadian Academy of Pathology interactive microscopy courses (found very or somewhat helpful by 22 of 23 clinical fellows; 96%), ExpertPath (19 of 23; 82%), the College of American Pathologists virtual learning series (18 of 23; 78%), the World Health Organization Blue Books (16 of 23; 70%), the American Society of Cytopathology webinars (14 of 23; 61%), and our institutional digital slide collection (12 of 23; 52%).

Conclusions.—: Hybrid on-site and remote training can maximize anatomic pathology learning opportunities while maintaining the safety of trainees, hospital personnel, and the community.
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http://dx.doi.org/10.5858/arpa.2020-0467-SADOI Listing
January 2021

Clinical validity of a gene expression signature in diagnostically uncertain neoplasms.

Per Med 2020 09 17;17(5):361-371. Epub 2020 Jun 17.

Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Evaluate the accuracy of a 23-gene expression signature in differentiating benign nevi from melanoma by comparing test results with clinical outcomes. Seven dermatopathologists blinded to gene expression test results and clinical outcomes examined 181 lesions to identify diagnostically uncertain cases. Participants independently recorded diagnoses and responses to questions quantifying diagnostic certainty. Test accuracy was determined through comparison with clinical outcomes (sensitivity and percent negative agreement). Overall, 125 cases fulfilled criteria for diagnostic uncertainty (69.1%; 95% CI: 61.8-75.7%). Test sensitivity and percent negative agreement in these cases were 90.4% (95% CI: 79.0-96.8%) and 95.5% (95% CI: 87.3-99.1%), respectively. The 23-gene expression signature has high diagnostic accuracy in diagnostically uncertain cases when evaluated against clinical outcomes.
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http://dx.doi.org/10.2217/pme-2020-0048DOI Listing
September 2020

Prognostic significance of acral lentiginous histologic type in T1 melanoma.

Mod Pathol 2021 03 5;34(3):572-583. Epub 2020 Aug 5.

Department of Pathology, Dermatopathology Section, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Acral lentiginous melanoma (ALM) is a rare type of cutaneous melanoma with a poor prognosis. It is unclear whether the poor outcome of ALM is due to its inherent disease characteristics or advanced stage at initial diagnosis. To address this question, we retrospectively analyzed the clinicopathologic factors of 828 thin (T1; Breslow thickness ≤1.0 mm) melanomas [129 (15.6%) ALMs and 699 (84.4%) non-ALMs] and their nodal and distance metastases and local recurrence rates and determined their relationship with the disease-specific (DSS), overall (OS), and recurrence-free survivals (RFS) at the pathologic stages T1, T1a, and T1b with a median follow-up time of 84.5 months. With the exception of OS at T1b stage, ALM patients showed significantly lower 5- and 10-year DSS, OS, and RFS rates at every pathologic stage when compared with non-ALM. In multivariable analysis, ALM histologic type, SLN positivity, age, and the use of systemic therapy were detected as independent poor prognostic factors associated with significantly lower survival rates. ALM histologic type was associated with lower DSS and OS rates at T1 and T1a stages and lower RFS rates at T1b stage. SLN positivity was associated with lower DSS, OS, and RFS rates at T1, T1a, and T1b stages. Age was associated with lower OS rates at T1 and T1b stages. Whereas the use of systemic therapy was associated with lower DSS rates at T1a stage and RFS rates at T1b stage. In addition, the ALM group showed significantly older median age patients and higher rates of female sex, Hispanic ethnicity, nevoid cytology, non-brisk tumor-infiltrating lymphocytes, nodal metastasis, and local recurrence at every pathologic stage of thin melanoma. Our findings suggest that ALM is inherently more aggressive than other types of cutaneous melanoma. This information may be useful for prognostic stratification of patients with thin melanomas, especially to help guide the clinical decision-making for SLN biopsy and patients entering clinical trials.
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http://dx.doi.org/10.1038/s41379-020-0641-xDOI Listing
March 2021

Correlative study of epigenetic regulation of tumor microenvironment in spindle cell melanomas and cutaneous malignant peripheral nerve sheath tumors.

Sci Rep 2020 08 3;10(1):12996. Epub 2020 Aug 3.

Department of Pathology, NYU Langone Health, NYU Grossman School of Medicine, 550 First Ave, New York, NY, 10016, USA.

The tumor microenvironment (TME) plays critical roles in tumor growth and progression, however key regulators of gene expression in the TME of cutaneous malignant peripheral nerve sheath tumor (C-MPNST) and spindle cell melanoma (SCM) have not been well elucidated. Herein, we investigate the epigenetic regulation of promoters and gene bodies and their effect on the TME composition of C-MPNSTs and SCMs. A cohort of 30 patients was analyzed using differential gene expression (DGE) and gene set enrichment analysis (GSEA) using the Nanostring platform. Methylation analysis was carried out utilizing an Infinium Methylation EPIC array targeting 866,562 methylation site (CpG) islands. DGE revealed overexpression of genes related to mast cells in the TME of SCMs, and a predominance of exhausted CD8 T cells and macrophages in the TME of C-MPNSTs. Interestingly, we further observed promoter hypermethylation in key overexpressed genes and corresponding gene body hypomethylation. Analysis using ENCODE ChIP-sequencing data identified CTCF as the common transcription factor at the site of the hypomethylated probe. These findings support that the TME composition of C-MPNSTs and SCMs is at least partially independent on promoter methylation status, suggesting a possible relationship between gene body enhancers and expression of key TME genes in both entities.
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http://dx.doi.org/10.1038/s41598-020-69787-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398924PMC
August 2020

Social Media Engagement at Academic Conferences: Report of the Association of Pathology Chairs 2018 and 2019 Annual Meeting Social Media Committee.

Acad Pathol 2020 Jan-Dec;7:2374289520934019. Epub 2020 Jul 17.

Association of Pathology Chairs, Wilmington, DE, USA.

The use of social media at academic conferences is expanding, and platforms such as Twitter are used to share meeting content with the world. Pathology conferences are no exception, and recently, pathology organizations have promoted social media as a way to enhance meeting exposure. A social media committee was formed ad hoc to implement strategies to enhance social media involvement and coverage at the 2018 and 2019 annual meetings of the Association of Pathology Chairs. This organized approach resulted in an 11-fold increase in social media engagement compared to the year prior to committee formation (2017). In this article, the social media committee reviews the strategies that were employed and the resultant outcome data. In addition, we categorize tweets by topic to identify the topics of greatest interest to meeting participants, and we discuss the differences between Twitter and other social media platforms. Lastly, we review the existing literature on this topic from 23 medical specialties and health care fields.
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http://dx.doi.org/10.1177/2374289520934019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370333PMC
July 2020

Langerhans cell sarcoma involving skin and showing epidermotropism: A comprehensive review.

J Cutan Pathol 2021 Apr 7;48(4):547-557. Epub 2020 Sep 7.

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

Langerhans cell sarcoma (LCS) is rare and aggressive; patients have an overall survival rate of less than 50%. We present a 62-year-old man with a history of superficial spreading melanoma of the upper back with sentinel lymph node metastasis, Langerhans cell histiocytosis, and LCS. The patient presented with erythematous papules and scaly areas on his face, neck, arms, chest, abdomen, and legs. A skin biopsy revealed a proliferation of large neoplastic cells involving the dermis and with epidermotropism. These cells had atypical bean-shaped nuclei, with ample cytoplasm and abundant mitotic figures including atypical forms. Immunohistochemical studies showed the tumor to be diffusely positive for CD1a, S100 protein, and langerin (CD207) and negative for melanocytic markers. Some tumor cells were positive for cyclin D1. A diagnosis of LCS involving the skin was established. The present study is a very unusual case of LCS showing epidermotropism. The patient's history of metastatic melanoma posed additional challenges for diagnosis, underlying the need of immunophenotyping in these cases. Consensus for optimal standard therapy has not been established in LCS, and thus, early recognition is important since these neoplasms tend to recur and metastasize. LCS in skin is discussed and published cases are comprehensively reviewed.
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http://dx.doi.org/10.1111/cup.13803DOI Listing
April 2021

Immune Checkpoint Inhibitor Therapy as an Eye-Preserving Treatment for Locally Advanced Conjunctival Melanoma.

Ophthalmic Plast Reconstr Surg 2021 Jan-Feb 01;37(1):e9-e13

Orbital Oncology and Ophthalmic Plastic Surgery, Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston.

The authors present 2 patients with locally advanced conjunctival melanoma for whom definitive surgery would mean an orbital exenteration with its associated inherent total visual loss and major facial disfigurement. Instead both patients were treated with immune checkpoint inhibitor therapy. In 1 patient neoadjuvant pembrolizumab was used for approximately 12 months and the patient experienced near-total clinical resolution of the conjunctival melanoma. Multiple surgical biopsies of very small residual pigmentation showed pigmented macrophages and a complete pathologic response. In the second patient who presented with a locally advanced and metastatic conjunctival melanoma, significant shrinkage of conjunctival mass was observed after treatment with a combination of ipilimumab and nivolumab for 5 months, and this allowed preservation of the eye and ocular function.
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http://dx.doi.org/10.1097/IOP.0000000000001700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744319PMC
April 2021

Unusual Presentations of Primary and Metastatic Adenoid Cystic Carcinoma Involving the Skin.

Am J Dermatopathol 2020 Dec;42(12):967-971

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

Adenoid cystic carcinoma (ACC) is most commonly seen in the salivary glands but may occur at other sites. Primary or metastatic involvement of the skin is unusual. We report 2 cases of ACC with unusual presentation. In the first case, a 55-year-old woman presented with a cutaneous lesion on the right shin, and final pathology showed ACC. An extracutaneous origin was excluded by clinical and imaging studies. In the second case, a 49-year-old woman presented with a nodule on the breast, and biopsy confirmed high-grade ACC (>30% solid areas). She underwent lumpectomy and subsequent mastectomy after recurrence. Sixteen months after the initial diagnosis of ACC of the breast, distant metastases at multiple sites, including the skin, were identified. This report will increase awareness of these rare presentations of cutaneous ACC and allow correct diagnosis and appropriate management of such cases.
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http://dx.doi.org/10.1097/DAD.0000000000001730DOI Listing
December 2020

Cutaneous adnexal carcinosarcoma: Immunohistochemical and molecular evidence of epithelial mesenchymal transition.

J Cutan Pathol 2021 Apr 14;48(4):526-534. Epub 2020 Sep 14.

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

Cutaneous carcinosarcomas are rare biphenotypic tumors that simultaneously show epithelial and mesenchymal differentiation. The most common carcinomatous components in skin carcinosarcomas are basal cell carcinoma and squamous cell carcinoma; adnexal carcinomas are rarely encountered. We report a case of an adnexal carcinoma with ductal and squamous differentiation and spindle cell component, which is interpreted as carcinosarcoma. Loss of immunohistochemical expression of E-cadherin and β-catenin detected in the sarcomatous component suggested epithelial mesenchymal transition (EMT). RNA sequencing analysis identified several gene mutations and alterations such as translocations and upregulations/downregulations, either shared by the two components of the tumor or differentially present in the carcinoma or the sarcoma parts. Thus, mutations in genes, such as TP53, were found in both components of the tumor while mutations in PDGFRA and RB1 (a pathogenic missense mutation) were exclusively present in the sarcomatous areas, further supporting EMT. EMT is a dynamic process by which tumors acquire mesenchymal phenotype while simultaneously losing epithelial properties. Although the pathways involved in EMT have been extensively studied, this phenomenon still needs to be investigated in cutaneous tumors of adnexal origin for a better understanding of their pathogenesis. These molecular changes may represent promising targets for personalized therapies.
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http://dx.doi.org/10.1111/cup.13782DOI Listing
April 2021

TERT amplification but not activation of canonical Wnt/β-catenin pathway is involved in acral lentiginous melanoma progression to metastasis.

Mod Pathol 2020 10 13;33(10):2067-2074. Epub 2020 May 13.

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

Acral lentiginous melanoma (ALM) is a rare tumor that occurs on non-sun exposed skin areas of the hands and feet. Reports suggest that ALM exhibits poor prognosis, although mechanisms driving this remain poorly understood. Alterations in TERT and the Wnt/β-catenin (Wnt) pathway have been suggested to correlate with prognosis of ALM. Thus, immunohistochemical expression of β-catenin and LEF1 along with TERT amplification by FISH was investigated in 34 primary ALMs, 20 metastatic ALMs, 10 primary non-ALMs, and 15 acral nevi. Foot/toe was the most common primary tumor location (85%) for ALM. TERT amplification was detected in 6 of 28 (21.4%) primary ALM, 2 of 8 (25%) primary non-ALM, and 8 of 18 (44.4%) metastatic ALM, the latter showing significantly higher frequency compared with primary melanomas (P = 0.043). Most metastatic ALMs positive for TERT amplification lacked BRAF V600E (87.5%). Cytoplasmic and nonnuclear expression of β-catenin was variably detected in all cases. Metastatic ALM revealed lower expression of β-catenin compared with primary ALM (P = 0.017). No differences in LEF1 expression were detected among the groups; however, acral nevi showed decreased labeling with dermal descent, in contrast to melanoma. No molecular-genetic alteration correlated with prognosis. TERT amplification by FISH is a frequent finding in primary ALM and appears to increase in metastatic tumors, suggesting a role in tumor progression to metastasis. Although TERT amplification has been reported to be infrequent in primary non-ALM, it showed comparable frequency with ALM in our series. Our immunohistochemical findings are not fully supportive of activation of either canonical or noncanonical Wnt cascades in ALM. TERT amplification by FISH and LEF1 immunohistochemistry may help in the differential diagnosis between primary ALM and acral nevus. TERT amplification appears to be a promising target for therapy in patients with metastatic ALM.
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http://dx.doi.org/10.1038/s41379-020-0565-5DOI Listing
October 2020

Hypertrophic lichenoid dermatitis immune-related adverse event during combined immune checkpoint and exportin inhibitor therapy: A diagnostic pitfall for superficially invasive squamous cell carcinoma.

J Cutan Pathol 2020 Oct 10;47(10):954-959. Epub 2020 Jun 10.

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

Immune checkpoint inhibitors (ICIs) for cancer treatment have revolutionized the field of medicine. However, an unintended but frequent consequence of ICI therapy is the development of cutaneous immune-related adverse events (irAEs), such as lichenoid dermatitis irAEs (LD-irAEs). The hypertrophic variant of LD-irAE may be a diagnostic challenge since it can mimic superficially invasive squamous cell carcinoma (SCC). A 79-year-old woman with metastatic melanoma who began treatment with an ICI-pembrolizumab-plus exportin-1 (XPO1) inhibitor presented after 1 month of therapy with symmetrical violaceous papules coalescing into plaques and with two nodules of the bilateral dorsal hands. Biopsy of the nodules revealed an actinic keratosis and atypical epidermal proliferation concerning for SCC. However, in the ensuing 3 weeks, the patient developed multiple new erythematous, violaceous, and scaly macules and papules, some coalescing into plaques on the extremities. Biopsies of these lesions revealed exuberant irregular epidermal hyperplasia with hypermaturation and lichenoid infiltrate concentrated at the base of the elongated, broadened rete ridges, consistent with hypertrophic LD-irAE. Treatment included topical fluocinonide ointment, intralesional triamcinolone injections and oral acitretin. Distinguishing hypertrophic LD-irAE and SCC can be challenging since both entities share histopathologic features; thus, correlation with clinical presentation is essential for diagnosis and optimal patient management.
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http://dx.doi.org/10.1111/cup.13739DOI Listing
October 2020

BAP-1 Expression Status by Immunohistochemistry in Cellular Blue Nevus and Blue Nevus-like Melanoma.

Am J Dermatopathol 2020 May;42(5):313-321

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

The family of blue nevi includes the common blue nevus (BN), cellular blue nevus (CBN), and atypical BN, while melanomas with BN-like morphology can either arise in association with a blue nevus (MABN) or in the de novo setting mimicking cellular blue nevus (MMCBN). Recent molecular and immunohistochemical studies have demonstrated loss of BAP-1 in MABN/MMCBN but not in BN/CBN, suggesting that loss of BAP-1 correlates with a malignant phenotype in these lesions. In this study, we applied anti-BAP-1 antibodies to a series of CBN/BN (n = 11) and MABN/MMCBN (n = 4). Nuclear BAP-1 expression was detected in the majority of CBN/BN (n = 10/11) but was lost in 1 case. Most cases of MABN/MMCBN showed loss of nuclear BAP-1 expression (n = 3/4), with one case of MMCBN showing preserved BAP-1 expression. Demonstration of BAP-1 loss in a single case of CBN and preservation of BAP-1 expression in 1 case of MMCBN may indicate that detection of alterations in BAP-1 protein expression by immunohistochemistry may not be a completely reliable biomarker for the distinction of BN/CBN from MABN/MMCBN. Further investigation of the significance of BAP-1 loss/preservation in BN-like tumors is warranted.
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http://dx.doi.org/10.1097/DAD.0000000000001551DOI Listing
May 2020