Publications by authors named "Marier Hernandez-Perez"

11 Publications

  • Page 1 of 1

Multiple Erythematous Papules on the Toes: Challenge.

Am J Dermatopathol 2021 Aug;43(8):e93-e94

Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA; and.

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http://dx.doi.org/10.1097/DAD.0000000000001805DOI Listing
August 2021

Multiple Erythematous Papules on the Toes: Answer.

Am J Dermatopathol 2021 Aug;43(8):599-600

Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA; and.

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http://dx.doi.org/10.1097/DAD.0000000000001806DOI Listing
August 2021

Primary cutaneous follicle center lymphoma in a 16-year-old girl.

J Cutan Pathol 2021 May 13;48(5):663-668. Epub 2021 Jan 13.

Department of Pathology, University of Virginia, Charlottesville, Virginia, USA.

In the pediatric and adolescent age group, primary cutaneous lymphomas are rare, especially cutaneous B-cell lymphomas. According to the World Health Organization, the three main subtypes of primary cutaneous B-cell lymphomas are primary cutaneous marginal zone B-cell lymphoma (PCMZL), primary cutaneous follicle center lymphoma (PCFCL), and primary cutaneous diffuse large B-cell lymphoma, leg type. We present an extraordinary case of PCFCL arising in a 16-year-old female, only the sixth case of PCFCL to be reported in the literature in a patient less than 20 years old. Although PCMZL was considered in this case, the finding of lambda light chain restriction in the BCL-6 and CD10 positive population of lymphocytes established the diagnosis of primary cutaneous follicle center lymphoma. Not many data currently exist on the prognosis of PCFCL in young individuals, but adult PCFCL has a good prognosis with an indolent course and 5-year survival rates over 95%. Because of its uncommon manifestation in young patients, the diagnosis of PCFCL is often delayed or missed. This case is presented to raise awareness of PCFCL in the pediatric/ adolescent population and to contribute to the ongoing research of this condition.
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http://dx.doi.org/10.1111/cup.13939DOI Listing
May 2021

Atypical ALK-positive Spitz tumors with 9p21 homozygous deletion: Report of two cases and review of the literature.

J Cutan Pathol 2018 Feb 28;45(2):136-140. Epub 2017 Nov 28.

Miraca Life Sciences, Newton, Massachusetts.

ALK rearrangements occur in up to 10% of spitzoid melanocytic neoplasms. No reported cases have shown homozygous deletion of 9p21 (CDKN2A) or gains of 6p25 (RREB1) or 11q13 (CCND1), which have been associated with aggressive clinical behavior. Here we report 2 unique cases. Case 1 occurred in a 9-year-old male with a 14-mm nodule on the anterior left thigh. Biopsy revealed an ALK-positive Spitz tumor containing an irregular nodule of densely packed melanocytes with increased mitoses and loss of p16 immunoreactivity. FISH analysis showed homozygous deletion of 9p21 and gain of 6p25. Sentinel lymph node biopsy revealed small subcapsular foci of tumor. Case 2 occurred in a 7-year-old female with a 12-mm nodule on the anterior right ankle. Biopsy revealed an ALK-positive Spitz tumor containing an expansile nodule of pleomorphic epithelioid melanocytes with numerous mitoses and loss of p16 immunoreactivity. By FISH, the nodule showed homozygous deletion of 9p21 and gains of 6p25 and 11q13. Our cases show the transformation of tumors produced by an activating kinase fusion gene (ALK) through secondary genetic changes including loss of tumor suppressor activity (CDKN2A). Long-term follow up will be important to further define the behavior of these unique Spitz tumors.
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http://dx.doi.org/10.1111/cup.13057DOI Listing
February 2018

Tumoral PD-L1 expression in desmoplastic melanoma is associated with depth of invasion, tumor-infiltrating CD8 cytotoxic lymphocytes and the mixed cytomorphological variant.

Mod Pathol 2017 03 13;30(3):357-369. Epub 2017 Jan 13.

Dermatopathology Section, Department of Pathology and Laboratory Medicine (113), VA Integrated Service Networks (VISN1), West Roxbury, MA, USA.

Recently, patients with metastatic desmoplastic melanoma (DM) have been shown to respond more favorably to anti-PD1/PD-L1 therapy than other melanoma subtypes. Given this, we evaluated PD-L1/2 expression in primary DM samples and correlated these with subtype, CD8+ lymphocyte status, histopathological prognosticators, and select genetic alterations. Eighty-six (36 mixed DM, 50 pure DM) archival annotated samples met inclusion criteria and were immunohistochemically semiquantitatively evaluated. Per established criteria, for PD-L1/L2, cases with ⩾5% tumoral expression, and for CD8, cases with a predominantly peri/intratumoral CD8+ infiltrate were scored positive. Univariate analysis (chi-square and Wilcoxon) identified potential confounders and a nested case-control study was accomplished using multiple logistic regression. For PD-L1, 49% of cases were positive and 71% of cases with thickness >4 mm were positive; PD-L1 expression differed by median depth (3.29 mm, interquartile range=3.58 mm for PD-L1 positives vs 1.75 mm, interquartile range=2.04 mm for PD-L1 negatives, P=0.0002) and was linearly associated with increasing depth of invasion (P=0.0003). PD-L1-positive cases were more likely to display CD8+ lymphocytes (60 vs 28% P=0.0047).The presence of CD8+ lymphocytes correlated significantly with depth of invasion >1 mm (P=0.022). On multivariate analysis, PD-L1 was 6.14 × more likely to be expressed in mixed DM than pure DM (P=0.0131), CD8+ staining was 6.22 × more likely in PD-L1 positive cases than in PD-L1 negative (P=0.0118), and tumor depth was associated with greater odds of PD-L1 expression (OR=1.61, P=0.0181). PD-L2 expression was observed in 48% of cases but did not correlate with any variables. Correlation of tumoral PD-L1 with increased depth and CD8+ lymphocytes implicates the tumoral immune microenvironment with advancing disease in DM. Enhanced tumoral PD-L1 expression in the mixed cytomorphological variant provides an insight into the differential pathogenesis of the subtypes and suggests that these patients are likely better candidates for anti-PD/PD-L1 therapy.
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http://dx.doi.org/10.1038/modpathol.2016.210DOI Listing
March 2017

Frequency of telomerase reverse transcripter promoter mutations in desmoplastic melanoma subtypes: analyses of 76 cases.

Melanoma Res 2016 08;26(4):361-6

aDepartment of Pathology, Boston University of Medicine bBoston University School of Public Health and Ragon Institute of MGH, MIT and Harvard cDepartment of Pathology, Massachusetts General Hospital, Boston dMiraca Life Sciences, Newton Upper Falls eDepartment of Pathology, University of Massachusetts Medical School, Worcester fDermatopathology Section, VA Integrated Systems Network (VISN1), Department of Pathology and Laboratory Medicine, West Roxbury, Massachusetts gCarver College of Medicine, University of Iowa, Iowa City, Iowa hDepartment of Pathology and Dermatology, Icahn School of Medicine Mount Sinai, New York, New York iAurora Diagnostics GPA Laboratories, Greensboro, North Carolina, USA jDepartment of Pathology, Western General Hospital, Edinburgh, Scotland, UK.

Estimates of the frequency of telomerase reverse transcripter (TERT) mutations in desmoplastic melanoma (DM) are limited. DM is categorized into subtypes, pure and mixed, differing in prognosis, suggesting genetic heterogeneity. Given this, our aims were to determine the incidence of TERT promoter mutations in DM subtypes and to evaluate its relationship with established histopathologic prognosticators, BRAF and RETp status, and neurofibromin protein expression. Of the archival annotated samples retrieved, 76 cases of DM (48 pure and 28 mixed) fulfilled the criteria for inclusion. PCR amplification of the TERT promoter region was performed on DNA extracted from formalin-fixed paraffin-embedded tissue using primers5'-GCCGATTCGACCTCTCTCC-3' (forward) and 5'-CAGCGCTGCCTGAAACTC-3' (reverse). For each case, appropriate C>T mutations were identified on the electropherograms. Univariate analysis using χ-test was carried out to identify potential confounders; a nested case-control study of demographic, clinical, histopathological, and genetic determinants was carried out using multiple logistic regression. Significant differences in TERT promoter mutation frequencies were noted in the subtypes (mixed vs. pure; 15/28, 54% vs. 11/48, 23%, respectively, P=0.0066). After adjusting for potential confounding, multivariate analyses indicated a three-fold increase in the odds of the TERT mutation for those with the mixed subtype compared with the pure subtype (P=0.04, adjusted odds ratio =3.32). No other significant associations were noted (sex/junctional component/Breslow depth/ulceration/mitoses/host response/RETp, BRAF status, and neurofibromin protein expression). Our findings, the largest to date investigating TERT promoter mutations in DM, support the hypothesis that the subtypes have distinct genetic drivers and underscore the relevance of telomere integrity in the etiopathogenesis of the mixed variant.
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http://dx.doi.org/10.1097/CMR.0000000000000272DOI Listing
August 2016

Neurofibromin protein loss in desmoplastic melanoma subtypes: implicating NF1 allelic loss as a distinct genetic driver?

Hum Pathol 2016 07 9;53:82-90. Epub 2016 Mar 9.

Dermatopathology Section, Department of Pathology and Laboratory Medicine, VA Consolidated Laboratories, West Roxbury, MA 02132. Electronic address:

Loss of the NF1 allele, coding for the protein neurofibromin, and polymorphism in the proto-oncogene RET (RETp) are purportedly common in desmoplastic melanoma (DM). DM is categorized into pure (PDM) and mixed (MDM) subtypes, which differ in prognosis. Most NF1 mutations result in a truncated/absent protein, making immunohistochemical screening for neurofibromin an ideal surrogate for NF1 allelic loss. Using antineurofibromin, our aims were to ascertain the incidence of neurofibromin loss in DM subtypes and to evaluate the relationship with RET, perineural invasion (PNI) and established histopathologic prognosticators. A total of 78 archival samples of DM met criteria for inclusion (54 cases of non-DM serving as controls). Immunohistochemistry was performed for neurofibromin, whereas direct DNA sequencing was used for RETp and BRAF mutation status. Statistical analyses included χ(2) test as well as Fisher exact test. Neurofibromin loss was more common in DM than non-DM (69% versus 54%; P=.02). In DM, significant differences in neurofibromin loss were noted in the following: non-head and neck versus head and neck biopsy site (88% versus 55%) and PDM versus MDM variants (80% versus 56%). No significant associations were noted with sex, presence of a junctional component, Breslow depth, ulceration, mitoses, host response, RETp, BRAF status, or PNI. RETp was marginally associated with PNI-positive DM versus PNI-negative DM (36 versus 18%; P=.08). Our findings, the largest to date investigating neurofibromin in DM, validate the incidence of NF1 mutations/allelic loss in DM and suggest that the DM subtypes have distinct genetic drivers.
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http://dx.doi.org/10.1016/j.humpath.2016.02.012DOI Listing
July 2016

Matrix metalloproteinases in health and disease: insights from dermatopathology.

Am J Dermatopathol 2012 Aug;34(6):565-79

Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA 02118, USA.

Matrix metalloproteinases, a group of over 26 zinc-dependent enzymes, share a similar structure to each other and functionally are capable of degrading almost every component of the extracellular matrix. They are essential to normal development during embryogenesis and extracellular matrix remodeling and, given this, understandably enough have been implicated in multiple pathologic processes that encompass the inflammatory and neoplastic spectrum of disease. This review attempts to define roles of matrix metalloproteinases of relevance in normal skin and to elucidate their roles in inflammatory dermatoses and benign and malignant neoplasms.
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http://dx.doi.org/10.1097/DAD.0b013e31821e8744DOI Listing
August 2012

Expression of gelatinases (MMP-2, MMP-9) and gelatinase activator (MMP-14) in actinic keratosis and in in situ and invasive squamous cell carcinoma.

Am J Dermatopathol 2012 Oct;34(7):723-8

Pathology Department and Laboratory Medicine, Boston University School of Medicine, Boston, MA 02118, USA.

Given the established role of matrix metalloproteinases (MMPs) in physiological processes in the skin, we investigated the expression of MMP-2, MMP-9, and MMP-14 to evaluate their role in the grading and development of atypical epithelial lesions. Immunohistochemistry was performed using antibodies against these MMPs in actinic keratosis (AK; n = 24), squamous cell carcinoma (SCC) in situ (SCCIS; n = 27), SCC well differentiated (SCCWD; n = 28), and SCC moderately to poorly differentiated (SCCMPD; n = 20). Tumoral and stromal expression was assessed by intensity (SI) and percentage positivity (PC). The mean of the total score, calculated by adding intensity and percentage positivity, was used for statistical analyses. In AK, SCCIS, SCCWD, and SCCMPD, mean tumoral MMP-2 expression was 3.33, 4.07, 4.46, and 3.40, respectively (P = NS for all) and stromal expression was 1.42, 3.26, 3.07, and 1.55 respectively (P < 0.05 for AK vs. SCCIS/SCCWD and SCCMPD vs. SCCIS/SCCWD); mean tumoral MMP-9 expression was 4.33, 4.11, 4.46, and 3.35, respectively, and stromal expression was 4.29, 4.41, 4.75, and 4.60, respectively (P = NS for all) and, mean tumoral MMP-14 expression was 1.58, 2.41, 0.32, and 0.35, respectively (P < 0.05 AK vs. SCCWD and SCCIS vs. SCCWD/SCCMPD) and stromal expression was 3.04, 3.52, 0.46, and 0.60, respectively (P < 0.05 for AK vs. SCCWD/SCCMPD). Only MMP-14 showed a statistically significant linear trend with decreasing values for tumoral and stromal expression with invasion suggesting that it might be of use as a prognosticator. Enhanced stromal MMP-2 expression in SCCIS and SCCWD relative to AK suggests that it may be of relevance to disease progression.
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http://dx.doi.org/10.1097/DAD.0b013e31824b1ddfDOI Listing
October 2012

Cutaneous lepidopterism: dermatitis from contact with moths of Hylesia metabus (Cramer 1775) (Lepidoptera: Saturniidae), the causative agent of caripito itch.

Int J Dermatol 2011 May;50(5):535-41

Department of Pathology and Laboratory Medicine, St Luke's-Roosevelt Hospital Center, New York, NY, USA.

Background: Lepidopterism derived from contact with arthropods and/or their products can result in adverse reactions that vary in severity from mild irritation to severe reactions including anaphylactic shock and death. Lepidopterism includes cutaneous and/or mucosal manifestations, systemic symptoms, or both mucocutaneous and systemic manifestations.

Objective:   Epidemic outbreaks of dermatitis due to Hylesia sp. have been recorded in several countries of Latin America. The impact of climatic changes occurring presently on migrational and reproductive cycles of Hylesia metabus is also discussed in this study.

Materials And Methods: In Venezuela, swarms of migrating H. metabus moths are historically recognized as the causative agents of "Caripito itch," a disease that has become an important public health problem.

Results: In this review, we present a series of four case reports reflecting the wide clinical pleomorphism exhibited in lepidopterism by H. metabus.

Conclusion: Although dermatitis caused by these moths is usually resistant to all therapeutic treatment, individualization of therapy based on symptoms led to successful treatment in all four cases.
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http://dx.doi.org/10.1111/j.1365-4632.2010.04683.xDOI Listing
May 2011

Distinctive association of p16INK4a overexpression with penile intraepithelial neoplasia depicting warty and/or basaloid features: a study of 141 cases evaluating a new nomenclature.

Am J Surg Pathol 2010 Mar;34(3):385-92

Instituto de Patología e Investigación, Asunción, Paraguay.

From the pathogenic point of view, penile cancers may be grouped in human papillomavirus-related and unrelated tumors, each one of them with distinctive morphologic features. The former are predominantly composed of small, undifferentiated basaloid cells, with more or less prominent koilocytic changes, and the latter of keratinizing differentiated squamous cells. The same cellular types are observed in precancerous lesions. On the basis of these observations, we constructed a novel nomenclature for penile precancerous lesions and classified them as penile intraepithelial neoplasia (PeIN) of differentiated, warty, basaloid, and warty-basaloid types. The aim of this study was to test the usefulness of immunohistochemical p16 overexpression, considered as a surrogate for high-risk human papillomavirus infection, using this classification system. We pathologically evaluated 141 patients with PeIN, associated (123 cases) and unassociated (18 cases) with invasive cancer. Distribution of PeIN types was: differentiated, 72%; basaloid, 9%; warty-basaloid, 7%; warty, 4%; and mixed, 7%. There was a striking similarity in the morphology of in situ and invasive squamous cell carcinomas. Differentiated PeIN was commonly associated with usual, verrucous, papillary, and other low-grade keratinizing variants of squamous cell carcinoma whereas in basaloid and warty carcinomas the presence of in situ lesions with similar morphology was habitual. We evaluated p16 overexpression using a 4-tiered (0, 1, 2, and 3) pattern-based system. To properly distinguish differentiated PeIN from in situ lesions with warty and/or basaloid features only pattern 3, which requires full-thickness staining in all epithelial cells, was considered positive. Using this approach, there was a significant association of the negative patterns and differentiated PeIN and of the positive pattern and warty, basaloid, and warty-basaloid PeIN (P<0.0001). Basaloid variant had the strongest association. The sensitivity rate of p16 positivity for discriminating types of PeIN was of 82%, with a specificity of 100% and an accuracy of 95%. Lichen sclerosus was identified in 42 cases and their epithelial component was p16 negative in all cases. Although more studies are necessary to confirm these observations, p16 overexpression seems to be a useful tool for discriminating differentiated from warty, basaloid, and warty-basaloid PeIN.
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http://dx.doi.org/10.1097/PAS.0b013e3181cdad23DOI Listing
March 2010
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