Mai P Hoang

Harvard Medical School, Boston, Massachusetts, United States

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Publications (136)680.96 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Patients with heterozygous germline mutations in BRCA1-associated protein 1 (BAP1), a tumor suppressor gene, develop a tumor predisposition syndrome (OMIM 614327) with increased risk of uveal and cutaneous melanomas, cutaneous atypical and epithelioid melanocytic lesions, lung adenocarcinoma, clear cell renal cell carcinoma, and other tumors. Early recognition of this syndrome is of clinical importance. In addition, screening for BAP1 mutation, loss, and inactivation by performing BAP1 immunohistochemistry on cutaneous lesions would be a simple method for screening patients suspected of having germline BAP1 mutations. We investigated BAP1 expression in seven basal cell carcinomas (BCCs) in two patients with germline BAP1 mutation and a family history of uveal melanoma. Six lesions were from the head and neck region and one from the shoulder. Thirty-one sporadic BCCs were included as controls. All seven BCCs in the patients with germline BAP1 mutations exhibited loss of BAP1 nuclear staining, while 30 (97%) of 31 sporadic BCCs exhibited positive BAP1 nuclear staining. Loss of BAP1 expression could be associated with the development of BCC in patients with germline BAP1 mutations. These results suggest that BCC may be a component of the expanding category of tumors associated with this syndrome. Copyright© by the American Society for Clinical Pathology.
    American Journal of Clinical Pathology 06/2015; 143(6):901-4. DOI:10.1309/AJCPG8LFJC0DHDQT · 3.01 Impact Factor
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    ABSTRACT: Perineural invasion (PNI) in desmoplastic melanoma is associated with increased local recurrence and reduced disease-free survival. The biological mechanisms underlying PNI remain unclear although several lines of evidence implicate neurotrophins and their receptors. We investigated the expression of p75NGFR and TrkA, and the presence of functional RET polymorphism (RETp) as they relate to PNI in desmoplastic melanoma. In all, 43 cases of desmoplastic melanoma were immunohistochemically evaluated for TrkA and p75NGFR expression and RETp was detected by direct DNA sequencing. PNI was present in 67% of cases. On univariate analysis, p75NGFR was associated with PNI (expression detected in 79% of PNI-positive cases compared with 36% of PNI-negative cases, P = .005), increased Breslow depth (P = .007), and greater Clark level (P = .01). RETp was noted in 28% of cases but was not significantly associated with PNI (P = .27) or other histopathologic variables. TrkA expression was absent in all cases. PNI was associated with increased Breslow depth and Clark level (P = .01 and P = .009, respectively). Controlling for the association between p75NGFR and depth, p75NGFR remained associated with an increased propensity for PNI (odds ratio 4.68, P = .04). The sample size was limited. In desmoplastic melanoma, p75NGFR expression is significantly associated with PNI and a more locally aggressive phenotype. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
    Journal of the American Academy of Dermatology 03/2015; 45(5). DOI:10.1016/j.jaad.2015.01.026 · 5.00 Impact Factor
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    ABSTRACT: A 25-year-old man presented with oral ulcers and odynophagia. On examination, there were scattered pink papules and plaques on the trunk, thighs, and buttocks and multiple raised, erythematous nodules on both shins. A diagnostic procedure was performed.
    New England Journal of Medicine 02/2015; 372(9):864-72. DOI:10.1056/NEJMcpc1413303 · 54.42 Impact Factor
  • Circulation 02/2015; 131(5):514-5. DOI:10.1161/CIRCULATIONAHA.114.013086 · 14.95 Impact Factor
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    ABSTRACT: Importance Conclusive intraoperative pathologic confirmation of diffuse infiltrative glioma guides the decision to pursue definitive neurosurgical resection. Establishing the intraoperative diagnosis by histologic analysis can be difficult in low-cellularity infiltrative gliomas. Therefore, we developed a rapid and sensitive genotyping assay to detect somatic single-nucleotide variants in the telomerase reverse transcriptase (TERT) promoter and isocitrate dehydrogenase 1 (IDH1).Observations This assay was applied to tissue samples from 190 patients with diffuse gliomas, including archived fixed and frozen specimens and tissue obtained intraoperatively. Results demonstrated 96% sensitivity (95% CI, 90%-99%) and 100% specificity (95% CI, 95%-100%) for World Health Organization grades II and III gliomas. In a series of live cases, glioma-defining mutations could be identified within 60 minutes, which could facilitate the diagnosis in an intraoperative timeframe.Conclusions and Relevance The genotyping method described herein can establish the diagnosis of low-cellularity tumors like glioma and could be adapted to the point-of-care diagnosis of other lesions that are similarly defined by highly recurrent somatic mutations.
    01/2015; DOI:10.1001/jamaoncol.2015.0917
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    ABSTRACT: Hemangioblastomas consist of 10-20% neoplastic ¿stromal¿ cells within a vascular tumor cell mass of reactive pericytes, endothelium and lymphocytes. Familial cases of central nervous system hemangioblastoma uniformly result from mutations in the Von Hippel-Lindau (VHL) gene. In contrast, inactivation of VHL has been previously observed in only a minority of sporadic hemangioblastomas, suggesting an alternative genetic etiology. We performed deep-coverage DNA sequencing on 32 sporadic hemangioblastomas (whole exome discovery cohort n¿=¿10, validation n¿=¿22), followed by analysis of clonality, copy number alteration, and somatic mutation. We identified somatic mutation, loss of heterozygosity and/or deletion of VHL in 8 of 10 discovery cohort tumors. VHL inactivating events were ultimately detected in 78% (25/32) of cases. No other gene was significantly mutated. Overall, deep-coverage sequence analysis techniques uncovered VHL alterations within the neoplastic fraction of these tumors at higher frequencies than previously reported. Our findings support the central role of VHL inactivation in the molecular pathogenesis of both familial and sporadic hemangioblastomas.
    Acta Neuropathologica 12/2014; 2(1). DOI:10.1186/s40478-014-0167-x · 9.78 Impact Factor
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    ABSTRACT: Antibodies that recognize neo-epitopes in tumor cells are valuable tools in the evaluation of tissue biopsy or resection specimens. The VE1 antibody that recognizes the V600E-mutant BRAF protein is one such example. We have recently shown that the vast majority of papillary craniopharyngiomas-tumors that arise in the sellar or suprasellar regions of the brain-harbor BRAF V600E mutations. The VE1 antibody can be effective in discriminating papillary craniopharyngioma from adamantinomatous craniopharyngioma, which harbors mutations in CTNNB1 and not BRAF. While further characterizing the use of the VE1 antibody in the differential diagnosis of suprasellar lesions, we found that the VE1 antibody stains the epithelial cells lining Rathke's cleft cysts with very strong staining of the cilia of these cells. We used targeted sequencing to show that Rathke's cleft cysts do not harbor the BRAF V600E mutation. Moreover, we found that the VE1 antibody reacts strongly with cilia in various structures-the bronchial airways, the fallopian tubes, the nasopharynx, and the epididymis-as well as with the flagella of sperm. In addition, VE1 reacts strongly with the cilia of the ependymal lining of the brain and with the cilia-containing microlumens of ependymoma tumors. There is significant sequence homology between the synthetic peptide (amino acid 596-606 of BRAF V600E: GLATEKSRWSG) that was used to generate the VE1 antibody and regions of multiple axonemal dynein heavy chain proteins (eg, DNAH2, DNAH7, and DNAH12). These proteins are major components of the axonemes of cilia and flagella where they drive the sliding of microtubules. In ELISA assays, we show that the VE1 antibody recognizes epitopes from these proteins. A familiarity with the cross-reactivity of the VE1 antibody with epitopes of proteins in cilia is of value when evaluating tissues stained with this important clinical antibody.Modern Pathology advance online publication, 21 November 2014; doi:10.1038/modpathol.2014.150.
    Modern Pathology 11/2014; 28(4). DOI:10.1038/modpathol.2014.150 · 6.36 Impact Factor
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    ABSTRACT: BAP1 (BRCA1-Associated Protein 1) is a tumor suppressor gene whose mutations have recently been reported to increase susceptibility for the development of uveal melanoma, cutaneous atypical and epithelioid melanocytic lesions, clear cell renal cell carcinoma and other tumors. Screening for BAP1 mutation/loss/inactivation and BRAFV600E mutation can be done by immunohistochemistry. We investigated BAP1 and BRAFV600E expression in 193 sporadic melanocytic lesions (11 dermal nevi, 20 congenital nevi, 40 primary and non-desmoplastic melanomas, 40 desmoplastic melanomas, 23 metastatic melanomas, 17 Spitz nevi, 19 atypical Spitz nevi, 8 atypical Spitz tumors, 14 proliferative nodules arising in congenital nevi, 1 nevus during pregnancy), and 30 melanocytic lesions from 3 patients with family history of uveal melanoma and BAP1 germline mutation. Most sporadic melanocytic lesions exhibited positive BAP1 nuclear staining except for 1 proliferative nodule arising in congenital nevus; 1 desmoplastic, 1 nevoid and 2 metastatic melanomas. BRAFV600E positivity was demonstrated in 80% of dermal, 5% of congenital, 6% of Spitz, and 5.5% of atypical Spitz nevi; 29% of proliferative nodules arising in congenital nevi; 24% of primary and non-desmoplastic and 35% of metastatic melanomas. Combined BAP1 loss and BRAFV600E staining was seen in 67% of BAP1 tumor syndrome-associated lesions and in none of the sporadic melanocytic proliferations including Spitz and atypical Spitz nevi and atypical Spitz tumors, with the exception of 1 primary melanoma. The combined BAP1-BRAFV600E + immunoprofile appears to be a constant feature of BAP1 tumor syndrome-associated melanocytic lesions, and the designation of Spitz nevi or variants thereof appears to be inaccurate for this group of lesions.
    Human pathology 11/2014; 46(2). DOI:10.1016/j.humpath.2014.10.015 · 2.81 Impact Factor
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    ABSTRACT: The management of dysplastic nevi (DN) is a highly debated and controversial topic within the dermatology community. Clinicians agree that margin-positive severely DN should be removed with a surgical margin, however, there is disagreement surrounding the appropriate management of margin-positive mildly and moderately DN.
    Journal of the American Academy of Dermatology 09/2014; DOI:10.1016/j.jaad.2014.08.025 · 5.00 Impact Factor
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    ABSTRACT: : Currently, urogenital complaints are among the most common problems encountered by family practitioners, gynecologists, and dermatologists. In response to the intricacy of vulvar disorders, the International Society for the Study of Vulvovaginal Disease was created to facilitate the exchange between clinicians and pathologists involved in the care of these patients. Recent classifications for inflammatory disorders and intraepithelial neoplasm have been proposed. In addition, vulvar skin biopsies are the most common source of intradepartmental consultation during dermatopathology sign-out. The purpose of this article is to review the various inflammatory dermatoses of the vulva and to update readers with new advances regarding these entities.
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    ABSTRACT: Objectives: The VE1 monoclonal antibody was developed to recognize the V600E mutation in BRAF, which is found in various tumors. Methods: We report that the VE1 antibody stains normal anterior pituitary gland and adrenal cortex, which lack detectable BRAF V600E mutations. Results: Staining with the VE1 antibody was seen in the adenohypophysis and correlated well with adrenocorticotropic hormone (ACTH) positive cells. ACTH-positive cells were typically most concentrated in the central mucoid wedge and pars intermedia, and VE1 staining was strong in these regions. Moreover, VE1 staining was seen in ACTH-expressing pituitary adenomas without detectable BRAF mutations. VE1 staining of the adrenal cortex was also significant, with the strongest staining seen in the inner segment of the zona fasciculata. Parathyroid glands, pancreatic islets, or parafollicular C cells in the thyroid showed no VE1 staining. Conclusions: Overall, VE1 staining of endocrine tissues strongly suggests limitations on the use of this antibody for the detection of BRAF mutations.
    American Journal of Clinical Pathology 06/2014; 141(6):811-5. DOI:10.1309/AJCP37TLZLTUAOJL · 3.01 Impact Factor
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    ABSTRACT: The histopathologic distinction between primary adnexal carcinomas and metastatic adenocarcinoma to the skin from sites such as the breast, lung, and others often presents a diagnostic dilemma. Current markers of diagnostic utility include p63 and cytokeratin 5/6; however, their expression has been demonstrated in 11%-22% and 27% of cutaneous metastases, respectively. Furthermore, the immunoreactivity of p40 and GATA3 in various cutaneous adnexal carcinomas has not been previously reported. In the present study, we compared the expression of p40, p63, cytokeratin 5/6, and GATA3 in a total of 143 cases, including 67 primary adnexal carcinomas and 76 cutaneous metastases. p40, p63, cytokeratin 5/6, and GATA3 expression was observed in 80%, 84%, 86% and 47% of primary adnexal carcinoma, respectively; and in 8%, 17%, 26% and 40% of cutaneous metastases, respectively. Chi-square analysis revealed statistically significant p-values (<0.0001) for p40, p63, and cytokeratin 5/6 in distinguishing primary adnexal carcinoma from cutaneous metastases. In summary, while p63 and cytokeratin 5/6 have similar sensitivity (84% and 86%, respectively) in detecting primary adnexal carcinomas, p40 appeared to be the most specific marker (92%) with the best positive predictive value (90%). Since breast and lung are the most common sites of origin for cutaneous metastases, p40 is the best distinguishing marker in these settings. None of the four studied markers (p40, p63, cytokeratin 5/6, and GATA3) are helpful in distinguishing between primary adnexal carcinomas from cutaneous metastases of salivary gland or bladder malignancies.
    Human pathology 05/2014; 45(5). DOI:10.1016/j.humpath.2014.01.006 · 2.81 Impact Factor
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    ABSTRACT: Melanoma is an invasive malignancy with a high frequency of blood-borne metastases, but circulating tumor cells (CTCs) have not been readily isolated. We adapted microfluidic CTC capture to a tamoxifen-driven B-RAF/PTEN mouse melanoma model. CTCs were detected in all tumor-bearing mice and rapidly declined after B-RAF inhibitor treatment. CTCs were shed early from localized tumors, and a short course of B-RAF inhibition following surgical resection was sufficient to dramatically suppress distant metastases. The large number of CTCs in melanoma-bearing mice enabled a comparison of RNA-sequencing profiles with matched primary tumors. A mouse melanoma CTC-derived signature correlated with invasiveness and cellular motility in human melanoma. CTCs were detected in smaller numbers in patients with metastatic melanoma and declined with successful B-RAF-targeted therapy. Together, the capture and molecular characterization of CTCs provide insight into the hematogenous spread of melanoma.
    Cell Reports 04/2014; 7(3). DOI:10.1016/j.celrep.2014.03.039 · 7.21 Impact Factor
  • Journal of Clinical Oncology 02/2014; 32(9). DOI:10.1200/JCO.2013.52.3571 · 17.88 Impact Factor
  • 01/2014; 150(5). DOI:10.1001/jamadermatol.2013.6892
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    ABSTRACT: Craniopharyngiomas are epithelial tumors that typically arise in the suprasellar region of the brain. Patients experience substantial clinical sequelae from both extension of the tumors and therapeutic interventions that damage the optic chiasm, the pituitary stalk and the hypothalamic area. Using whole-exome sequencing, we identified mutations in CTNNB1 (β-catenin) in nearly all adamantinomatous craniopharyngiomas examined (11/12, 92%) and recurrent mutations in BRAF (resulting in p.Val600Glu) in all papillary craniopharyngiomas (3/3, 100%). Targeted genotyping revealed BRAF p.Val600Glu in 95% of papillary craniopharyngiomas (36 of 39 tumors) and mutation of CTNNB1 in 96% of adamantinomatous craniopharyngiomas (51 of 53 tumors). The CTNNB1 and BRAF mutations were clonal in each tumor subtype, and we detected no other recurrent mutations or genomic aberrations in either subtype. Adamantinomatous and papillary craniopharyngiomas harbor mutations that are mutually exclusive and clonal. These findings have important implications for the diagnosis and treatment of these neoplasms.
    Nature Genetics 01/2014; DOI:10.1038/ng.2868 · 29.65 Impact Factor
  • Julie Y Tse, Mai P Hoang
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    ABSTRACT: Adnexal tumors are often benign, rarely malignant, and in some settings they can be associated with a hereditary syndrome that predisposes to visceral malignancies. This article aims to review and update the various genetic syndromes that are characterized by cutaneous appendage neoplasms. Some are of clinical importance due to the association with internal malignancy, and they include Cowden, Gardner, Birt–Hogg–Dubé, Muir–Torre, basal cell nevus and Brooke–Spiegler syndromes. Others are not associated with internal malignancy, such as multiple familial trichoepithelioma, generalized basaloid follicular hamartoma, Bazex–Dupré–Christol, Rombo, Oley and steatocystoma multiplex syndromes. Awareness that some adnexal neoplasms are clues to internal malignancies might allow for early diagnosis, genetic counseling and appropriate cancer surveillance.
    Expert Review of Dermatology 01/2014; 7(3). DOI:10.1586/edm.12.16
  • Journal of the European Academy of Dermatology and Venereology 01/2014; 28(10). DOI:10.1111/jdv.12352 · 3.11 Impact Factor
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    ABSTRACT: Often the distinction of cutaneous apocrine carcinoma from metastatic mammary apocrine carcinoma to the skin can be a diagnostic dilemma because both tumors share similar histologic features and have overlapping immunohistochemical profile. We compared the expression of adipophilin, cytokeratin 5/6, p63, GATA3, mammaglobin, androgen receptor, estrogen receptor, progesterone receptor, and HER2 by immunohistochemistry in 14 cutaneous apocrine carcinomas (11 primary tumors, 3 metastases) and 26 primary apocrine carcinomas of the breast. Whereas focal adipophilin staining was seen in 36% (5/14) of cutaneous apocrine carcinoma, strong and diffuse adipophilin staining was seen in 88% (22/25) of mammary apocrine carcinoma (P = .0013). Differences in estrogen receptor and progesterone receptor expression were also statistically significant (P = .018 and .043). Androgen receptor was strongly positive in all cutaneous and mammary cases. Although there was no significant difference in the frequency of expression of cytokeratin 5/6, p63, HER2, GATA3, and mammaglobin in cutaneous apocrine carcinoma versus mammary apocrine carcinoma, strong and diffuse cytokeratin 5/6 and/or mammaglobin expression were seen only in cutaneous apocrine carcinoma. In conclusion, cutaneous apocrine carcinoma is likely adipophilin- ER+ PR+/- HER2- and can exhibit strong and diffuse cytokeratin 5/6 and/or mammaglobin expression. On the contrary, a mammary apocrine carcinoma is likely adipophilin+ ER- PR- and often exhibit 3+ HER2 with corresponding HER2 gene amplification. A panel of adipophilin, ER, PR, HER2, cytokeratin 5/6, and mammaglobin may be helpful in distinguishing cutaneous apocrine carcinoma from mammary apocrine carcinoma.
    Human pathology 12/2013; 45(2). DOI:10.1016/j.humpath.2013.09.007 · 2.81 Impact Factor
  • 10/2013; 2(1):S58. DOI:10.1016/j.jasc.2013.08.158

Publication Stats

2k Citations
680.96 Total Impact Points


  • 2013–2015
    • Harvard Medical School
      • Department of Pathology
      Boston, Massachusetts, United States
  • 2009–2015
    • Massachusetts General Hospital
      • Department of Pathology
      Boston, Massachusetts, United States
    • University of Massachusetts Medical School
      • Department of Pathology
      Worcester, MA, United States
  • 2009–2014
    • Harvard University
      Cambridge, Massachusetts, United States
  • 1998–2012
    • University of Texas Southwestern Medical Center
      • • Department of Dermatology
      • • Department of Pathology
      Dallas, Texas, United States
  • 1998–2007
    • University of Texas at Dallas
      Richardson, Texas, United States
  • 2000
    • University of Texas Health Science Center at Houston
      Houston, Texas, United States