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Article ; Online: Utility of sequencing for ATP6AP1 and ATP6AP2 to distinguish between atypical granular cell tumor with junctional component and melanoma.

Warren, Simon J / Alomari, Ahmed K

2023 Volume 50, Issue 11, Page(s) 1014–1019

Abstract: Background: Granular cell tumor (GCT) is a S100+ neoplasm with atypical and malignant variants. Similar to melanocytic neoplasms, the tumors make nests and can have junctional components raising a differential diagnosis of melanoma. Nevi and melanomas ... ...

Abstract	Background: Granular cell tumor (GCT) is a S100+ neoplasm with atypical and malignant variants. Similar to melanocytic neoplasms, the tumors make nests and can have junctional components raising a differential diagnosis of melanoma. Nevi and melanomas may also have granular cell cytoplasm. MelanA is useful in distinguishing melanocytic from granular cell lineage, but increasingly MelanA/SOX10 negative melanomas have been recognized by correlation with molecular methods. Methods: We encountered several cases with morphologic overlap between melanoma and atypical GCT necessitating additional molecular workup. We sequenced two cases and searched our archive for similar cases of GCT with overlapping features of melanocytic lineage. Results: In our two index cases, we excluded melanoma driver mutations and identified frameshift or premature stop codons in ATP6AP1/2 pathognomonic of granular cell lineage. Data retrieved from Cosmic identified 24 melanomas with missense single nucleotide variants (SNVs) in ATP6AP1 but no frameshift or premature stop codons. Twenty-one melanomas had missense SNVs in ATP6AP2. One melanoma had a premature stop codon in ATP6AP2, but this lesion also had a melanoma-associated driver mutation NRASQ61K. We found 1 of 23 additional cases of GCT in our archives with a junctional component and no additional cases with maturation. Conclusions: Atypical and malignant GCT can have histopathologic overlap with melanoma. Frameshift and premature stop codons in ATP6AP1/2 are specific for granular cell lineage, and capable of excluding melanoma, in the absence of known melanoma-associated driver mutations.
Language	English
Publishing date	2023-08-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	187078-6
ISSN	1600-0560 ; 0303-6987
ISSN (online)	1600-0560
ISSN	0303-6987
DOI	10.1111/cup.14503
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Article ; Online: How We Do It: Ad Hoc Immunohistochemistry for Challenging Mohs Cases.

Merkel, Emily A / Alomari, Ahmed K / Somani, Ally-Khan

Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.

2023 Volume 50, Issue 1, Page(s) 100–101

MeSH term(s)	Humans ; Immunohistochemistry ; Skin Neoplasms/diagnosis ; Skin Neoplasms/surgery ; Carcinoma, Basal Cell/surgery ; Mohs Surgery
Language	English
Publishing date	2023-09-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	1227586-4
ISSN	1524-4725 ; 1076-0512
ISSN (online)	1524-4725
ISSN	1076-0512
DOI	10.1097/DSS.0000000000003947
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Article ; Online: Lymphedematous Fibroepithelial Polyp Without Associated Condom Catheter Use: A Case Report With Review of the Literature.

Zeches, Breann A / Maher, Mohamed / Alomari, Ahmed K

The American Journal of dermatopathology

2023 Volume 45, Issue 7, Page(s) 466–469

Abstract: Abstract: Lymphedematous fibroepithelial polyps are rare proliferations involving the glans penis typically associated with chronic condom catheter usage. To the best of our knowledge, less than 20 cases have been reported in the literature with ... ...

Abstract	Abstract: Lymphedematous fibroepithelial polyps are rare proliferations involving the glans penis typically associated with chronic condom catheter usage. To the best of our knowledge, less than 20 cases have been reported in the literature with relatively similar clinical presentation. Herein, we report a case of lymphedematous fibroepithelial polyp not associated with condom usage in a 74-year-old man treated with surgical excision. On histopathological examination, the lesion displayed a hypocellular proliferation of spindled and stellate fibroblasts with intermixed Touton-like giant cells embedded within an edematous stroma with thickened vasculature. Immunohistochemical profiling exhibits strong immunoreactivity for smooth muscle actin, weak positivity for factor XIIIa, and no reactivity for CD34 or desmin. We also conducted a review of the reported range of clinical and histopathological features of this entity in addition to the various hypotheses regarding its pathogenesis. We hope to increase awareness and accurate diagnosis of this entity, which could affect clinical management.
MeSH term(s)	Male ; Humans ; Aged ; Condoms/adverse effects ; Polyps/etiology ; Polyps/surgery ; Penis/pathology ; Skin Neoplasms/pathology ; Catheters/adverse effects ; Lymphedema/pathology
Language	English
Publishing date	2023-05-29
Publishing country	United States
Document type	Review ; Case Reports ; Journal Article
ZDB-ID	448469-1
ISSN	1533-0311 ; 0193-1091
ISSN (online)	1533-0311
ISSN	0193-1091
DOI	10.1097/DAD.0000000000002462
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Article: The new and old in superficial mesenchymal tumors with uncertain origin and/or melanocytic differentiation.

Alkashash, Ahmad / Samiei, Azadeh / Alomari, Ahmed K

Seminars in diagnostic pathology

2023 Volume 40, Issue 4, Page(s) 258–266

MeSH term(s)	Humans ; Melanoma/pathology ; Skin Neoplasms/pathology ; Neoplasms, Connective and Soft Tissue
Language	English
Publishing date	2023-04-25
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	605834-6
ISSN	1930-1111 ; 0740-2570
ISSN (online)	1930-1111
ISSN	0740-2570
DOI	10.1053/j.semdp.2023.04.013
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Article ; Online: MAP2K1-mutated melanocytic tumors have reproducible histopathologic features and share similarities with melanocytic tumors with BRAF V600E mutations.

Alomari, Ahmed K / Harms, Paul W / Andea, Aleodor A / Warren, Simon J

Journal of cutaneous pathology

2023 Volume 50, Issue 12, Page(s) 1083–1093

Abstract: Background: Melanocytic tumors driven by MAP2K1 in-frame deletions are among the most recently described class of melanocytic neoplasms. The reported range of diagnoses and associated genomic aberrations in these neoplasms is wide and includes melanomas, ...

Abstract	Background: Melanocytic tumors driven by MAP2K1 in-frame deletions are among the most recently described class of melanocytic neoplasms. The reported range of diagnoses and associated genomic aberrations in these neoplasms is wide and includes melanomas, deep penetrating melanocytomas, and pigmented epithelioid melanocytoma. However, little is known about the characteristics of these tumors, especially in the absence of well-known second molecular "hits." Moreover, despite their frequent spitzoid cytomorphology, their potential categorization among the Spitz tumors is debatable. Materials and methods: We conducted a retrospective search through our molecular archives to identify sequenced melanocytic tumors with MAP2K1 in-frame deletions. We reviewed the clinical and histomorphological features of these tumors and compared them to similar neoplasms reported to date. In addition, we performed single-nucleotide polymorphism (SNP) array testing to identify structural chromosomal aberrations. Results: Of 27 sequenced tumors, 6 (22%) showed a pathogenic MAP2K1 in-frame deletion (with or without insertion) and were included in this series. Five (83%) were females with lesions involving the upper limb. Histopathologically, all neoplasms were compounded with plaque-like or wedge-shaped silhouettes, spitzoid cytomorphology, and impaired cytologic maturation. All cases showed background actinic damage with sclerotic stroma replacing solar elastosis, variable pagetoid scatter, and occasional dermal mitotic figures (range 1-2/mm Discussion and conclusion: Melanocytic tumors with MAP2K1 in-frame deletion could represent another spectrum of melanocytic tumors with close genotypic-phenotypic correlation. They are largely characterized by a spectrum that encompasses desmoplastic Spitz nevus as shown in our series and Spitz and Clark nevus as shown by others. Evolutionary, they share many similarities with tumors with BRAF V600E mutations, suggesting they are better classified along the conventional pathway rather than the Spitz pathway despite the frequent spitzoid morphology.
MeSH term(s)	Female ; Humans ; Male ; Proto-Oncogene Proteins B-raf/genetics ; Retrospective Studies ; Ultraviolet Rays ; Melanoma/pathology ; Skin Neoplasms/pathology ; Nevus, Epithelioid and Spindle Cell/genetics ; Chromosome Aberrations ; MAP Kinase Kinase 1/genetics
Chemical Substances	Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; BRAF protein, human (EC 2.7.11.1) ; MAP2K1 protein, human (EC 2.7.12.2) ; MAP Kinase Kinase 1 (EC 2.7.12.2)
Language	English
Publishing date	2023-08-11
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	187078-6
ISSN	1600-0560 ; 0303-6987
ISSN (online)	1600-0560
ISSN	0303-6987
DOI	10.1111/cup.14502
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Article ; Online: A Rare Case of Myxochondroid Metaplasia of the Plantar Foot With Review of Histopathological Mimics.

Alomari, Ahmed K / Warnock, Aaron / Cummings, Oscar W

The American Journal of dermatopathology

2022 Volume 44, Issue 10, Page(s) e113–e116

Abstract: Abstract: Chondromyxoid metaplasia can rarely lead to the formation of a distinctive tumor-like proliferation in the plantar foot. This is thought to represent a reactive or reparative process, possibly due to chronic trauma. For the unwary ... ...

Abstract	Abstract: Chondromyxoid metaplasia can rarely lead to the formation of a distinctive tumor-like proliferation in the plantar foot. This is thought to represent a reactive or reparative process, possibly due to chronic trauma. For the unwary dermatopathologist, this could represent a diagnostic challenge. Herein, we review the clinical, histopathological, and molecular presentation of an athletic 17-year-old boy with a soft tissue mass arising in the right plantar foot. Microscopic examination showed a relatively circumscribed proliferation of spindle cells with abundant chondromyxoid stroma, hyalinization, and diffuse ERG reactivity. We also review characteristics of this entity that help differentiate it from clinical and histopathologic mimics and postulate possible links with soft tissue chondromas and immature chondroid choristoma.
MeSH term(s)	Adolescent ; Chondroma ; Foot Diseases/diagnosis ; Humans ; Male ; Metaplasia ; Soft Tissue Neoplasms
Language	English
Publishing date	2022-04-27
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	448469-1
ISSN	1533-0311 ; 0193-1091
ISSN (online)	1533-0311
ISSN	0193-1091
DOI	10.1097/DAD.0000000000002214
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Article: Predicting melanoma survival and metastasis with interpretable histopathological features and machine learning models.

Couetil, Justin / Liu, Ziyu / Huang, Kun / Zhang, Jie / Alomari, Ahmed K

Frontiers in medicine

2023 Volume 9, Page(s) 1029227

Abstract: Introduction: Melanoma is the fifth most common cancer in US, and the incidence is increasing 1.4% annually. The overall survival rate for early-stage disease is 99.4%. However, melanoma can recur years later (in the same region of the body or as ... ...

Abstract	Introduction: Melanoma is the fifth most common cancer in US, and the incidence is increasing 1.4% annually. The overall survival rate for early-stage disease is 99.4%. However, melanoma can recur years later (in the same region of the body or as distant metastasis), and results in a dramatically lower survival rate. Currently there is no reliable method to predict tumor recurrence and metastasis on early primary tumor histological images. Methods: To identify rapid, accurate, and cost-effective predictors of metastasis and survival, in this work, we applied various interpretable machine learning approaches to analyze melanoma histopathological H&E images. The result is a set of image features that can help clinicians identify high-risk-of-metastasis patients for increased clinical follow-up and precision treatment. We use simple models (i.e., logarithmic classification and KNN) and "human-interpretable" measures of cell morphology and tissue architecture (e.g., cell size, staining intensity, and cell density) to predict the melanoma survival on public and local Stage I-III cohorts as well as the metastasis risk on a local cohort. Results: We use penalized survival regression to limit features available to downstream classifiers and investigate the utility of convolutional neural networks in isolating tumor regions to focus morphology extraction on only the tumor region. This approach allows us to predict survival and metastasis with a maximum F1 score of 0.72 and 0.73, respectively, and to visualize several high-risk cell morphologies. Discussion: This lays the foundation for future work, which will focus on using our interpretable pipeline to predict metastasis in Stage I & II melanoma.
Language	English
Publishing date	2023-01-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2022.1029227
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Article ; Online: Primary mucoepidermoid carcinoma of the external auditory canal with a CRTC1::MAML2 fusion: A case report and a review of literature.

De la Sancha, Carlo / Kuhar, Matthew / Kraft, Adele / Alomari, Ahmed K

Journal of cutaneous pathology

2023 Volume 50, Issue 11, Page(s) 947–950

Abstract: Mucoepidermoid carcinoma is a malignant neoplasm of exocrine glands that arises predominantly in salivary glands. It is seldom encountered as a primary cutaneous neoplasm, and in those patients, it often involves the external auditory canal. Given their ... ...

Abstract	Mucoepidermoid carcinoma is a malignant neoplasm of exocrine glands that arises predominantly in salivary glands. It is seldom encountered as a primary cutaneous neoplasm, and in those patients, it often involves the external auditory canal. Given their rarity, they can pose a diagnostic challenge and prompt extensive workup. In salivary glands, mucoepidermoid carcinomas commonly harbor CRTC1/3::MAML2 fusions; however, genetic alterations of primary cutaneous neoplasms are less characterized, with previous studies reporting CRTC1 rearrangements in the absence of MAML2 aberrations. Herein, we report a case of a primary cutaneous mucoepidermoid carcinoma of the external auditory canal with a CRTC1::MAML2 rearrangement. We also review the clinical, morphologic, and molecular features of this neoplasm and compare them to those reported in the literature and to histopathologic mimics.
MeSH term(s)	Humans ; DNA-Binding Proteins/genetics ; Carcinoma, Mucoepidermoid/genetics ; Carcinoma, Mucoepidermoid/pathology ; Trans-Activators/genetics ; Ear Canal/pathology ; Nuclear Proteins/genetics ; Transcription Factors/genetics ; Skin Neoplasms/genetics ; Oncogene Proteins, Fusion/genetics ; Salivary Gland Neoplasms/genetics
Chemical Substances	DNA-Binding Proteins ; Trans-Activators ; Nuclear Proteins ; Transcription Factors ; Oncogene Proteins, Fusion ; MAML2 protein, human ; CRTC1 protein, human
Language	English
Publishing date	2023-07-02
Publishing country	United States
Document type	Review ; Case Reports
ZDB-ID	187078-6
ISSN	1600-0560 ; 0303-6987
ISSN (online)	1600-0560
ISSN	0303-6987
DOI	10.1111/cup.14491
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Article ; Online: Detection of Gene Mutations in Liquid Biopsy of Melanoma Patients: Overview and Future Perspectives.

Alrabadi, Nasr / Haddad, Razan / Alomari, Ahmed K

Current treatment options in oncology

2020 Volume 21, Issue 3, Page(s) 19

Abstract: Opinion statement: Liquid biopsies are still far from widely implanted in the clinical arena. Issues related to the added sensitivity of this test beyond conventional methods have not been fully resolved. Additionally, issues related to the specificity ... ...

Abstract	Opinion statement: Liquid biopsies are still far from widely implanted in the clinical arena. Issues related to the added sensitivity of this test beyond conventional methods have not been fully resolved. Additionally, issues related to the specificity of these results especially as many cancers may share common mutation need further investigations. One way to resolve this may include the development and testing of large gene panels to add higher specificity. On the other hand, further studies are needed to support the idea that ctDNA or circulating tumor cells may constitute a better representation of the tumor subpopulation that is capable of metastasizing, which will strongly support its clinical value. Finally, survival studies showing a positive impact of this technology will also justify its widespread implementation in clinical practice.
MeSH term(s)	Biomarkers, Tumor ; Circulating Tumor DNA ; Genetic Association Studies ; Genetic Predisposition to Disease ; Humans ; Liquid Biopsy/methods ; Melanoma/diagnosis ; Melanoma/genetics ; Mutation ; Neoplastic Cells, Circulating
Chemical Substances	Biomarkers, Tumor ; Circulating Tumor DNA
Language	English
Publishing date	2020-02-11
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2057351-0
ISSN	1534-6277 ; 1527-2729
ISSN (online)	1534-6277
ISSN	1527-2729
DOI	10.1007/s11864-020-0708-4
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Article ; Online: Extranodal NK/T-cell lymphoma primarily presenting as two adjacent slowly growing skin nodules with prominent epidermotropism and CD30 expression, a case report and review of literature.

Mohammed, Arooj / Dave, Utpal / Ms, Sahand Rahnama-Moghadam / Alomari, Ahmed K

Dermatology online journal

2021 Volume 27, Issue 12

Abstract: Extranodal NK/T-cell lymphoma (NKTCL) is a rarely occurring non-Hodgkin lymphoma with predilection for the nasal cavity. Cutaneous involvement, rarely occurring and often aggressive in behavior, may present as nodular mass-forming lesions with or without ...

Abstract	Extranodal NK/T-cell lymphoma (NKTCL) is a rarely occurring non-Hodgkin lymphoma with predilection for the nasal cavity. Cutaneous involvement, rarely occurring and often aggressive in behavior, may present as nodular mass-forming lesions with or without ulceration. Histologically, lesions are characterized by an atypical dermal lymphoid infiltrate with angioinvasion and associated necrosis. Fortuitously, Epstein-Barr virus (EBV) infection, implicated in the pathogenesis of this entity, serves as a useful diagnostic marker (i.e. EBER in situ hybridization). We present a 54-year-old-man who initially presented with two ulcerations on the right lower leg which progressed despite antibiotic therapy. Histologic examination demonstrated dense lymphoid infiltrates exhibiting epidermotropism, angiocentricity and angioinvasion extending into the deep dermis. Immunohistochemical staining demonstrated expression of CD2, CD3, CD8, TIA-1, perforin, and granzyme-B, consistent with a cytotoxic T-cell phenotype. Additionally, CD56 was positive, confirming the presence of a coexistent NK cell phenotype. Testing also demonstrated significant CD30 expression, and molecular analysis was positive for TCR gene rearrangement. These findings, in conjunction with EBER in situ hybridization positivity, confirmed a diagnosis of extranodal NKTCL. We aim to increase awareness of this rarely occurring lymphoma with cutaneous involvement. CD30 expression in NKTCL raises the possibility of targeted treatment with brentuximab.
MeSH term(s)	Epstein-Barr Virus Infections/complications ; Herpesvirus 4, Human ; Humans ; Ki-1 Antigen ; Lymphoma, Extranodal NK-T-Cell/diagnosis ; Lymphoma, Extranodal NK-T-Cell/genetics ; Lymphoma, Extranodal NK-T-Cell/pathology ; Skin Neoplasms/pathology
Chemical Substances	Ki-1 Antigen
Language	English
Publishing date	2021-12-15
Publishing country	United States
Document type	Case Reports ; Journal Article ; Review
ZDB-ID	2026239-5
ISSN	1087-2108 ; 1087-2108
ISSN (online)	1087-2108
ISSN	1087-2108
DOI	10.5070/D3271256701
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