Macrophages play essential roles in maintaining tissue homeostasis and immune defence. However, their extensive infiltration into tumours has been linked to adverse outcomes in multiple human cancers. Within the tumour microenvironment (TME), tumour-associated macrophages (TAMs) promote tumour growth and metastasis, making them prime targets for cancer immunotherapy. Recent single-cell analysis suggest that proliferating TAMs accumulate in human cancers, yet their origins and differentiation pathways remain uncertain. Here, we show that a subpopulation of CD163+ TAMs proliferates in situ within the TME of melanoma, lung cancer, and breast cancer. Consistent with their potential role in suppressing anti-tumour activities of T cells, CD163+ TAMs express a range of potent immunosuppressive molecules, including PD-L1, PD-L2, IL-10, and TGF-β. Other phenotypic markers strongly suggested that these cells originate from CD14+ CCR2+ monocytes, a cell population believed to have minimal capacity for proliferation. However, we demonstrate in vitro that certain myelopoietic cytokines commonly available within the TME induce robust proliferation of human monocytes, especially the combination of interleukin 3 (IL-3) and Macrophage Colony-Stimulating Factor 1 (M-CSF). Monocytic cells cultured with these cytokines efficiently modulate T cell proliferation, and their molecular phenotype recapitulates that of CD163+ TAMs. IL-3-driven proliferation of monocytic cells can be completely blocked by IL-4, associated with the induction of CDKN1A, alongside the upregulation of transcription factors linked to dendritic cell function, such as BATF3 and IRF4. Taken together, our work suggests several novel therapeutic routes to reducing immunosuppressive TAMs in human tumours, from blocking chemokine-mediated recruitment of monocytes to blocking their proliferation.

Thanks in large part to the invention of new technologies, teledermatopathology has gained traction as being an integral part in the practice of dermatopathology. Aside from the obvious convenience of being able to view histologic slides at remote locations, the technology offers the potential for enhancing patient care by allowing expert consultation services, increasing physician wellness, and integrating the application of diagnostic software. The cost has been a key concern in introducing digital systems into a laboratory; the introduction of billing codes and further validation with regulatory approval has improved the ability to gauge the feasibility of purchasing equipment.

There are numerous tumour types in the sweat ductoglandular appendageal group of cutaneous adnexal tumours. Nevertheless, new tumour types, including secretory carcinoma,1Kastnerova L. Luzar B. Goto K. et al.Secretory carcinoma of the skin: report of 6 cases, including a case with a novel NFIX-PKN1 translocation.Am J Surg Pathol. 2019; 43: 1092-1098Crossref PubMed Scopus (24) Google Scholar sweat-gland carcinoma with neuroendocrine differentiation,2Goto K. Kukita Y. Honma K. et al.Sweat-gland carcinoma with neuroendocrine differentiation (SCAND): a clinicopathologic study of 13 cases with genetic analysis.Mod Pathol. 2022; 35: 33-43Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar and NUT adnexal carcinoma,3Nishimura Y. Ryo E. Yamazaki N. et al.Cutaneous primary NUT carcinoma with BRD3-NUTM1 fusion.Am J Surg Pathol. 2021; 45: 1582-1584Crossref PubMed Scopus (7) Google Scholar have been recently proposed and established. Herein, we present three cases of a sweat ductal tumour with novel, characteristic histopathological features of anastomosing epithelial growth accompanied by a surrounding and intermixed lymphocytic infiltrate. This study aimed to thoroughly investigate them and illustrate why we believe that this represents a new tumour entity. The study was approved by the research ethics committee of Osaka International Cancer Institute, Osaka, Japan (reference number: 21179). Three cases (Cases 1–3) with similar histopathological features were retrieved from the author's (KG) consultation files (2020–2021). In Case 1, a subcutaneous nodule with over 20 years history was found in the right eyebrow area of a 53-year-old woman. The lesion exhibited a skin-colored appearance with a diameter of approximately 1 cm. She felt no pain. The past medical history included breast cancer (invasive ductal carcinoma) 18 months previously. The patient in Case 2 was a 41-year-old woman who had a 12 mm subcutaneous nodule on her scalp. This had been thought to be a benign cyst clinically and she remembers first noticing it 10–15 years previously. Case 3 was a 31-year-old woman who also had a 12 mm subcutaneous nodule on her scalp. This had been present for at least 5 years and she felt it had increased in size slowly over that time. In addition, 16 years had now elapsed since it was resected. All these patients have been followed clinically and none have known evidence of recurrence or metastasis to date (follow-up duration: 6 months in Case 1, 16 years in Case 2, 4 years in Case 3). The clinical courses before surgery were over 20 years in Case 1, 10–15 years in Case 2, and at least 5 years in Case 3. All tumours showed similar histopathological features (Fig. 1). They were well-circumscribed subcutaneous tumours without circumferential fibrous capsule formation (Fig. 1A,F,K). A prominent lymphoid cuff was present at the periphery of the tumours as well as prominent lymphoid stroma within the tumours (Fig. 1A,F,K). These tumours exhibited an anastomosing epithelial network (Fig. 1B,D,G,I,L,N). A few small ductal and dilated cystic structures were distributed within the tumour nests (Fig. 1B,C,G,H,L,M,N). Most inner side tumour cells had a spindled/fusiform eosinophilic cytoplasm with keratinization, similar to the squamoid changes seen in squamoid eccrine duct carcinoma. The squamoid change was seen in all cases with varying degrees, and was most prominent in Case 3 (Fig. 1L,M). The tumour cells had oval nuclei with one or two small nucleoli. Nuclear chromatin was heterogeneously distributed but not increased. No nuclear atypia was observed (Fig. 1D,E,I,J,M). Mitotic figures were not observed in the tumour cells. No peripheral palisading of the tumour cells resembling follicular germinative cells was confirmed (Fig. 1D,E,I,J,M). An infiltrate of mainly lymphocytes, with fewer plasma cells, and eosinophils was observed in the tumour stroma (Fig. 1E,H,J,M–O). The tumour stroma was fibrotic, but neither hyalinising nor sclerosing changes were noted (Fig. 1D,E,I,J,O). The immunoprofile in all cases is summarised in Table 1 [expression of all the immunohistochemical markers other than Ki-67 and YAP1 was graded into four categories: negative (−), focally positive (+, 1–30% of the targeted tumour components), partially positive (++, 31–70%), and diffusely positive (+++, 71–100%)]. The peripheral layer tumour cells expressed CK5/6 and p63 but not CK7, CK19, BerEP4, CEA, and EMA (Fig. 2A–I). In contrast, the inner side tumour cells were positive for CK7, CK19, BerEP4, CEA, and EMA but negative for CK5/6 and p63 (Fig. 2A–I). CEA and EMA also highlighted the luminal surface within the tumour nests (Fig. 2H,I). In Case 3 with marked squamoid change, the peripheral layer tumour cells expressing CK5/6 and p63 were more prominent than the inner side tumour cells expressing CK7, CK19, and BerEP4 (Fig. 2E). GATA3 expression was limited (Fig. 2J). However, CK20, c-kit, ER, GCDFP15, mammaglobin, α-SMA, SOX10, BRAF, NUT, and PLAG1 were completely negative for these tumour cells. Nuclear YAP1 immunoexpression was observed in <5% of tumour cells in two tested cases. The Ki-67 labeling index was ≤10% in all tumours (Fig. 2K). In situ hybridisation for EBER was performed in all cases, with negative results. Moreover, MAML2 break-apart FISH revealed no split signals in any case (Fig. 2L).Table 1Immunohistochemical findings of three casesCase 1Case 2Case 3CK5/6+++ (P)+++ (P)+++ (B)CK7+++ (I)+++ (I)+ (I)CK19+++ (I)+++ (I)+ (I)CK20−−−BerEP4+ (I)++ (I)+ (I)c-kit−−−CEA+++ (L), ++ (I)+++ (L), ++ (I)NDEMA++ (L), ++ (I)++ (L), ++ (I)NDER−−−GATA3++ (I)+ (I)+ (I)GCDFP15−−NDMammaglobin−−NDP63+++ (P)+++ (P)+++ (B)α-SMA−−−SOX10−−NDBRAF−−NDMYB+ (B)−−NUT−−NDPLAG1−−NDYAP1<5%<5%NDKi-6710%5%5%α-SMA, α-smooth muscle action; B, on both tumour cells; CEA, carcinoembryonic antigen; CK, cytokeratin; EMA, epithelial membrane antigen; ER, oestrogen receptor; GCDFP15, gross cystic disease fluid protein 15; I, on the inner side tumour cells; L, on the luminal surface; ND, not done; P, on the peripheral layer tumour cells; PLAG1, pleomorphic adenoma gene 1; YAP1, yes-associated protein 1. Open table in a new tab α-SMA, α-smooth muscle action; B, on both tumour cells; CEA, carcinoembryonic antigen; CK, cytokeratin; EMA, epithelial membrane antigen; ER, oestrogen receptor; GCDFP15, gross cystic disease fluid protein 15; I, on the inner side tumour cells; L, on the luminal surface; ND, not done; P, on the peripheral layer tumour cells; PLAG1, pleomorphic adenoma gene 1; YAP1, yes-associated protein 1. We present the investigation of three cases of a sweat ductal tumour with distinctive histopathological features, which to the best of our knowledge have not been previously reported. All tumours developed as a well-demarcated subcutaneous nodule on the upper part of the head in young or middle-aged women. Histopathologically, anastomosing structures composed of peripheral layer tumour cells expressing CK5/6 and p63 and inner side tumour cells expressing CK7, CK19, BerEP4, CEA, and EMA were characteristic of the tumours. Squamoid change (squamous metaplasia) was present in all cases. Intriguingly, all cases had a striking lymphocytic infiltrate which was most prominent peripherally and associated with fibrosis. These well-circumscribed tumours have no nuclear atypia and no mitotic activity. Taken together with the uneventful clinical course ranging from approximately 5 to over 20 years, a benign biological behaviour seems likely. The two population layers composed of ductoglandular and peripheral cells and ductal lumen highlighted by CEA and EMA are consonant with a sweat ductoglandular adnexal tumour rather than a follicular or sebaceous adnexal tumour. These tumours may exhibit sweat ductal differentiation, owing to the lack of a myoepithelial component implied by the lack of SOX10 and α-SMA staining, and the lack of eccrine glandular differentiation implied by the lack of SOX10.4Lezcano C. Ho J. Seethala R.R. Sox10 and DOG1 expression in primary adnexal tumors of the skin.Am J Dermatopathol. 2017; 39: 896-902Crossref PubMed Scopus (14) Google Scholar Although sweat ductal tumours are usually positive for c-kit,5Goto K. Immunohistochemistry for CD117 (KIT) is effective in distinguishing cutaneous adnexal tumors with apocrine/eccrine or sebaceous differentiation from other epithelial tumors of the skin.J Cutan Pathol. 2015; 42: 480-488Crossref PubMed Scopus (21) Google Scholar the three tumours in the present study did not express c-kit. The squamoid changes may lead to the loss of c-kit immunoexpression5Goto K. Immunohistochemistry for CD117 (KIT) is effective in distinguishing cutaneous adnexal tumors with apocrine/eccrine or sebaceous differentiation from other epithelial tumors of the skin.J Cutan Pathol. 2015; 42: 480-488Crossref PubMed Scopus (21) Google Scholar,6Goto K. Takai T. Fukumoto T. et al.CD117 (KIT) is a useful immunohistochemical marker for differentiating porocarcinoma from squamous cell carcinoma.J Cutan Pathol. 2016; 43: 219-226Crossref PubMed Scopus (28) Google Scholar and could explain this finding. The p63 positivity is interesting. Some of the positivity can be explained by the squamoid morphology, but the rimming p63-positive tumour cells have the character of poroid cells. Poroid cells, which are located outside sweat ducts, express p63 but do not express SOX10 or SMA. Given these novel findings, serious consideration was given to the differential diagnosis. Case 3 was originally biopsied in 2006 and has been seen in consultation by a variety of senior dermatopathologists who have been unable to categorise it. Squamous cell carcinoma, including lymphoepithelioma-like carcinoma of the skin, is the most important differential diagnosis; however, the present cases have ductal differentiation and lack atypia.7Requena L. Sánchez Yus E. Jiménez E. et al.Lymphoepithelioma-like carcinoma of the skin: a light-microscopic and immunohistochemical study.J Cutan Pathol. 1994; 21: 541-548Crossref PubMed Scopus (38) Google Scholar Cribriform carcinoma can also be accompanied by a lymphoid cuff but does not exhibit anastomosis of squamoid tumour cells or two population layers of p63-positive peripheral cells and p63-negative inner side cells.8Rütten A. Kutzner H. Mentzel T. et al.Primary cutaneous cribriform apocrine carcinoma: a clinicopathologic and immunohistochemical study of 26 cases of an under-recognized cutaneous adnexal neoplasm.J Am Acad Dermatol. 2009; 61: 644-651Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar Adenoid cystic carcinoma is composed of c-kit-positive ductoglandular epithelial and SOX10-positive myoepithelial cells and does not have an inflammatory stroma.9Goto K. Kajimoto K. Sugino T. et al.MYB translocations in both myoepithelial and ductoglandular epithelial cells in adenoid cystic carcinoma: a histopathologic and genetic reappraisal in six primary cutaneous cases.Am J Dermatopathol. 2021; 43: 278-283Crossref PubMed Scopus (4) Google Scholar Poroid neoplasms show proliferation of poroid cells and immunoreactivity for YAP1 and NUT, reflecting YAP1::NUT or YAP1::MAML2 fusions.10Sekine S. Kiyono T. Ryo E. et al.Recurrent YAP1-MAML2 and YAP1-NUTM1 fusions in poroma and porocarcinoma.J Clin Invest. 2019; 129: 3827-3832Crossref PubMed Scopus (100) Google Scholar Two of the three cases expressed extremely limited YAP1 expression, which does not suggest YAP1 fusion, but similar limited expression of YAP1 can be seen in the normal epidermal keratinocytes and other cancers.10Sekine S. Kiyono T. Ryo E. et al.Recurrent YAP1-MAML2 and YAP1-NUTM1 fusions in poroma and porocarcinoma.J Clin Invest. 2019; 129: 3827-3832Crossref PubMed Scopus (100) Google Scholar,11Neinaa Y.M.E. El-Aziz Mohamed D.A. Ali S.A.E. et al.YAP1 expression in lichen planus and squamous cell carcinoma: role in disease pathogenesis and potential therapeutic target.Am J Dermatopathol. 2022; 44: 348-354Crossref PubMed Scopus (2) Google Scholar Hidradenoma does not demonstrate an anastomosing/reticulated tumour structure or the lymphocytic infiltrate, and MAML2 translocation seems to be a constant feature.12Russell-Goldman E. Hanna J. MAML2 gene rearrangement occurs in nearly all hidradenomas: a reappraisal in a series of 20 cases.Am J Dermatopathol. 2022; 44: 806-811Crossref PubMed Scopus (1) Google Scholar Tubular adenoma also does not show an anastomosing/reticulated tumour structure, and the BRAF V600E mutation is frequently present in this tumour. Apocrine mixed tumour of the skin is characteristic of the proliferation of myoepithelial tumour cells with SOX10, α-SMA, and PLAG1 immunoexpression. Eccrine mixed tumour is composed of numerous small monolayered ductal structures with round lumina and myxohyalinised and cartilaginous stroma but not anastomosing ductal structures nor lymphoid stroma. Cutaneous lymphadenoma is a benign trichoblastoma-like tumour with Reed–Sternberg-like cells but does not show sweat ductoglandular differentiation. In addition, lymphoid aggregates in the tumour nests are seen in cutaneous lymphadenoma but not in our cases. All tumours in the present study were noted in the upper part of the head of young to middle-aged women, although it remains unknown whether the clinical findings are characteristic of this tumour type. Additional reports will likely further define the clinicopathological characteristics. In this study, we investigate three cases of a sweat ductal tumour with distinctive histopathological features. Based on the characteristic histopathological features, we believe these should be designated as a distinct entity and propose the label ‘anastomosing squamoid adenoma’. Hopefully, this will encourage others to identify further cases of this unusual tumour. The datasets generated and analysed during the present study are available from the corresponding author on reasonable request and IRB approval but are not publicly available due to privacy or ethical restrictions. The authors state that there are no conflicts of interest to disclose.

Background Appropriate use criteria (AUC) provide patient-centered physician guidance in test selection. An initial set of AUC was reported by the American Society of Dermatopathology (ASDP) in 2018. AUC reflect evidence collected at single timepoints and may be affected by evolving evidence and experience. The objective of this study was to update and expand AUC for selected tests. Methods RAND/UCLA (RAND Corporation [Santa Monica, CA]/University of California Los Angeles) methodology used includes the following: (a) literature review; (b) review of previously rated tests and previously employed clinical scenarios; (c) selection of previously rated tests for new ratings; (d) development of new clinical scenarios; (e) selection of additional tests; (f) three rating rounds with feedback and group discussion after rounds 1 and 2. Results For 220 clinical scenarios comprising lymphoproliferative (light chain clonality), melanocytic (comparative genomic hybridization, fluorescence in situ hybridization, reverse transcription polymerase chain reaction, telomerase reverse transcriptase promoter), vascular disorders (MYC), and inflammatory dermatoses (periodic acid-Schiff, Gomori methenamine silver), consensus by panel raters was reached in 172 of 220 (78%) scenarios, with 103 of 148 (70%) rated "usually appropriate" or "rarely appropriate" and 45 of 148 (30%), "appropriateness uncertain." Limitations: The study design only measures appropriateness. Cost, availability, test comparison, and additional clinical considerations are not measured. The possibility that the findings of this study may be influenced by the inherent biases of the dermatopathologists involved in the study cannot be excluded. Conclusions AUC are reported for selected diagnostic tests in clinical scenarios that occur in dermatopathology practice. Adhering to AUC may reduce inappropriate test utilization and improve healthcare delivery.

BACKGROUND:Achieving negative margins for melanoma in situ, lentigo maligna type can be challenging, particularly on cosmetically sensitive areas.OBJECTIVE:To assess the utility of intraoperative frozen section margin assessment using a teledermatopathology system in the treatment of head and neck lentigo maligna.METHODS AND MATERIALS:Over a 6 year period, 96 patients with lentigo maligna had surgical excisions. The margins were assessed intraoperatively with frozen sections prepared in the manner used in Mohs surgery. The surgeon guided the frozen section slides around the margin while a dermatopathologist assessed the margin remotely.RESULTS:In 2/96 (2.1%) cases, the safety margin was positive (frozen sections were false negative). In 1 further case (1%) there was a recurrence of the melanoma 13 months following the excision.CONCLUSION:The described method is effective in treating melanoma in situ, lentigo maligna type with clearance rates similar to previous studies for Mohs surgery.

Background and objective Located on chromosome locus 5p15.33, telomerase reverse transcriptase (TERT or hTERT) encodes the catalytic subunit of telomerase which permits lengthening and preservation of telomeres following mitosis. Mutations in TERT promoter (TERT-p) upregulate expression of TERT, allowing survival of malignant cells and tumor progression in wide variety of malignancies including melanoma. The objective of this review is to examine the roles of TERT and TERT-p in the pathogenesis, diagnosis, and prognostication of cutaneous melanoma. Methods All studies of TERT or TERT-p in cutaneous melanocytic neoplasms with the following inclusion criteria were reviewed: publication date between 2010 and 2019, English language, and series of >= 3 cases were reviewed for evidence supporting the role of TERT in pathogenesis, diagnosis, and prognosis. Studies with TERT-p mutations are frequent in chronic and non-chronic sun damage melanoma and correlate with adverse prognosis, inform pathogenesis, and may provide diagnostic support. While TERT-p mutations are uncommon in acral melanoma, TERT copy number gains and gene amplification predict reduced survival. Among atypical spitzoid neoplasms, TERT-p mutations identify biologically aggressive tumors and support the diagnosis of spitzoid melanoma. TERT-p methylation may have prognostic value in pediatric conventional melanoma and drive tumorigenesis in melanoma arising within congenital nevi. Finally, TERT-p mutations may aid in the differentiation of recurrent nevi from recurrent melanoma.

Background Muir-Torre syndrome (MTS) is a rare inherited syndrome, with an increased risk of sebaceous and visceral malignancy. Prior reports suggest screening for mismatch repair (MMR) deficiency may be warranted in patients <50 years and when sebaceous neoplasms are located on a non-head and neck location. Previously, appropriate use criteria (AUC) were developed for clinical scenarios in patients >60 years concerning the use of MMR protein immunohistochemistry (MMRP-IHC). This analysis explores the appropriateness of testing in patients <= 60 years. Methods Panel raters from the AUC Task Force rated the use of MMRP-IHC testing for MTS for previously rated scenarios with the only difference being age. Results Results verify the previously developed AUC for the use of MMRP-IHC in neoplasms associated with MTS in patients >60 years. Results also show that in patients <= 60 years with a single sebaceous tumor on a non-head and neck site, MMRP-IHC testing should be considered. Testing can also be considered with a 2-antibody panel on periocular sebaceous carcinoma in younger patients. Conclusions Our findings align with known evidence supporting the need to incorporate clinical parameters in identifying patients at risk for MTS, with age being a factor when considering MMRP-IHC testing.

ANZ Journal of SurgeryVolume 89, Issue 7-8 p. 982-983 LETTER TO THE EDITOR Use of dynamic telepathology utilizing a smartphone in margin control cutaneous surgery Patrick Emanuel MBChB, FRCPA, Corresponding Author Patrick Emanuel MBChB, FRCPA paddyemanuel@gmail.com orcid.org/0000-0003-1068-6969 Division of Dermatopathology, Mount Sinai Medical Center, New York, New York, USASearch for more papers by this authorRajan Patel MBChB, FRACS, Rajan Patel MBChB, FRACS Skin Institute, Auckland, New ZealandSearch for more papers by this authorStephanie Liu DO, Stephanie Liu DO Division of Dermatopathology, Mount Sinai Medical Center, New York, New York, USASearch for more papers by this authorMatthew Goldberg MD, FAAD, Matthew Goldberg MD, FAAD Division of Dermatopathology, Mount Sinai Medical Center, New York, New York, USASearch for more papers by this authorErika Romero Sandoval MD, Erika Romero Sandoval MD Hospital Nacional Cayetano Heredia, Lima, PeruSearch for more papers by this authorMark Izzard MBBS, FRACS, Mark Izzard MBBS, FRACS Skin Institute, Auckland, New ZealandSearch for more papers by this author Patrick Emanuel MBChB, FRCPA, Corresponding Author Patrick Emanuel MBChB, FRCPA paddyemanuel@gmail.com orcid.org/0000-0003-1068-6969 Division of Dermatopathology, Mount Sinai Medical Center, New York, New York, USASearch for more papers by this authorRajan Patel MBChB, FRACS, Rajan Patel MBChB, FRACS Skin Institute, Auckland, New ZealandSearch for more papers by this authorStephanie Liu DO, Stephanie Liu DO Division of Dermatopathology, Mount Sinai Medical Center, New York, New York, USASearch for more papers by this authorMatthew Goldberg MD, FAAD, Matthew Goldberg MD, FAAD Division of Dermatopathology, Mount Sinai Medical Center, New York, New York, USASearch for more papers by this authorErika Romero Sandoval MD, Erika Romero Sandoval MD Hospital Nacional Cayetano Heredia, Lima, PeruSearch for more papers by this authorMark Izzard MBBS, FRACS, Mark Izzard MBBS, FRACS Skin Institute, Auckland, New ZealandSearch for more papers by this author First published: 04 August 2019 https://doi.org/10.1111/ans.15318Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume89, Issue7-8July/August 2019Pages 982-983 RelatedInformation

BACKGROUND:The gold standard for the diagnosis of melanocytic lesions is histologic examination. However, as histologic examination can have its limitations, there are many clinical scenarios in which additional testing may be appropriate in an attempt to render a definitive diagnosis.METHODS:A literature review for three ancillary tests-comparative genomic hybridization (CGH)/single-nucleotide polymorphism (SNP) array, fluorescence in situ hybridization (FISH), and gene expression profiling by quantitative reverse transcription polymerase chain reaction (qRT-PCR)-was compiled and current use patterns were tabulated. Survey of the practice patterns of these tests by dermatopathologists was also accessed in the attendees of the American Society of Dermatopathology Annual Meeting (Chicago, 2016).RESULTS:Here we summarize the use of these molecular tests in melanocytic lesions. We found that 54.4% of the respondents surveyed utilize (or expect consultants to utilize) molecular testing of melanocytic lesions in their practice when appropriate.CONCLUSIONS:CGH/SNP arrays, FISH testing, and qRT-PCR applied to melanocytic lesions have allowed for more accurate classification. Just over half of those surveyed use molecular testing for melanocytic lesion with the majority sending their cases out for completion of the molecular test.

Perineuriomatous differentiation in solitary cutaneous melanocytic nevi has been described. We present an unusual case of a patient with multiple such perineuriomatous nevi. This presentation raises the possibility that a germline mutation may be responsible for the pathogenesis of these unusual lesions.

BACKGROUND:Appropriate use criteria (AUC) provide physicians guidance in test selection, and can affect health care delivery, reimbursement policy and physician decision-making.OBJECTIVES:The American Society of Dermatopathology, with input from the American Academy of Dermatology and the College of American Pathologists, sought to develop AUC in dermatopathology.METHODS:The RAND/UCLA appropriateness methodology, which combines evidence-based medicine, clinical experience and expert judgment, was used to develop AUC in dermatopathology.RESULTS:With the number of ratings predetermined at 3, AUC were developed for 211 clinical scenarios involving 12 ancillary studies. Consensus was reached for 188 (89%) clinical scenarios, with 93 (44%) considered "usually appropriate," 52 (25%) "rarely appropriate" and 43 (20%) "uncertain appropriateness."LIMITATIONS:The methodology requires a focus on appropriateness without comparison between tests and irrespective of cost.CONCLUSIONS:The ultimate decision of when to order specific test rests with the physician and is one where the expected benefit exceeds the negative consequences. This publication outlines the recommendations of appropriateness-AUC for 12 tests used in dermatopathology. Importantly, these recommendations may change considering new evidence. Results deemed "uncertain appropriateness" and where consensus was not reached may benefit from further research.

Spindle cell lipomas (SCL) are typically tumors of the upper back/neck (shawl region) of men (80% to 90%). In general, there is a frequent tendency to restrict the diagnosis to this specific clinical scenario and a hesitancy to diagnose SCL in women. We hypothesized that SCL in women have a more varied presentation. A total of 395 SCL were diagnosed at our institution over the last 11 years. The diagnosis of SCL in women was confirmed by re-review. Immunohistochemical stains for CD34, desmin, estrogen receptor, and p16 were performed. In a subset, fluorescence in situ hybridization to detect Retinoblastoma1 (RB1) gene deletion was performed. Of 395 SCLs, 331 (86%) occurred in men; 53 (14%) occurred in women (11 cases excluded). Of the 64 SCL in women, 58 had available material. In total, 53 of 58 were confirmed as SCL. Women were younger at diagnosis (median, 51 y; range, 5 to 76 y) compared with men (64 y; range, 23 to 98 y), P<0.0001, t test. SCL in women typically occurred outside the shawl distribution (36/53, 68%) compared with men (95/331, 29%) (P<0.001), including extremities (16/53, 30% vs. 32/331, 10%) and face (11/53, 21% vs. 47/331, 14%). Dermal SCL in women were also relatively common (16/53, 30%). The cases demonstrated varying proportions of bland spindled cells, ropey collagen, myxoid matrix, and adipocytes. By immunohistochemistry, 46/46 were CD34+, 48 of 48 were desmin negative, 33 of 42 were estrogen receptor negative, and 29 of 42 had loss of p16 expression. In total, 12 of 14 showed RB1 loss by fluorescence in situ hybridization. SCL in women frequently occurs in unconventional locations and in at a slightly younger patient age.

Follicular urate-like crystals were first described in Necrotizing Infundibular Crystalline Folliculitis (NICF), a rare cutaneous disorder with multiple waxy folliculocentric papules. Similar crystal accumulation may be seen within follicular infundibulae as an incidental finding. We describe a case showing identical crystals occurring within the horn-like crusts of a patient with erosive pustular dermatosis of the scalp (EPDS), a condition which due to its presentation can often be mistaken for nonmelanoma skin cancer. A brief overview of erosive pustular dermatosis of the scalp (EPDS) is presented in this paper.

We report a highly unusual case of a primary cutaneous squamous cell carcinoma (SCC) with intermixed enteric‐type adenocarcinomatous dedifferentiation and a small component of undifferentiated mesenchymal differentiation. We believe this is the first time this form of phenotypic plasticity has been described in cutaneous SCC.

Polymorphous sweat gland carcinoma (PSGC) is a rare adnexal neoplasm with characteristic variegated histopathologic findings and low‐grade clinical behavior. First described in 1994, only 11 cases have been reported in the literature. It is named for the multiplicity of architectural patterns that may be present: solid, tubular, trabecular, pseudopapillary and cylindromatous. Owing to the multiple architectural patterns, the differential diagnosis is broad, including metastatic adenocarcinoma and other adnexal neoplasms with ductular differentiation. We present two new cases of PSGC and review the literature on this rare tumor.

BACKGROUND:Predicting which patients will develop nodal metastasis from cutaneous squamous cell carcinoma (cSCC) remains difficult. This study evaluates a recently described histological risk model validated for mucosal head and neck SCC (HNSCC) when applied to cutaneous tumours. In this model, morphologic variables including worst pattern of invasion, lymphocytic host response and perineural invasion were shown to predict disease recurrence, loco regional recurrence and overall survival in mucosal HNSCC.METHODS:Patients with cSCC and known metastatic spread were identified from the author's database over a 5-year period between July 2007 and July 2012. Histology specimens from the original primary tumour were separately analysed by 2 histopathologists. Scores were compared against T-Stage matched control specimens without metastatic spread.RESULTS:27 patients with metastatic cSCC were identified. Scores for worst pattern of invasion (WPOI) were significantly higher in individuals with lymph node metastases (p=0.02).CONCLUSIONS:Adverse pattern of invasion, defined as presence of small tumour islands or tumour satellites may be an independent risk factor for developing nodal metastases in cSCC. These tumours are difficult to investigate histopathologically as it is difficult to be confident the correct primary is chosen for study.

We describe three cases of periocular edema with histopathologic features of intralymphatic histiocytosis without extravascular granulomas. All were elderly males with no other significant medical problems. Previous reports of periocular Melkersson–Rosenthal syndrome are identical clinically, and some reports show illustrations of intralymphatic histiocytosis histopathologically, in addition to other features typical of the syndrome. Given the lack of associated diseases or other features of the Melkersson–Rosenthal triad, some of these cases may be better defined as periocular intralymphatic histiocytosis.

ABSTRACTBackgroundNoncutaneous cancers of the head and neck occasionally metastasize to skin. We present a case series of patients with skin metastases from non-cutaneous malignancies of the head and neck. A literature review is presented to assess the morphology, pattern of distribution, and morbidity of skin metastases.MethodsRelevant cases were identified by a dermatopathologist and cases were reviewed. A literature search yielded 94 cases which were also included.ResultsThe most common primary site, histology, and location of spread was the thyroid gland (42%), squamous cell carcinoma (42%), and scalp (25%) respectively. Skin metastases typically present as a discrete nodules, but the distribution varies. Metastases to skin can occasionally be a patients presenting complaint, but irrespective of timing of presentation portend a poor prognosis.ConclusionSkin metastases are clinically rare, and when present typically herald a poor overall prognosis. Information regarding their distribution and clinical presentation is of importance to the surgeon and oncologist.How to cite this articleEmanuel H, Emanuel P. Cutaneous Metastasis of Head and Neck Malignancy. Int J Head Neck Surg 2015;6(2):57-63.

Acute corneal hydrops (hydrops corneae) is an incompletely understood complication of keratoconus and other corneal ectatic disorders, including keratoglobus and pellucid marginal corneal degeneration. Keratoconus is a relatively common condition; its prevalence is estimated to lie between 6.8 and 86 per 100,000 with considerable variation among international studies. With an estimated prevalence of 2.8 per cent among patients with keratoconus, corneal hydrops is considerably less common than keratoconus per se. There appears to be a gender predisposition toward males with typical age of onset around 25 years. Earlier age, poorer visual acuity and steeper keratometry at diagnosis of keratoconus, as well as severe allergic eye disease and eye rubbing, have been identified as risk factors for developing corneal hydrops. Interestingly, a history of atopy and contact lens wear do not demonstrate an increased likelihood of developing hydrops, while having a family history of keratoconus appears to have a negative correlation. Acute corneal hydrops is characterised by the development of significant corneal oedema, typically due to a spontaneous break in Desçemet’s membrane and the overlying corneal endothelium, which allows aqueous humour to migrate into the corneal stroma and epithelium. It is hypothesised that the resolution of acute corneal hydrops requires two steps. The first involves re-attachment of the detached Desçemet’s membrane to the posterior stroma, while the second involves the migration of endothelial cells to cover the gap between the edges of the two borders of the break in Desçemet’s membrane. The time taken for the first step to occur is dependent on the depth of detachment of Desçemet’s membrane and can be hastened by anterior chamber paracentesis and intra-cameral injection of non-expansile gas such as sulphur hexafluoride (SF6) speeding up the time to resolution. The second step is dependent on the size of the break in Desçemet’s membrane and the time taken for this step to occur cannot currently be shortened. The corneal oedema associated with acute corneal hydrops is self-limiting, usually resolving within six to 14 weeks in the majority of cases; however, it often leaves a visually debilitating scar in its wake. Scarring of the cornea may necessitate corneal transplantation by penetrating keratoplasty (PKP) or deep anterior lamellar keratoplasty (DALK); however, in practice, the extent of scarring dictates which procedure should be carried out. In cases where there is extensive corneal scarring, PKP is the procedure of choice due to the increased likelihood of perforation when attempting DALK.

A 10-year-old boy was diagnosed with a thick neurotropic melanoma of the lip in 2002. He is alive and well without evidence of disease recurrence 10 years later. We applied modern pathologic techniques to this lesion to highlight recent advances in melanoma diagnostics.