Publications by authors named "May P Chan"

70 Publications

Verruciform and Condyloma-like Squamous Proliferations in the Anogenital Region.

Authors:
May P Chan

Arch Pathol Lab Med 2019 07 11;143(7):821-831. Epub 2018 Sep 11.

From the Department of Pathology, University of Michigan Health System, Ann Arbor.

Context.—: Histologic distinction between condyloma acuminatum and various benign and malignant condyloma-like lesions in the anogenital area poses a common diagnostic challenge to pathologists across subspecialties.

Objective.—: To review the overlapping and distinguishing features of condyloma acuminatum and its mimics, and to clarify confusing terminology and diagnostic criteria for problematic entities.

Data Sources.—: A review of the literature on condyloma acuminatum (ordinary and giant types), verrucous carcinoma, warty/warty-basaloid high-grade squamous intraepithelial lesion and squamous cell carcinoma, papillary squamous cell carcinoma, bowenoid papulosis, verruca vulgaris, epidermolytic acanthoma, and verruciform xanthoma was performed.

Conclusions.—: Correct diagnosis of condyloma acuminatum and condyloma-like lesions has important clinical implication and entails familiarization with their clinical presentations and histopathologic features. Contrary to historical belief, giant condyloma acuminatum and verrucous carcinoma should be considered distinct entities based on different pathogenetic pathways. Ancillary tools available for identifying and genotyping human papillomavirus can aid in diagnosis when histopathologic findings are inconclusive. Recognition of relatively rare entities such as bowenoid papulosis, epidermolytic acanthoma, and verruciform xanthoma would avoid overdiagnosis and unnecessary, overaggressive treatment.
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http://dx.doi.org/10.5858/arpa.2018-0039-RADOI Listing
July 2019

Chronic ulcerative stomatitis: Case series of an under-recognized entity.

J Cutan Pathol 2018 Dec 25;45(12):927-932. Epub 2018 Sep 25.

Department of Pathology, University of Michigan, Ann Arbor, Michigan.

Chronic ulcerative stomatitis (CUS) is a mucocutaneous condition characterized by chronic relapsing and remitting oral ulcers and erosions. This condition remains under-recognized among dermatopathologists, possibly because of common misdiagnosis as oral erosive lichen planus (LP). We report five cases of CUS in order to raise awareness of this uncommon condition. All patients presented with desquamative gingivitis and/or oral erosions, with biopsies showing lichenoid mucositis and epithelial nuclear IgG deposition on direct immunofluorescence. Recognition of the characteristic direct immunofluorescence findings allows for distinction of chronic ulcerative stomatitis from oral LP and appropriate therapy.
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http://dx.doi.org/10.1111/cup.13347DOI Listing
December 2018

Incidental diagnosis of blastic plasmacytoid dendritic cell neoplasm in skin excision for basal cell carcinoma.

J Cutan Pathol 2018 Nov 4;45(11):873-875. Epub 2018 Sep 4.

Department of Pathology, University of Michigan, Ann Arbor, Michigan.

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http://dx.doi.org/10.1111/cup.13338DOI Listing
November 2018

Metastatic melanoma with diffuse melanosis histologically after stable response to talimogene laherparepvec therapy.

JAAD Case Rep 2018 May 4;4(4):379-381. Epub 2018 Apr 4.

Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan.

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http://dx.doi.org/10.1016/j.jdcr.2018.01.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5911974PMC
May 2018

Subungual atypical lentiginous melanocytic proliferations in children and adolescents: A clinicopathologic study.

J Am Acad Dermatol 2018 Aug 27;79(2):327-336.e2. Epub 2018 Mar 27.

Department of Pathology, University of Michigan, Ann Arbor, Michigan; Department of Dermatology, University of Michigan, Ann Arbor, Michigan. Electronic address:

Background: Most subungual melanocytic lesions in children are benign, but some are difficult to classify due to prominent lentiginous growth and high-grade cytologic atypia.

Objective: To characterize the clinicopathologic features of these rare lesions.

Methods: Subungual atypical lentiginous melanocytic proliferations from patients <20 years of age were collected for clinical and histopathologic review. Fluorescence in situ hybridization (FISH) was performed when possible.

Results: Eleven patients aged 2-19 years had expanding or darkening longitudinal pigmented streak(s) with or without Hutchinson sign. Microscopically, all revealed predominantly single-cell growth, pagetoid scatter, and poor circumscription. Eight (73%) cases showed focal or poor nesting, and 3 (27%) demonstrated confluence. Nuclear enlargement, hyperchromasia, and angulation were present in 8 (73%) cases, 7 (64%) cases, and 6 (55%) cases, respectively. One of 4 cases tested by FISH was positive. Three lesions recurred locally without other adverse outcome.

Limitations: Small sample size and short clinical follow-up. Two cases were examined in partial biopsies only.

Conclusion: Some subungual melanocytic lesions in children and adolescents are histologically indistinguishable from adult subungual melanoma in situ. While the biologic potential remains elusive, FISH might aid in risk stratification. Awareness of this rare group of lesions is crucial for facilitating future investigation into its biologic behavior.
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http://dx.doi.org/10.1016/j.jaad.2018.03.030DOI Listing
August 2018

Unsuspected lymphomatoid granulomatosis in a patient with antisynthetase syndrome.

Cutis 2017 Oct;100(4):E22-E26

Department of Dermatology, Department of Pathology, University of Michigan, Ann Arbor, USA.

Clinical diagnosis of lymphomatoid granulomatosis (LYG) often is difficult, especially in patients with multiple comorbidities. We present a 60-year-old woman with worsening fatigue, night sweats, unintentional weight loss, and dyspnea of 2 weeks' duration. Her medical history was remarkable for recent radiation therapy for recurrent breast cancer and antisynthetase syndrome complicated by interstitial lung disease and controlled with azathioprine. Computed tomography showed ground-glass opacities and nodular infiltrates in all lung lobes, raising concern for radiation pneumonitis and drug toxicity. Skin examination revealed erythematous and hemorrhagic papules, macules, and blisters on the lower leg. A diagnosis of LYG was made on a skin biopsy showing large angiocentric Epstein-Barr virus (EBV)-positive B cells. The patient soon progressed to develop nodal large B-cell lymphoma and died 6 weeks later. This rare report of LYG in a patient with antisynthetase syndrome highlights the diagnostic difficulty and aggressive course of LYG as well as the important role of skin biopsy in establishing the diagnosis.
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October 2017

Syphilis of the Aerodigestive Tract.

Am J Surg Pathol 2018 04;42(4):472-478

Department of Pathology, Massachusetts General Hospital, Boston, MA.

Syphilis, a sexually transmitted infection caused by the Gram-negative bacterium Treponema pallidum, is increasing in prevalence in the United States. It has been our experience that primary and secondary syphilis of the aerodigestive tract can afflict a large age spectrum with varied clinical and histopathologic findings, which can lead to diagnostic problems and frequent misdiagnosis. In this study, we describe the histopathologic patterns of syphilis of the aerodigestive tract to expand awareness of its varied appearance. We identify 3 patterns of inflammatory response to syphilis: plasma cell-rich, lymphohistiocytic, and lymphoma-like. We also report the presence of immunoglobulin G4-predominant plasma cells in the inflammatory response as a potential mimicker of immunoglobulin G4-related disease. Lastly, we found that use of T. pallidum immunohistochemical stain is more reliable than Steiner silver stain at the identification of spirochetes. Our study highlights that despite convention, plasma cells are not always abundant in syphilis. Awareness of the histopathologic range of syphilis in the aerodigestive tract by the surgical pathologist can lead to the correct diagnosis and guide appropriate treatment.
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http://dx.doi.org/10.1097/PAS.0000000000000987DOI Listing
April 2018

Psammomatous Squamous Cell Carcinoma of the Skin.

Am J Dermatopathol 2018 Mar;40(3):e38-e40

Departments of Pathology, and.

Psammoma bodies (PBs) are concentric, lamellated calcifications commonly observed in malignancies such as papillary thyroid carcinoma and serous carcinoma of the ovary in which they may serve prognostic value. PBs are rare in cutaneous squamous cell carcinoma (cSCC), with only 1 previously reported case. Here, we present 3 cases of cSCC displaying PBs. One case occurred in the setting of end-stage renal disease, whereas the other 2 cases were in patients who did not have comorbid conditions that might predispose to hypercalcemia and dystrophic calcification. All 3 tumors demonstrated classic immunophenotypic findings of cSCC. Our findings indicate that PBs are a rare but recurrent phenomenon in cSCC, with unknown prognostic significance. The potential for PB formation in cSCC should be kept in mind, as this may represent a diagnostic pitfall in tumors with limited sampling or unusual morphologies.
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http://dx.doi.org/10.1097/DAD.0000000000001001DOI Listing
March 2018

Comprehensive histopathological comparison of epidermotropic/dermal metastatic melanoma and primary nodular melanoma.

Histopathology 2018 Feb 21;72(3):472-480. Epub 2017 Nov 21.

Department of Pathology, University of Michigan, Ann Arbor, MI, USA.

Aims: Metastatic melanoma involving the epidermis and/or upper dermis may show significant histological overlap with primary cutaneous melanoma, especially the nodular subtype. Proper histopathological classification is crucial to appropriate staging and management, but is often challenging. The aim of this study was to identify helpful histopathological features for differentiating epidermotropic/dermal metastatic melanoma (EDMM) and primary nodular melanoma (PNM).

Methods And Results: A cohort of EDMMs (n = 74) and PNMs (n = 75) was retrospectively reviewed for various histopathological features, and the data were compared between groups by the use of univariate analysis. Features significantly associated with EDMM included a tumour size of <2 mm, an absence of tumour-infiltrating lymphocytes and plasma cells, monomorphism, and involvement of adnexal epithelium. Features associated with PNM included a polypoid (exophytic) configuration, prominent tumour-infiltrating plasma cells (TIPs), a tumour size of >10 mm, ulceration, epidermal collarettes, a higher mitotic rate, necrosis, multiple phenotypes, significant pleomorphism, and lichenoid inflammation. In multivariate analysis, a logistic regression model including large tumour size, ulceration, prominent TIPs, lichenoid inflammation and epidermal collarettes was highly predictive of PNM. Six (8%) EDMMs from three patients showed an 'epidermal-only' or 'epidermal-predominant' pattern closely simulating in-situ or microinvasive melanoma. Two of these cases were tested by fluorescence in-situ hybridisation, which confirmed clonal relationships with their corresponding primary melanomas.

Conclusions: This is the first comprehensive histopathological comparison of EDMM and PNM. Recognition of the above histopathological associations should aid in the correct classification and staging of cutaneous melanoma. Epidermotropic metastatic melanomas may occasionally show an epidermal-only/epidermal-predominant pattern; accurate diagnosis requires prudent clinical correlation and, when necessary, ancillary molecular tests.
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http://dx.doi.org/10.1111/his.13384DOI Listing
February 2018

Gynecologic melanomas: A clinicopathologic and molecular analysis.

Gynecol Oncol 2017 11 24;147(2):351-357. Epub 2017 Aug 24.

Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, United States; Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, United States. Electronic address:

Objective: Melanoma originating from gynecologic sites (MOGS), including the vulva, vagina, and cervix, is a rare and aggressive form of melanoma with poor long-term clinical outcome. The clinicopathologic features of vulvar and non-vulvar tumors remain relatively understudied, and in contrast to cutaneous melanomas at non-sun-exposed sites, MOGS typically do not harbor BRAF mutations. Thus, we sought to analyze the clinicopathologic and molecular features of MOGS.

Methods: A large retrospective cohort of patients with MOGS (n=59) at a single large academic institution over a 28-year period was identified. Associations among clinicopathologic characteristics were assessed via standard statistical approaches, and clinical outcome was examined using Cox regression analysis. Sanger sequencing was utilized to identify mutations in hotspot regions of BRAF, KIT, NRAS, and CTNNB1.

Results: Tumors involving the vagina and/or cervix (non-vulvar) are significantly associated with high-risk clinicopathologic features, including increased tumor thickness, ulceration, positive resection margins, lymph node metastasis, and poor long-term clinical outcome (with increased risk of death due to disease). The aggressive clinical behavior of non-vulvar tumors is independent of advanced clinical stage and lymph node metastasis in multivariate analysis. Targeted molecular analysis confirms an overall low rate of oncogenic mutations in our MOGS cohort, although KIT mutations (particularly in exon 11) are relatively enriched.

Conclusions: Overall, our results show that non-vulvar MOGS are aggressive tumors with poor long-term clinical outcome and indicate that few targeted therapeutic options are currently available to patients with MOGS.
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http://dx.doi.org/10.1016/j.ygyno.2017.08.023DOI Listing
November 2017

Inflammatory Dermatopathology for General Surgical Pathologists.

Clin Lab Med 2017 09;37(3):673-696

Department of Pathology, University of Michigan, 1301 Catherine Street, Medical Science I, M3261, Ann Arbor, MI 48109, USA; Department of Dermatology, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA. Electronic address:

Owing to the wide variety and complexity of inflammatory skin diseases, inflammatory dermatopathology can be a challenging topic for dermatopathologists and general surgical pathologists alike. Following a basic tissue reaction pattern approach, this article reviews the most common and important entities of each pattern, with emphasis on differential diagnosis, diagnostic pitfalls, and appropriate workup when indicated. A few dermatologic emergencies are also discussed.
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http://dx.doi.org/10.1016/j.cll.2017.05.008DOI Listing
September 2017

Comparative Analysis of Chilblain Lupus Erythematosus and Idiopathic Perniosis: Histopathologic Features and Immunohistochemistry for CD123 and CD30.

Am J Dermatopathol 2018 Apr;40(4):265-271

Departments of Pathology, and.

Distinction of chilblain lupus erythematosus (CLE) from idiopathic perniosis (IP) could predict an underlying connective tissue disease; however, histopathologic discrimination of the two is difficult. Increased CD123 plasmacytoid dendritic cells and CD30 lymphocytes have been demonstrated in various forms of cutaneous lupus erythematosus and IP, respectively. To our knowledge, CD123 and CD30 have not been examined in CLE. Our objective was to identify helpful histopathologic and immunohistochemical features in distinguishing CLE and IP. Skin biopsies classified as CLE (n = 20) and IP (n = 39) based on clinicopathologic correlation were collected from 2000 to 2015. Various histopathologic features were examined on hematoxylin and eosin and alcian blue stains. CD123 and CD30 immunostains were performed and characterized. We identified dermal interstitial fibrin exudate (P = 0.0352) and increased dermal mucin (P = 0.0002) as features significantly associated with CLE. Other histopathologic features and CD123 failed to distinguish between groups. CD30 lymphocytes were sparse in all cases. Despite being the largest series of CLE and IP to date, the number of CLE cases in this study remained relatively limited, and some patients in the IP group may have yet to develop diagnostic features of systemic lupus erythematosus. In conclusion, histopathologic distinction between CLE and IP remains challenging. Interstitial fibrin and abundant dermal mucin help favor CLE. The number and distribution of CD123 plasmacytoid dendritic cells and CD30 lymphocytes have no discriminatory role.
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http://dx.doi.org/10.1097/DAD.0000000000000945DOI Listing
April 2018

Superficial papular neuroma: Case series of a new entity.

J Cutan Pathol 2017 Sep 13;44(9):757-762. Epub 2017 Jul 13.

Department of Pathology, University of Michigan, Ann Arbor, Michigan.

Background: Dermal neural lesions arise in various circumstances and may be difficult to classify.

Methods: We describe the clinical, histopathologic and immunophenotypic features of a series of terminally differentiated neural lesions not described previously, to our knowledge.

Results: Four cases from men aged 58 to 66 years were included. Some lesions reportedly bled, but no inciting trauma or prior biopsies were reported. None recurred after biopsy, with follow-up ranging from 19 to 113 months. All lesions were papular, with vertically oriented S100-positive spindled cells and nerve fibers in the papillary dermis. Slight epidermal hyperplasia, dilated superficial thin-walled vessels and minimal to mild inflammation were seen in each. Fibers were uniformly fine in 3 cases, with slightly thicker central fibers in the fourth. Three had parakeratotic scale. None were associated with dermal fibrosis or adnexal proliferation. Neurofilament stained axons in each. EMA was negative in all cases. CD34, melan-A and HMB45 were negative when performed.

Conclusions: We report a small series of benign neural lesions and propose the name "superficial papular neuroma" for this distinct entity. Awareness is important to understand the clinical significance of these lesions and avoid misinterpretation that could lead to overtreatment, unnecessary work-up and increased cost.
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http://dx.doi.org/10.1111/cup.12981DOI Listing
September 2017

Detection of Occult Invasion in Melanoma in Situ-Reply.

JAMA Dermatol 2017 06;153(6):611-612

Department of Dermatology, University of Michigan, Ann Arbor3Division of Plastic Surgery, Department of Surgery, University of Michigan, Ann Arbor4Department of Otolaryngology, University of Michigan, Ann Arbor.

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http://dx.doi.org/10.1001/jamadermatol.2017.0197DOI Listing
June 2017

Immunohistochemical Characterization of Fumarate Hydratase (FH) and Succinate Dehydrogenase (SDH) in Cutaneous Leiomyomas for Detection of Familial Cancer Syndromes.

Am J Surg Pathol 2017 Jun;41(6):801-809

Departments of *Pathology §Dermatology †Comprehensive Cancer Center, University of Michigan Health System ‡Michigan Center for Translational Pathology, Ann Arbor, MI.

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is caused by germline mutations in the FH gene, and is associated with increased incidence of leiomyomas and a potentially aggressive variant of renal cell carcinoma (HLRCC-associated RCC). Absent immunohistochemical expression of fumarate hydratase (FH) has previously been used to diagnose HLRCC-associated RCC, but immunohistochemical staining of leiomyomas is not standard practice. We performed immunohistochemistry (IHC) on whole sections from consecutive cutaneous leiomyomas from our archives to evaluate for both FH and succinate dehydrogenase B expression, in addition to clinicopathologic data collection and review of all hematoxylin and eosin-stained slides for blinded morphologic evaluation of features reported to be seen in HLRCC-associated uterine leiomyomas. Ninety-six cutaneous leiomyomas from 87 patients were identified; 12 of these specimens were from 7 patients with documented HLRCC. FH expression by IHC was absent in 9 specimens and retained in 85 specimens; 2 cases were equivocal with minimal FH expression. Seven of the 9 absent expression specimens were from patients with HLRCC, as were both of the equivocal specimens. The overall sensitivity and specificity of absent FH expression in leiomyomas for detection of patients with HLRCC were 70.0% and 97.6%, respectively. Inclusion of cases classified as equivocal increased sensitivity to 75.0%. Succinate dehydrogenase B expression was retained in 95 specimens and equivocal in 1 specimen. None of the evaluated morphologic features showed any association with leiomyomas in HLRCC. Loss of FH immunohistochemical expression in cutaneous leiomyomas is a sensitive and specific marker for detection of HLRCC, thus suggesting a role for prospective FH IHC in patients with these tumors to screen for HLRCC.
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http://dx.doi.org/10.1097/PAS.0000000000000840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5423817PMC
June 2017

Protein gene product 9.5 (PGP9.5) expression in benign cutaneous mesenchymal, histiocytic, and melanocytic lesions: comparison with cellular neurothekeoma.

Pathology 2017 Jan 30;49(1):44-49. Epub 2016 Nov 30.

Department of Pathology, University of Michigan, Ann Arbor, MI, United States; Department of Dermatology, University of Michigan, Ann Arbor, MI, United States. Electronic address:

Cellular neurothekeoma (CNTK) frequently enters the differential diagnosis of a benign dermal cellular proliferation. Diagnosis often relies on immunohistochemistry including the use of protein gene product 9.5 (PGP9.5). A previous study demonstrated PGP9.5 expression across a wide variety of soft tissue neoplasms. We explored the utility of this antibody in distinguishing CNTK from other benign dermal-based lesions. A cohort of CNTK (n=7) and benign cutaneous lesions of neural (n=28), fibrohistiocytic (n=23), fibroblastic (n=25), histiocytic (n=18), myofibroblastic (n=7), smooth muscle (n=14), and melanocytic (n=12) differentiations were immunostained with PGP9.5. Staining was graded by H-score and compared with CNTK. A significantly higher H-score was found in CNTK compared with the fibrohistiocytic (p=0.0001), histiocytic (p=0.0016), myofibroblastic (p=0.0003), smooth muscle (p<0.0001), and melanocytic (p=0.0004) groups, with the exceptions of plexiform fibrohistiocytic tumour, xanthoma, and xanthogranuloma. No significant difference was found when comparing CNTK with fibroblastic and neural lesions, with the exceptions of neurofibroma and perineurioma. In conclusion, PGP9.5 is helpful in distinguishing CNTK from most benign cutaneous fibrohistiocytic, histiocytic, myofibroblastic, smooth muscle, and melanocytic lesions. In addition to CNTK and neural lesions, PGP9.5 is also expressed in benign fibroblastic lesions, and therefore distinction of these lesions should not be based on PGP9.5 positivity.
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http://dx.doi.org/10.1016/j.pathol.2016.09.061DOI Listing
January 2017

Loss of p16 expression and copy number changes of CDKN2A in a spectrum of spitzoid melanocytic lesions.

Hum Pathol 2016 12 26;58:152-160. Epub 2016 Aug 26.

Department of Pathology, University of Michigan Health System, Ann Arbor, MI 48109; Department of Dermatology, University of Michigan Health System, Ann Arbor, MI 48109.

Spitzoid melanocytic lesions, including Spitz nevi (benign), spitzoid melanoma (malignant), and borderline atypical Spitz tumors (ASTs), frequently present challenges for accurate diagnosis and prognosis. Evaluation for loss of the tumor suppressor p16, encoded by CDKN2A gene on chromosome 9p21.3, has been proposed to be useful for evaluation of spitzoid melanocytic lesions. However, reports on the utility of p16 immunohistochemistry for spitzoid lesions have been conflicting, and few studies have directly compared p16 immunohistochemistry with fluorescence in situ hybridization (FISH) for CDKN2A genomic status. We analyzed a spectrum of benign (n=24), borderline (n=27), and malignant (n=19) spitzoid lesions for p16 protein expression by immunohistochemistry and CDKN2A copy number by FISH. Immunohistochemistry was evaluated by 2 scoring methods: H score and 2-tiered score (positive or negative for p16 loss). By immunohistochemistry, loss of p16 expression was not observed in Spitz nevi (0/24) but was seen in ASTs (7/27; 26%) and spitzoid melanomas (3/19; 16%). By H score, p16 expression was significantly higher in Spitz nevi relative to ASTs or spitzoid melanomas. Similarly, copy number aberrations of CDKN2A by FISH were absent in Spitz nevi but were found in 2 (9.5%) of 21 ASTs and 4 (33%) of 12 spitzoid melanomas. Our findings from this large cohort suggest that p16 aberrations are highly specific for borderline and malignant spitzoid neoplasms relative to Spitz nevi. Similar to ASTs, p16 loss in spitzoid melanomas may occur in the presence or absence of genomic CDKN2A loss.
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http://dx.doi.org/10.1016/j.humpath.2016.07.029DOI Listing
December 2016

Detection of Occult Invasion in Melanoma In Situ.

JAMA Dermatol 2016 11;152(11):1201-1208

Department of Dermatology, University of Michigan Medical School and Comprehensive Cancer Center, Ann Arbor4Department of Pathology, University of Michigan Medical School and Comprehensive Cancer Center, Ann Arbor.

Importance: It is unclear why some patients with in situ melanoma develop metastases. Few reports demonstrate occult invasion with immunohistochemistry staining, which were discordant with reports interpreting such staining as false-positive.

Objective: To investigate the occurrence of occult invasive disease within in situ melanoma by using methods to circumvent potential limitations in prior study designs.

Design, Setting, And Participants: Unequivocal in situ melanoma without associated nevi or regression was identified using a consecutive sample of 33 cases plus 1 index case in an academic medical center. After cutting deeper into the most representative tissue block, 3 sequential slides were stained with hematoxylin-eosin (H-E), melanoma antigen (melan-A), and again with H-E. Melan-A-stained slides showing definitive invasion were double-stained with Sry-related HMg-Box gene 10 (SOX10) to confirm the melanocytic nature of the cells of interest. The study evaluated the possibilities of occult invasion detected by immunohistochemistry, sectioning deeper into the tissue block, or both. Slides were independently scored by 3 dermatopathologists with interrater reliability assessed. The study was conducted from January 1, 2012, to July 31, 2014.

Main Outcomes And Measures: Assessment of the occurrence of occult invasion, diagnosis of invasion by immunohistochemistry alone vs cutting deeper into the tissue block, and occurrence of false-positive results using immunohistochemistry alone.

Results: Occult invasive melanoma was detected in 11 of 33 consecutive cases (33%) of previously diagnosed unequivocal in situ melanoma. Six of 11 melanomas (55%) were diagnosable only by immunohistochemistry. The remaining 5 tumors (45%) were diagnosable by both melan-A and H-E staining, likely as a result of simply cutting deeper into the tissue block. Four cases (12%) showed a few melan-A-positive cells in the dermis, which was insufficient for a diagnosis of invasive melanoma and most consistent on a cytomorphologic basis with occult nevi.

Conclusions And Relevance: Although rare, in situ melanoma may metastasize. Occult microinvasion was demonstrated in up to one-third of the specimens in the present study, which provides a plausible explanation for this adverse event. Thus, history and physical examination including regional lymph nodes, education, and surveillance recommendations should be based on a very low, but not zero, risk of metastasis.
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http://dx.doi.org/10.1001/jamadermatol.2016.2668DOI Listing
November 2016

Assessment of Melanocyte Density in Anorectal Mucosa for the Evaluation of Surgical Margins in Primary Anorectal Melanoma.

Am J Clin Pathol 2016 May;145(5):626-34

From the Department of Pathology, Massachusetts General Hospital, Boston

Objectives: Accurate histopathologic evaluation of surgical resection margins for anorectal melanoma (AM) is diagnostically challenging but essential to clinical management. We studied intraepithelial melanocyte density and growth pattern in anorectal mucosa and BRAF V600E mutation status in AM compared to controls.

Methods: Histomorphology and melanocytic immunostains, microphthalmia transcription factor (MITF) and human melanoma black 45 (HMB45), were evaluated. Utility of VE1 immunostaining for determination of BRAF V600E mutation status was studied.

Results: Immunostains aid in the distinction between "trailing" melanoma in situ (MIS) and benign melanocyte hyperplasia (BMH), by facilitating assessment of melanocyte density, and evaluation of nuclear atypia and growth pattern. While respective melanocyte densities overlapped, "trailing" MIS could be distinguished by melanocyte nuclear atypia and near confluent growth, compared to the banal cytology and scattered growth of BMH.

Conclusions: In the histopathologic assessment of AM resections, MITF and HMB45 immunostains aid in distinguishing between "trailing" MIS and BMH, by highlighting melanocyte density, nuclear atypia, and growth pattern, with the latter two being reliable features. VE1 showed nonspecific immunopositivity in anorectal glandular epithelium, a potential diagnostic pitfall when assessing BRAF mutation status.
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http://dx.doi.org/10.1093/ajcp/aqw047DOI Listing
May 2016

Painful losses.

J Hosp Med 2016 10 25;11(10):730-734. Epub 2016 May 25.

Division of General Medicine, Department of Internal Medicine, VA Ann Arbor Healthcare System, University of Michigan, Ann Arbor, Michigan.

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http://dx.doi.org/10.1002/jhm.2610DOI Listing
October 2016

Immunohistochemical evaluation of p16 expression in cutaneous histiocytic, fibrohistiocytic and undifferentiated lesions.

J Cutan Pathol 2016 Aug 6;43(8):671-8. Epub 2016 Jun 6.

Department of Dermatology, University of Michigan, Ann Arbor, MI, USA.

Background: Expression of p16 is frequently evaluated in melanocytic lesions. Expression of p16 in cutaneous histiocytic, fibrohistiocytic and undifferentiated lesions has not been well characterized.

Methods: We evaluated p16 expression in a cohort of histiocytic (reticulohistiocytoma, Langerhans cell histiocytosis, xanthogranuloma, Rosai Dorfman disease and xanthoma), fibrohistiocytic (dermatofibroma, epithelioid fibrous histiocytoma and dermatofibrosarcoma protuberans) and undifferentiated (atypical fibroxanthoma and pleomorphic undifferentiated sarcoma) lesions. A group of melanocytic lesions (Spitz nevus, ordinary nevus, spitzoid melanoma and non-spitzoid melanoma) were also evaluated as reference. Each case was scored by the proportion of p16-positive cells and by staining intensity.

Results: Immunoreactivity for p16 was found in almost all histiocytic (28/30, 93%) and fibrohistiocytic (22/24, 92%) lesions. About half of the undifferentiated lesions also exhibited p16 staining (9/17, 53%). Most of the melanocytic cases examined in this study expressed p16. A wide range of staining intensity and proportion of p16-positive cells was observed in most groups.

Conclusion: Expression of p16 is common, albeit variable in proportion and intensity, amongst a wide variety of cutaneous histiocytic, fibrohistiocytic and undifferentiated lesions. Further studies are required to determine if p16 expression is useful in distinguishing benign from malignant neoplasms of these types.
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http://dx.doi.org/10.1111/cup.12730DOI Listing
August 2016

EZH2, Proliferation Rate, and Aggressive Tumor Subtypes in Cutaneous Basal Cell Carcinoma.

JAMA Oncol 2016 07;2(7):962-3

Department of Ophthalmology and Visual Sciences, W. K. Kellogg Eye Center, Ann Arbor, Michigan3Comprehensive Cancer Center, University of Michigan, Ann Arbor.

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http://dx.doi.org/10.1001/jamaoncol.2016.0021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4945394PMC
July 2016

Cytokeratin 17 is highly sensitive in discriminating cutaneous lymphadenoma (a distinct trichoblastoma variant) from basal cell carcinoma.

J Cutan Pathol 2016 May 6;43(5):422-9. Epub 2016 Apr 6.

Dermatopathology Unit, Massachusetts General Hospital, Boston, MA, USA.

Background: Cutaneous lymphadenoma (CL) is rare neoplasm that clinically and histologically resembles basal cell carcinoma (BCC). CL, composed of dermal basaloid epithelial islands with prominent admixed lymphocytes, characteristically contains cytokeratin 20 (CK20)-positive Merkel cells (MCs). However, CK20 may be of limited use because of low MC density in small samples. CK17 is expressed diffusely throughout BCC. We investigated the discriminatory utility of CK17 and CK20 in CL and BCC.

Methods: A retrospective clinicopathological review of 11 cases of CL and 14 BCC was performed. CK20-positive MCs within basaloid tumor lobules and CK17 immunohistochemical staining and pattern of expression were recorded.

Results: Intratumoral CK20-positive MCs were identified in 4/11 CL cases (36.4%) and 0/14 BCC cases (p = 0.012, sensitivity = 0.36). CK17 showed diffuse positive staining in all 14 BCC cases. CK17 showed a distinct patchy and peripheral rim staining in basaloid islands of 10/11 CL cases (p < 0.001, sensitivity = 0.91); one case showed patchy staining throughout tumor lobules.

Conclusions: In cases with a differential diagnosis of CL and BCC, CK20 staining of intratumoral MCs has a high positive predictive value for CL but is of low sensitivity. The pattern of CK17 expression is a highly sensitive marker for distinguishing CL from BCC in small samples.
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http://dx.doi.org/10.1111/cup.12700DOI Listing
May 2016

Genomic copy number analysis of a spectrum of blue nevi identifies recurrent aberrations of entire chromosomal arms in melanoma ex blue nevus.

Mod Pathol 2016 Mar 8;29(3):227-39. Epub 2016 Jan 8.

Department of Pathology, University of Michigan, Ann Arbor, MI, USA.

Blue nevi may display significant atypia or undergo malignant transformation. Morphologic diagnosis of this spectrum of lesions is notoriously difficult, and molecular tools are increasingly used to improve diagnostic accuracy. We studied copy number aberrations in a cohort of cellular blue nevi, atypical cellular blue nevi, and melanomas ex blue nevi using Affymetrix's OncoScan platform. Cases with sufficient DNA were analyzed for GNAQ, GNA11, and HRAS mutations. Copy number aberrations were detected in 0 of 5 (0%) cellular blue nevi, 3 of 12 (25%) atypical cellular blue nevi, and 6 of 9 (67%) melanomas ex blue nevi. None of the atypical cellular blue nevi displayed more than one aberration, whereas complex aberrations involving four or more regions were seen exclusively in melanomas ex blue nevi. Gains and losses of entire chromosomal arms were identified in four of five melanomas ex blue nevi with copy number aberrations. In particular, gains of 1q, 4p, 6p, and 8q, and losses of 1p and 4q were each found in at least two melanomas. Whole chromosome aberrations were also common, and represented the sole finding in one atypical cellular blue nevus. When seen in melanomas, however, whole chromosome aberrations were invariably accompanied by partial aberrations of other chromosomes. Three melanomas ex blue nevi harbored aberrations, which were absent or negligible in their precursor components, suggesting progression in tumor biology. Gene mutations involving GNAQ and GNA11 were each detected in two of eight melanomas ex blue nevi. In conclusion, copy number aberrations are more common and often complex in melanomas ex blue nevi compared with cellular and atypical cellular blue nevi. Identification of recurrent gains and losses of entire chromosomal arms in melanomas ex blue nevi suggests that development of new probes targeting these regions may improve detection and risk stratification of these lesions.
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http://dx.doi.org/10.1038/modpathol.2015.153DOI Listing
March 2016

Dermatofibrosarcoma Protuberans in a Patient With Cowden Syndrome: Revisiting the PTEN and PDGF Pathways.

Am J Dermatopathol 2016 Apr;38(4):e40-3

*Department of Dermatology, University of Michigan, Ann Arbor, MI; †Department of Pathology, University of Chicago, Chicago, IL; ‡Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and §Department of Pathology, University of Michigan, Ann Arbor, MI.

PTEN hamartoma tumor syndrome, of which Cowden syndrome (CS) is the most recognized variant, is characterized by multiple benign and malignant tumors of ectodermal, mesodermal, and endodermal origins, secondary to germline mutation in the phosphatase and tensin homolog (PTEN) gene. Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive malignant fibroblastic/myofibroblastic tumor of the skin, characterized by the t(17:22)(q22:q13) translocation resulting in fusion of the COL1A1 and PDGFB genes. An association between CS and DFSP has not been reported in the literature to date. The authors have encountered a male patient with CS and a history of DFSP that developed adjacent to a sclerotic fibroma on the parietal scalp, both excised at age 7. He presented at age 21 with an enlarging pink nodule at the same site on the parietal scalp. Excision revealed a dermal and subcutaneous storiform spindle cell proliferation with fat entrapment and positive staining for CD34, consistent with DFSP. Fluorescence in situ hybridization confirmed PDGFB gene rearrangement. PTEN expression in the patient's recurrent DFSP was nearly absent when compared with that of sporadic DFSP. To our knowledge, this is the first report of DFSP in a patient with CS. Although the association is likely to be coincidental, the authors revisited the PTEN and the PDGF pathways to speculate any possible interplay of the 2 conditions on a molecular level.
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http://dx.doi.org/10.1097/DAD.0000000000000450DOI Listing
April 2016

Vulvar dermatoses: a histopathologic review and classification of 183 cases.

J Cutan Pathol 2015 Aug 25;42(8):510-8. Epub 2015 Jun 25.

Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

Background: Vulvar dermatoses are often difficult to classify due to histopathologic overlap. We aimed to report our experience at a single institution.

Methods: A total of 183 non-neoplastic, non-infectious vulvar biopsies were reviewed. Associations between histopathologic features and specific diagnoses were analyzed by Chi-squared tests.

Results: Twenty-two biopsies (12.0%) showed two concurrent processes. A limited differential rather than a definitive diagnosis was rendered in 15 cases (8.2%). The final diagnoses included lichen sclerosus (LS) (38.8%), lichen simplex chronicus (LSC) (29.0%), eczematous dermatitis (23.0%), Zoon vulvitis (8.2%), non-specific/resolved dermatitis (5.5%), hidradenitis suppurativa (2.7%), Behçet disease (2.2%), lichen planus (1.6%), ruptured cyst (1.6%), ulcer not-otherwise-specified (1.6%), psoriasis (1.1%), radiation dermatitis (1.1%), sebopsoriasis (1.1%), seborrheic dermatitis (1.1%), epidermolytic hyperkeratosis (0.5%) and granular parakeratosis (0.5%). Early LS and Zoon vulvitis were commonly included as part of a differential diagnosis. LS was associated with wiry collagen with lymphocyte entrapment (p = 0.0188). LSC was associated with zones of pale epithelium (p = 0.0084), and often displayed prominent fibroblasts (p = 0.0555). Zoon vulvitis was frequently misdiagnosed, and was associated with basal keratinocytic crowding (p < 0.0001).

Conclusions: Our study has determined the relative frequencies of a wide variety of vulvar dermatoses, and identified new diagnostic clues for early LS, LSC and Zoon vulvitis.
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http://dx.doi.org/10.1111/cup.12541DOI Listing
August 2015

Specificity of dermal mucin in the diagnosis of lupus erythematosus: comparison with other dermatitides and normal skin.

J Cutan Pathol 2015 Oct 21;42(10):722-9. Epub 2015 May 21.

Department of Pathology, University of Michigan, Ann Arbor, MI, USA.

Increased dermal mucin is a feature of lupus erythematosus (LE); however, its amount and distribution have not been well characterized. The differentiation of LE from other forms of dermatitis can be challenging when other features of LE are subtle or equivocal. One hundred and thirty-five skin specimens showing LE, graft vs. host disease, erythema multiforme/fixed drug eruption, lichen planus, polymorphous light eruption (PMLE), urticaria, eczematous dermatitis and psoriasis and normal skin with and without photodamage were collected. The amounts of mucin in the papillary, superficial reticular and deep reticular dermis were scored from 0 to 3 on hematoxylin-eosin (H&E) and alcian blue (AB) stains, and compared between groups. The mean scores in the reticular dermis were significantly higher in LE than in other categories except PMLE and eczematous dermatitis. A combined H&E + AB score of ≥5 in the superficial reticular dermis gave an overall specificity of 85.7% for LE. Mucin in the papillary dermis failed to distinguish among entities. Normal photodamaged skin showed significantly more mucin in the superficial reticular dermis compared to non-photodamaged skin. While LE is associated with increased mucin deposition, scant to moderate amount of mucin alone has limited specificity and is common in other dermatitides or photodamaged skin.
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http://dx.doi.org/10.1111/cup.12504DOI Listing
October 2015

Primary cutaneous cribriform carcinoma: report of six cases with clinicopathologic data and immunohistochemical profile.

J Cutan Pathol 2015 Jun 26;42(6):379-87. Epub 2015 Mar 26.

Department of Pathology, University of Michigan, Ann Arbor, MI, USA.

Background: Primary cutaneous cribriform carcinoma (PCCC) is a rare and under-recognized variant of sweat gland carcinoma, characterized by anastomosing tubules and solid nests producing a sieve-like appearance.

Methods: Six cases of PCCC were clinically, histopathologically and immunophenotypically studied.

Results: All cases showed an unencapsulated, nodular dermal tumor composed of solid and cribriform nests, cords and tubules embedded within a desmoplastic stroma. Some tubules showed micropapillary projections reminiscent of tubular adenoma, and intraluminal thin bridges resembling adenomatoid tumor. One case showed a predominantly solid component. Only two cases showed very focal decapitation secretion. Tumor cells expressed CK7, CK5/6, EMA, CEA, S-100, BerEP4 and c-kit and were negative for cytokeratin 20, estrogen receptor/progesterone receptor (ER/PR), androgen receptor and GCDFP-15. Calponin, p63 and smooth muscle actin (SMA) showed absence of a myoepithelial layer.

Conclusions: Contrary to the original reports, our series shows that PCCC may be predominantly solid with only a minor cribriform component, and expresses c-kit and S-100 which may potentially lead to the misdiagnosis of adenoid cystic carcinoma. Immunohistochemical stains may aid in distinction from tubular adenoma. Current data suggest a favorable outcome, as metastatic disease has not been reported to date.
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http://dx.doi.org/10.1111/cup.12469DOI Listing
June 2015

Neutrophilic panniculitis: algorithmic approach to a heterogeneous group of disorders.

Authors:
May P Chan

Arch Pathol Lab Med 2014 Oct;138(10):1337-43

From the Department of Pathology, University of Michigan, Ann Arbor.

Context: Neutrophilic panniculitis encompasses an etiologically and morphologically heterogeneous group of disorders. Correct histopathologic diagnosis is important in identifying certain systemic diseases and guiding appropriate treatment.

Objective: To review the clinical and histopathologic features of different types of neutrophilic panniculitis, and to provide a diagnostic algorithm for these disorders.

Data Sources: A review of the literature with emphasis on the distinguishing features of different entities was performed.

Conclusions: Evaluation for neutrophilic panniculitis entails paying close attention to the pattern of inflammation, the type of fat necrosis present, any evidence of vascular damage, and other relevant histopathologic features. An algorithmic approach integrating all histopathologic, clinical, and laboratory findings is required for correct diagnosis.
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http://dx.doi.org/10.5858/arpa.2014-0270-CCDOI Listing
October 2014

Atypical umbilical naevi: histopathological analysis of 20 cases.

Histopathology 2015 Feb 22;66(3):363-9. Epub 2014 Dec 22.

Department of Pathology, University of Michigan, Ann Arbor, MI, USA.

Aims: Melanocytic naevi on the umbilicus have been described as a form of flexural naevi, with the most common feature being a 'nested and dyshesive pattern'. We have encountered a distinct group of umbilical naevi with more significant atypia and prominent fibrosis, not reported previously. This study aimed to characterize these naevi more clearly.

Methods And Results: Eighty-one umbilical naevi from 2000 to 2013 were reviewed retrospectively, 20 cases of which showed lamellar fibrosis and atypia and were designated as atypical umbilical naevi (AUN). Lamellar fibrosis in AUN was extensive and frequently entrapped dermal melanocytes, resulting in low-grade cytological atypia (74% of cases) and impaired maturation (47%) of the dermal component. Other common features included bridging (95%), shoulder architecture (94%), lentiginous growth (85%) and high-grade junctional cytological atypia (85%). 'Nested and dyshesive pattern' was observed in only 20% of AUN. Ki-67 immunostaining performed on 12 AUN revealed a consistently low proliferation index of <1%. All AUN in this series lacked junctional confluence, florid pagetoid spread and dermal mitoses.

Conclusion: A subset of special site naevi in the umbilical region demonstrate characteristic lamellar fibrosis, architectural disorder and cytological atypia. Familiarity with these site-related atypical features would avoid overdiagnosis of melanoma.
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http://dx.doi.org/10.1111/his.12503DOI Listing
February 2015
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