Mai P Hoang

Harvard Medical School, Boston, Massachusetts, United States

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Publications (145)841.58 Total impact

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    ABSTRACT: Penile clear cell carcinoma originating in skin adnexal glands has been previously reported. Here, we present 3 morphologically distinctive penile tumors with prominent clear cell features originating not in the penile skin but in the mucosal tissues of the glans surface squamous epithelium. Clinical and pathologic features were evaluated. Immunohistochemical stains were GATA3 and p16. Human papilloma virus (HPV) detection by in situ hybridization was performed in 3 cases, and whole-tissue section-polymerase chain reaction was performed in 1 case. Patients' ages were 52, 88, and 95 years. Tumors were large and involved the glans and coronal sulcus in all cases. Microscopically, nonkeratinizing clear cells predominated. Growth was in solid nests with comedo-like or geographic necrosis. Focal areas of invasive warty or basaloid carcinomas showing in addition warty or basaloid penile intraepithelial neoplasia were present in 2 cases. There was invasion of corpora cavernosa, lymphatic vessels, veins, and perineural spaces in all cases. p16 was positive, and GATA3 stain was negative in the 3 cases. HPV was detected in 3 cases by in situ hybridization and in 1 case by polymerase chain reaction. Differential diagnoses included other HPV-related penile carcinomas, skin adnexal tumors, and metastatic renal cell carcinoma. Features that support primary penile carcinoma were tumor location, concomitant warty and/or basaloid penile intraepithelial neoplasia, and HPV positivity. Clinical groin metastases were present in all cases, pathologically confirmed in 1. Two patients died from tumor dissemination at 9 and 12 months after penectomy. Clear cell carcinoma, another morphologic variant related to HPV, originates in the penile mucosal surface and is probably related to warty carcinomas.
    No preview · Article · Feb 2016 · The American journal of surgical pathology
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    Dora Dias-Santagata · Yuhua Su · Mai P. Hoang
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    ABSTRACT: Objectives: Testing for NRAS mutation at codon Q61 is of therapeutic, prognostic, and diagnostic importance for metastatic melanoma, thyroid carcinoma, and colorectal carcinoma. Immunohistochemistry for NRASQ61R, the most common NRAS mutation, offers several practical advantages over current molecular diagnostic techniques.Methods: We investigated the sensitivity and specificity of NRASQ61R in a series of 149 tumors with known NRAS genotype (72 malignant melanomas, 13 melanocytic nevi, 28 thyroid carcinomas, 25 gastrointestinal carcinomas, and 11 other malignancies).Results: Thirty-five cases harbored the NRASQ61R mutation (19 malignant melanomas, one melanocytic nevus, 10 thyroid carcinomas, two gastrointestinal carcinomas, and three other malignancies). In this series, the concordance rate between immunohistochemistry and mutational analyses was 100%. The sensitivity and specificity were 100% and 100%, respectively. However, lower staining intensity was observed for thyroid carcinomas in comparison to melanomas and other tumors.Conclusions: Our studies confirmed that immunohistochemistry provides excellent sensitivity and specificity for detecting the NRASQ61R mutation in a variety of tumor types in a clinical setting.
    Preview · Article · Jan 2016 · American Journal of Clinical Pathology
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    ABSTRACT: Brain metastases are associated with a dismal prognosis. Whether brain metastases harbor distinct genetic alterations beyond those observed in primary tumors is unknown. We performed whole-exome sequencing of 86 matched brain metastases, primary tumors, and normal tissue. In all clonally related cancer samples, we observed branched evolution, where all metastatic and primary sites shared a common ancestor yet continued to evolve independently. In 53% of cases, we found potentially clinically informative alterations in the brain metastases not detected in the matched primary-tumor sample. In contrast, spatially and temporally separated brain metastasis sites were genetically homogenous. Distal extracranial and regional lymph node metastases were highly divergent from brain metastases. We detected alterations associated with sensitivity to PI3K/AKT/mTOR, CDK, and HER2/EGFR inhibitors in the brain metastases. Genomic analysis of brain metastases provides an opportunity to identify potentially clinically informative alterations not detected in clinically sampled primary tumors, regional lymph nodes, or extracranial metastases. SIGNIFICANCE: Decisions for individualized therapies in patients with brain metastasis are often made from primary-tumor biopsies. We demonstrate that clinically actionable alterations present in brain metastases are frequently not detected in primary biopsies, suggesting that sequencing of primary biopsies alone may miss a substantial number of opportunities for targeted therapy.
    Full-text · Article · Sep 2015 · Cancer Discovery
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    ABSTRACT: Congenital dermal melanocytosis (CDM) is a birthmark composed of macular blue-grey hyperpigmentation commonly observed in the lumbosacral region of infants. Generally resolving by childhood, it is traditionally considered a benign condition, but it may be a sign of underlying lysosomal storage disease. We report a case of biopsy-confirmed CDM in a 2-month-old girl of Brazilian descent later diagnosed with infantile GM1 gangliosidosis. © 2015 Wiley Periodicals, Inc.
    No preview · Article · Sep 2015 · Pediatric Dermatology
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    ABSTRACT: Label-free DNA imaging is highly desirable in biology and medicine to perform live imaging without affecting cell function and to obtain instant histological tissue examination during surgical procedures. Here we show a label-free DNA imaging method with stimulated Raman scattering (SRS) microscopy for visualization of the cell nuclei in live animals and intact fresh human tissues with subcellular resolution. Relying on the distinct Raman spectral features of the carbon-hydrogen bonds in DNA, the distribution of DNA is retrieved from the strong background of proteins and lipids by linear decomposition of SRS images at three optimally selected Raman shifts. Based on changes on DNA condensation in the nucleus, we were able to capture chromosome dynamics during cell division both in vitro and in vivo. We tracked mouse skin cell proliferation, induced by drug treatment, through in vivo counting of the mitotic rate. Furthermore, we demonstrated a label-free histology method for human skin cancer diagnosis that provides comparable results to other conventional tissue staining methods such as H&E. Our approach exhibits higher sensitivity than SRS imaging of DNA in the fingerprint spectral region. Compared with spontaneous Raman imaging of DNA, our approach is three orders of magnitude faster, allowing both chromatin dynamic studies and label-free optical histology in real time.
    Full-text · Article · Sep 2015 · Proceedings of the National Academy of Sciences
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    Full-text · Article · Aug 2015 · Cancer Research
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    ABSTRACT: There are limited descriptions of histopathology and immune profiles of new or changing melanocytic nevi in the setting of B-Raf proto-oncogene (BRAF) inhibitor therapy. We sought to identify their distinctive features. Clinical charts and histologic review, neuroblastoma RAS viral (v-ras) oncogene homolog genotyping, and immunohistochemistry for HMB-45, BRAFV600E, phosphorylated extracellular signal-regulated kinase (pERK), phosphorylated protein kinase B, CD4, and CD8 were performed on 19 melanocytic nevi from 10 patients and 23 control nevi. BRAF inhibitors were administered for metastatic melanoma (7), colonic adenocarcinoma (2), and papillary thyroid carcinoma (1). The average duration of BRAF inhibition before lesion excision was 8 months. Frequently associated histologic features included pigmentation of the stratum corneum, hyperpigmented keratinocytes, dermal melanophages, and deep HMB-45 expression. The lesions were BRAFV600E and neuroblastoma RAS viral (v-ras) oncogene homolog wild-type, expressed diffuse weak-moderate pERK, and possessed a predominance of CD8(+) in comparison with CD4(+) T lymphocytes within the dermal infiltrates. This is a retrospective study of a small and heterogeneous group. The nevi associated with BRAF inhibitor therapy invariably lack BRAFV600E mutation. BRAF inhibition appears to cause an increased cytotoxic T-cell response and increased mitogen-activated protein kinase activity in BRAF wild-type lesions, supported by pERK expression, possibly resulting in an activated phenotype characterized by increased melanin pigmentation and deep HMB-45 expression. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Jul 2015 · Journal of the American Academy of Dermatology
  • Mark C Mochel · Adriano Piris · Vania Nose · Mai P Hoang
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    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.
    No preview · Article · Jun 2015 · American Journal of Clinical Pathology
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    ABSTRACT: 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). 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. 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.
    No preview · Article · May 2015
  • M. P. Hoang · J. Reuter · J. A. Papalas · L. Edwards · M. A. Selim

    No preview · Article · Apr 2015 · American Journal of Dermatopathology
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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.
    Full-text · Article · Mar 2015 · Journal of the American Academy of Dermatology
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    Sebastian H Unizony · Nancy D Kim · Mai P Hoang
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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.
    Preview · Article · Feb 2015 · New England Journal of Medicine

  • No preview · Article · Feb 2015 · Circulation
  • Jonathan J. Lee · Daniela Kroshinsky · Mai P. Hoang
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    ABSTRACT: Acute generalized exanthematous pustulosis (AGEP) is an acute, self-limited, widespread cutaneous eruption characterized by the development of numerous, non-follicular, sterile pustules on a background of erythematous, edematous skin. The eruption usually develops within hours to days of exposure to medications (antibiotics, antifungals, calcium channel blockers, and carbamazepine most commonly), but it has also been documented to be associated with various infections (mostly viral), spider bites, and herbal medications. After the inciting medication is removed or precipitant infection clears, the skin reaction resolves spontaneously within 1–2 weeks. The histologic hallmark of AGEP is spongiform subcorneal and/or intraepidermal pustules with marked papillary edema, polymorphous perivascular infiltrates with neutrophils, and exocytosis of some eosinophils. AGEP is immunologically mediated by a T cell-orchestrated neutrophil response through the expression of neutrophilotactic chemokines such as CXCL8.
    No preview · Chapter · Jan 2015
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    ABSTRACT: Pompe disease, an inherited deficiency of lysosomal acid alpha-glucosidase (GAA), is a metabolic myopathy with heterogeneous clinical presentations. Late-onset Pompe disease (LOPD) is a debilitating progressive muscle disorder that can occur anytime from early childhood to late adulthood. Enzyme replacement therapy (ERT) with recombinant human GAA is currently available for Pompe patients. Although ERT shows some benefits, the reversal of skeletal muscle pathology - lysosomal glycogen accumulation and autophagic buildup - remains a challenge. In this study, we examined the clinical status and muscle pathology of 22 LOPD patients and one atypical infantile patient on ERT to understand the reasons for muscle resistance to ERT. The patients were divided into three groups for analysis, based on the age of onset and diagnosis: adult-onset patients, juvenile-onset patients, and those identified through newborn screening (NBS). The areas of autophagic buildup found in patients’ biopsies of all three groups, contained large autofluorescent inclusions which we show are made of lipofuscin, an indigestible intralysosomal material typically associated with ageing. These inclusions, analysed by staining, spectral analysis, time-resolved Fluorescence Lifetime Imaging (FLIM), and Second Harmonic Generation (SHG) imaging, were the major pathology remaining in many fibers after ERT. The best outcome of ERT both clinically and morphologically was observed in the NBS patients. The muscle biopsy, in spite of its shortcomings, allowed us to recognize an underreported, ERT-resistant pathology in LOPD; numerous lysosomes and autolysosomes loaded with lipofuscin appear to be a hallmark of LOPD skeletal muscle. Lipofuscin accumulation - a result of inefficient lysosomal degradation - may in turn exacerbate both lysosomal and autophagic abnormalities.
    Full-text · Article · Dec 2014 · Acta Neuropathologica
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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.
    Full-text · Article · Nov 2014 · Modern Pathology
  • Adriano Piris M.D. · Martin C. Mihm Jr. M.D · Mai P. Hoang M.D.
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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.
    No preview · Article · Nov 2014 · Human pathology
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    ABSTRACT: Background: 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. Objective: We sought to evaluate the utility of re-excising margin-positive mildly and moderately DN. Methods: A retrospective chart review was conducted on all adult patients given the diagnosis of a biopsy-proven DN from 2010 through 2011. The primary outcomes were defined as the presence of melanocytic residuum in re-excisional specimens and a clinically significant change in diagnosis. Results: A total of 1809 mildly and moderately DN were diagnosed from 2010 through 2011. In all, 765 (42.3%) of these lesions were found to have positive surgical margins during biopsy, and 495 (64.7) of the 765 lesions were subsequently re-excised. Melanocytic residuum was present in 18.2% of re-excisional specimens. Re-excision resulted in a clinically significant alteration of the diagnosis in only 1 case (0.2%). Limitations: Limitations include retrospective design and inability to assess for malignant transformation given limited follow-up. Conclusions: Re-excising mildly and moderately DN results in a low histopathological yield and rarely results in a clinically significant change in diagnosis. As such, clinical monitoring of margin-positive lesions may be warranted.
    No preview · Article · Sep 2014 · Journal of the American Academy of Dermatology
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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.
    No preview · Article · Sep 2014 · The American Journal of dermatopathology
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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.
    Preview · Article · Jun 2014 · American Journal of Clinical Pathology

Publication Stats

2k Citations
841.58 Total Impact Points

Institutions

  • 2015
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 2010-2015
    • Massachusetts General Hospital
      • Department of Pathology
      Boston, Massachusetts, United States
  • 2009-2015
    • Harvard University
      Cambridge, Massachusetts, United States
  • 1998-2008
    • University of Texas Southwestern Medical Center
      • Department of Pathology
      Dallas, Texas, United States
  • 2007
    • University of Pittsburgh
      Pittsburgh, Pennsylvania, United States
  • 2001-2007
    • University of Texas at Dallas
      Richardson, Texas, United States
    • Johns Hopkins Medicine
      Baltimore, Maryland, United States
  • 2005
    • Saint Luke's Hospital (NY, USA)
      New York City, New York, United States
  • 2000
    • University of Texas Health Science Center at Houston
      Houston, Texas, United States