Noncutaneous Sites Research Articles

Non-cutaneous syncytial myoepitheliomas are identical to cutaneous counterparts: a clinicopathologic study of 24 tumors occurring at diverse locations.

Cutaneous syncytial myoepithelioma (CSM) is a rare myoepithelioma variant of skin, characterized by intradermal syncytial growth of spindle cells with a distinct immunophenotype of EMA and S100 positivity and infrequent keratin expression. While CSM was first described as a cutaneous tumor, singular non-cutaneous cases have since been reported in bone. We aimed to investigate the clinicopathological features of this variant across all anatomic sites through a large multi-institutional study. We complied a total of 24 myoepitheliomas with syncytial growth from our files. The tumors occurred in 12 male and 12 female patients (M:F = 1:1), with a median age of 31 years (range, 9-69 years). While the majority of tumors (75%, n = 18) occurred in skin, a significant subset (25%, n = 6) arose in non-cutaneous sites, including bone (n = 3), bronchus/trachea (n = 2), and interosseous membrane of tibia/fibula (n = 1). Tumor size ranged from 0.4 to 5.9 cm. Clinical follow-up (7 patients; range 14-202 months; median 56.5 months) showed a single local recurrence 8 years after incomplete skin excision but no metastases; all patients were alive at the time of last follow-up without evidence of disease. Histologically, all tumors were pink at low-power and characterized by a syncytial growth of bland ovoid, spindled, or histiocytoid cells with eosinophilic cytoplasm and prominent perivascular lymphoplasmacytic inflammation. One-third displayed adipocytic metaplasia (8/24). Rare cytologic atypia was seen but was not associated with increased mitotic activity. All tumors expressed S100, SMA, and/or EMA. Keratin expression was absent in most cases. Molecular analysis was performed in 16 cases, all showing EWSR1-rearrangments. In total, 15/15 (100%) harbored an EWSR1::PBX3 fusion, whereas 1 case EWSR1 FISH was the only molecular study performed. Syncytial myoepithelioma is a rare but recognizable morphologic variant of myoepithelioma which may have a predilection for skin but also occurs in diverse non-cutaneous sites. Our series provides evidence supporting a reappraisal of the term "cutaneous syncytial myoepithelioma," as 25% of patients in our series presented with non-cutaneous tumors; thus, we propose the term "syncytial myoepithelioma" to aid pathologist recognition and avoidance of potentially confusing terminology when referring to non-cutaneous examples. The behavior of syncytial myoepithelioma, whether it arises in cutaneous or non-cutaneous sites, is indolent and perhaps benign with a small capacity for local recurrence.

Association between halo nevi and melanoma in adults: A multicenter retrospective case series

To the Editor: The halo nevus is thought to be of little concern in children. In adults, however, a new-onset halo nevus has been suggested to be a harbinger of melanoma either within the halo nevus or at distant cutaneous or noncutaneous sites, according to case reports and small case series.1Epstein W.L. Sagebeil R. Spitler L. Wybran J. Reed W.B. Blois M.S. Halo nevi and melanoma.JAMA. 1973; 225: 373-377Crossref PubMed Scopus (62) Google Scholar,2Pellegrini J.R. Wagner Jr., R.F. Nathanson L. Halo nevi and melanoma.Am Fam Physician. 1984; 30: 157-159PubMed Google Scholar Multiple widely used dermatologic reference texts3Bolognia J. Schaffer J.V. Cerroni L. Dermatology: 2-Volume Set. Elsevier, Philadelphia, PA2017Google Scholar,4James W.D. Berger T.G. Elston D.M. Andrews' Diseases of the Skin. Saunders/Elsevier, London, England2011Google Scholar and online references (eg, UpToDate.com, DermNetNZ.org) advocate extensive melanoma screening in adults with new-onset halo nevus, including full cutaneous, oral, ophthalmic, and vaginal examinations, despite limited evidence supporting an association between halo nevus and melanoma. We aimed to further investigate the association between new-onset halo nevus and melanoma in adults by evaluating the incidence of melanoma in the year after a new halo nevus diagnosis. A multicenter retrospective chart review of clinical and histopathologic records at 8 university hospitals identified 879 patients in whom 888 halo nevi were diagnosed at aged 18 years or older (Brigham and Women's Hospital [n = 80], Massachusetts General Hospital [n = 166], New York University [n = 7], Northwestern University [n = 36], Oregon Health & Science University [n = 103], University of Pennsylvania [n = 27], Huntsman Cancer Institute and the University of Utah [n = 364], and Yale University [n = 96]). Ethical approval was obtained from each university's institutional review board. Patients being treated with immunotherapy for melanoma were excluded. Mean age at halo nevus diagnosis was 36.3 years (standard deviation 13.2 years) (Table I). Clinical records review identified 95 occurrences of melanoma in these 879 patients. Only 9 halo nevi were diagnosed within 1 year before melanoma diagnosis, representing a melanoma incidence rate of 0.01 (95% confidence interval 0.004-0.017) per person per year. All 9 of these melanomas represented primary cutaneous melanoma; there were no occurrences of primary noncutaneous melanoma, metastatic melanoma, or melanoma within the incident halo nevus. None of these 9 patients presented with multiple halo nevi. The remaining 86 melanoma diagnoses occurred either before the halo nevus diagnosis (n = 78) or greater than 1 year after (n = 8) (mean 5.75 years [standard deviation 4.30 years]). Personal history of vitiligo was not significantly associated with odds of melanoma development within the year after an incident halo nevus (odds ratio 3.97; 95% confidence interval 0.65-24.2; P = .13).Table IPatient demographicsCharacteristicAll patients with HN, n = 879Patients with melanoma diagnosed in the year after a new HN, n = 9Patients without melanoma diagnoses, n = 784Mean age at HN diagnosis ± SD, y36.3 ± 13.239.1 ± 11.935.3 ± 12.7 18–39580 (66)5 (55.6)540 (68.9) 40–59212 (24.1)4 (44.4)174 (22.2) 60–7968 (7.7)051 (6.5) ≥801 (0.1)01 (0.1) Unknown18 (2.0)018 (2.3)Mean age at melanoma diagnosis ± SD, y39.4 ± 14.740.4 ± 11.8NASex Men348 (39.6)5 (55.6)307 (39.3) Women529 (60.2)4 (44.4)475 (60.6) Unknown2 (0.2)02 (0.3)Race White799 (90.9)9 (100)711 (90.7) Nonwhite18 (2.0)017 (2.2) Unknown62 (7.1)056 (7.2)Halo nevus biopsied Yes396 (45.1)6 (66.7)345 (44.0) No474 (53.9)3 (33.3)431 (55.0) Unknown9 (1.0)08 (1.0)Vitiligo Yes78 (8.9)2 (22.2)70 (8.9) No450 (51.2)3 (33.3)391 (49.9) Unknown351 (39.9)4 (44.4)323 (41.2)Values are provided as No. (%) unless otherwise indicated.HN, Halo nevus; NA, not applicable; SD, standard deviation. Open table in a new tab Values are provided as No. (%) unless otherwise indicated. HN, Halo nevus; NA, not applicable; SD, standard deviation. Limitations of the study include the retrospective design and heterogeneity by which each site identified halo nevus cases. Halo nevus and melanoma were identified by documentation and coding that may not accurately reflect the true date of onset or incidence. In conclusion, this study found that adult-onset halo nevi were associated with a 1% risk of primary cutaneous melanoma development in the year after halo nevus diagnosis, with no cases of primary noncutaneous or metastatic melanoma. This melanoma risk is comparable to that of individuals with a history of atypical nevi or personal or family history of melanoma.5Varedi A. Bishop M.D. Boucher K.M. Kim C.C. Grossman D. Powering a prospective melanoma chemoprevention trial in high-risk cohorts.Int J Dermatol. 2019; 58: e232-e234Crossref PubMed Scopus (3) Google Scholar Given these findings, we recommend annual total body skin examinations in adults with a new diagnosis of halo nevus and without additional risk factors, and we do not advocate reflexive screening for primary noncutaneous or metastatic melanoma.

Itching, chloroquine, and malaria: a review of recent molecular and neuroscience advances and their contribution to mechanistic understanding and therapeutics of chronic non-histaminergic pruritus.

Chloroquine (CQ) is an antimalarial drug that elicits severe pruritus in black Africans with malaria fever. This acute itching (2-7days duration) exhibits age dependency and a racial and genetic predilection. CQ itch is non-histaminergic, which makes it both a good model and a tool to probe the mechanisms of chronic itch. This review focuses on recently discovered mechanisms, neuroscience, mediators, and receptors that are implicated in molecular studies of CQ pruritus. CQ pruritus mechanisms are also compared to that of itching following other systemic diseases, such as chronic kidney disease, chronic liver disease, skin disorders, and burns. There are striking similarities between CQ itching pathways and other chronic itch secondary to systemic disease with or without skin lesions, which have not been previously highlighted. Prominent among these are the shared roles of skin, neural and spinal μ opiate receptors, kappa opiate receptor, nitric oxide, serotonin via 5HT1B/D receptors, cytokines, especially interleukins, and tumor necrosis factor. There is elaborate "cross talk" among the diverse mediators and receptors involved in CQ-induced pruritus. CQ also binds to the mas-related G protein coupled receptors MrgprA3/MrgprX1 present in a small proportion (4-5%) of dorsal root ganglion neurons and skin. The mrgprA3 CQ receptors are coupled to PLC-β3 and a chloride channel to initiate skin itch action potentials in C nerve fibers. Mrgpra3/X1 couples to TRPA1 for calcium influx into neuronal cells at noncutaneous sites. Central CQ itch occurs via gastrin-related peptide (GRP) and its receptor (GRPR) in the dorsal spinothalamic tracts, as well as glutamic mediated GRP projection to parabrachial nucleus. The possibility of chronic itch therapy based on personalized medicine, genetics, and transcriptomics or the use of itch "polypill/polycream" are discussed.

Indoor Tanning and the Risk of Developing Non-Cutaneous Cancers: A Systematic Review and Meta-Analysis

Despite a strong association between indoor tanning and the risk of cutaneous cancers, the relationship between indoor tanning and non-cutaneous cancers is unknown. Our objective was to estimate the association of indoor tanning with developing non-cutaneous cancers. We conducted a systematic literature review and meta-analysis of the association between indoor tanning and non-cutaneous cancer sites. Associations were estimated using random effects models. Heterogeneity was investigated through subgroup analyses and the Q-test and I2 statistics. From 15 identified studies, 33 effect estimates for 12 cancer sites were included in the review. Adjustment for sun exposure was a significant source of heterogeneity in the association of indoor tanning and non-cutaneous cancer risk (meta-regression p = 0.0043). When restricting to studies that adjusted for solar ultraviolet radiation (7 studies and 19 effect estimates) a potential increased risk was observed among ever users of indoor tanning devices with the risk of hematologic malignancies (pooled relative risk = 1.11; 95% CI 0.96–1.28), with differing effects observed by hematologic types and subtypes of non-Hodgkin lymphoma. No association was observed among solid non-cutaneous cancers (pooled relative risk = 0.98; 95% CI 0.94–1.19). Neither study design nor geographical region was significant sources of heterogeneity in these associations. When controlling for sun exposure, indoor tanning does not protect against solid non-cutaneous cancers and may increase the risk of some hematologic malignancies. Given the well-established relationship with skin cancer and potential relationship with hematologic malignancies, efforts to reduce the use of indoor tanning devices should continue.

Primary cutaneous marginal zone lymphomas with plasmacytic differentiation show frequent IgG4 expression

The expression of IgG4 in malignant B-cell lymphomas has only partially been studied. Recent reports described single cases of marginal zone lymphomas arising in the ocular adnexae that express IgG4. Moreover, a subset of dura-associated marginal zone lymphomas appear to express IgG4 as well. We investigated IgG4 expression in a more systematic manner in a large cohort of marginal zone lymphoma specimens derived from the archive of our institute. Overall, we examined 169 marginal zone lymphomas of various primary sites that displayed a distinct plasmacytic differentiation and light chain restriction, allowing for a detailed investigation of the immunoglobulin heavy chain expression in these tumors by immunohistochemistry. Unexpectedly, primary cutaneous marginal zone lymphomas showed frequent IgG4 expression. Although only 1 out of 120 noncutaneous marginal zone lymphomas, located in the ocular adnexae, expressed IgG4, 19 of 49 (39%) primary cutaneous marginal zone lymphomas showed this feature, constituting the highest expression rate of IgG4 reported to date in any B-cell lymphoma. None of the IgG4-positive cutaneous marginal zone lymphomas with available clinical data showed evidence of a preexisting systemic IgG4-related disease, suggesting a localized immunologic IgG4-driven pathogenetic process at early stages of the disease. IgG4-positive and IgG4-negative primary cutaneous marginal zone lymphomas did not significantly differ in architectural features of the infiltrate or the composition of the reactive T-cell infiltrate as determined by analysis of T-cell content, CD4/CD8 ratio, and content of FOXP3- and PD1-positive T cells. Although the pathogenetic role of IgG4 expression in a significant subset of primary cutaneous marginal zone lymphomas with plasmacytic differentiation remains unclear at present, the demonstration of IgG4 expression in a marginal zone lymphoma involving the skin might be a helpful clue in the routine diagnostic setting, as these tumors will almost invariably be of primary cutaneous origin with an extremely low risk of spread to noncutaneous sites and an excellent prognosis.

Histopathological atlas and proposed classification for melanocytic lesions in Tyr::NRasQ61K; Cdkn2a−/− transgenic mice

Reference EPFL-ARTICLE-188431doi:10.1111/pcmr.12115View record in Web of Science Record created on 2013-09-09, modified on 2017-05-12

Melanoma of ocular, mucosal, and genital sites: Epidemiology and survival outcomes.

9051 Background: Melanomas arising from noncutaneous sites are rare entities with poorly defined staging, prognosis and no evidence-based treatment guidelines. Methods: We analyzed melanoma cases in the Surveillance, Epidemiology and End Results database between 1988 and 2007. Differences in clinical and pathologic features, treatment, and mortality were studied according to primary site of disease. The risk of melanoma-related death was calculated from life tables based on expected survival. Relative survival was compared in a multivariable parametric model using individual data. Results: We identified 209,861 cases of melanoma, of which 9,267 (4.4%) were noncutaneous. These were notable for older age, higher proportion of women, racial minorities, and advanced-stage disease. Mortality was high, even in subgroups with localized stage at diagnosis. Mucosal melanomas of the gastrointestinal and genitourinary tract had the highest excess mortality hazard ratios (HR) in the multivariate model. A substantial proportion of patients underwent organ-specific radical resection (32% eye enucleation, 40% radical head/neck surgery, 31% gastrectomy, 23% abdominoperineal resection). Conclusions: Melanoma arising from mucosal sites portends markedly worse prognosis than cutaneous melanoma. Prospective studies of systemic adjuvant treatment are needed for this disease, which is rarely curable even with aggressive local therapy. [Table: see text]

Early Screening in Patients With Head and Neck Cancer Identified High Levels of Pain and Distress

Pain and distress are recognized as the fifth and sixth vital signs in cancer care, respectively, as debilitating symptoms that are frequently under-recognized. The aim of this study was to document, using touch-screen technology, levels of pain and distress in patients with head and neck cancer before their assessment at a head and neck multidisciplinary referral clinic. A cross-sectional study over a 4-year period (2008 through 2011) was conducted for patients attending a head and neck oncology multidisciplinary team clinic in the Hunter New England referral district of Australia. Predictor variables were cancer stage and site. Cancer sites divided into 8 different regions, with distinction made for cutaneous versus noncutaneous sites. Outcome variables consisted of pain and distress levels. Pain was assessed using a Numerical Rating Scale of 0 to 10, and distress was assessed using the Distress Thermometer and PSYCH-6 scales. In the context of a screening study and for statistically comparing pain with other variables, pain was regarded as any score higher than 0. Clinically significant distress represented a Distress Thermometer score higher than 3 and a PSYCH-6 score of at least 3. Data analysis consisted of descriptive statistics, variance contrasts, and 2-tailed Pearson correlations. Four hundred thirty-six patients were included in the study, with an equal number of cutaneous and noncutaneous cancer sites. Thirty-four percent of patients reported having pain, and 13% had clinically significant distress. Tumor stage did not significantly affect pain or distress scores. There is a high level of pain and distress reported by patients with head and neck cancer before their assessment and management is discussed.

Parotid Gland Metastasis from a Rectal Carcinoma

Sir, Metastasis to the parotid gland usually results from cutaneous malignancies of the head and neck (70 %)—melanomas and squamous cell carcinomas and an additional 15 % from non-cutaneous sites of the head and neck [1]. When a primary cancer originates below the clavicle, metastasis to the parotid gland is uncommon (15 %). The common sites of metastasis from colorectal adenocarcinomas are the liver, lung and the regional lymph nodes. Parotid localization from a rectal carcinoma is an extremely rare finding. Herein, we report a case with primary rectal carcinoma with metachronous parotid metastasis and also discuss the treatment implications relevant to metastases to the parotid gland. A 40-year-old man with no known co-morbid illness underwent an abdominoperineal resection for an adenocarcinoma lower rectum following neoadjuvant chemoradiation (50Grey external beam radiotherapy +2 cycles of 5 Fluorouracil). The post operative histopathology was suggestive of a residual mucinous adenocarcinoma, with metastasis in 4 out of the 11 perirectal nodes (Stage III- ypT3N2a). He received 6 cycles of adjuvant 5-FU plus oxaliplatin (FOLFOX) chemotherapy and was on regular follow up. Two years later he presented with an insidious onset 4x3cm parotid swelling, a fine needle aspiration cytology suggested a diagnosis of adenocarcinoma. A PET-CT scan revealed only an isolated uptake in the right parotid region (Fig. 1ab). Fig. 1 a Whole body PET scan revealed only an isolated uptake in the right parotid. b PET-CT scan revealed only an isolated uptake in the right parotid region He subsequently underwent a right total parotidectomy, a portion of the angle of mandible and the buccal branch of the facial nerve was sacrificed for adequate clearance (Fig. 2a–c). The right level II cervical lymph node was negative for malignancy on frozen section and hence a formal neck dissection was not considered. Histopathological examination showed a 3.5 × 3 cm tumor in the right parotid with features suggestive of mucinous adenocarcinoma with metastasis in 2 intra parotid lymph nodes which was morphologically similar to the primary rectal adenocarcinoma. Immunohistochemical studies showed tumor cells positive for CEA and CK-20, confirming the final diagnosis of parotid metastasis from rectal adenocarcinoma (Fig. 3a–e). He further went on to receive 5 cycles of Capecitabine plus oxaliplatin (XELOX) chemotherapy. However, within a month of completion of the second line chemotherapy he developed disseminated metastasis and opted to be on best supportive care. Fig. 2 a Preoperative clinical photograph. b Intra-operative photograph of a right total parotidectomy, a portion of the angle of mandible and the buccal branch was sacrificed for adequate clearance. c Specimen right total parotidectomy photograph Fig. 3 a H&E X 10- Metastatic adenocarcinoma right parotid. b H &E X 20—Parotid tumor. Cells are seen in clusters, acini and as signet ring cells. c Parotid Lymph Node X 20—Metastatic Carcinoma CEA positivity. d Parotid Lymph ... Metastases to the parotid gland are generally quite rare—in a series including more than 6,000 patients of benign and malignant parotid tumors, the incidence of parotid metastasis was around 8.1 % [1] Parotid gland metastasis is usually an ominous sign and more so, if the primary tumor is located below the clavicles. The common infra clavicular primaries include breast, prostate, kidney and the gastrointestinal tract. To the best of our knowledge, only a very few primary colorectal cancer patients with parotid metastases have been reported in the literature [2–4]. Metastatic lesions in the parotid gland can occur at intraglandular, paraglandular or parenchymatous levels and are frequently difficult to distinguish from primary tumors of the gland. Many studies have clearly shown that surgical resections of hepatic or lung metastases for colorectal malignancy patients provide survival benefits; however, the role of surgery for a solitary parotid metastasis has not yet been defined because of the rarity of the condition. Extrapolating the data from hepatic and pulmonary metastasectomy patients, it seems to be reasonable to perform parotid surgery for those patients with isolated parotid metastases. However the issues pertaining to the extent of the surgery (total versus superficial parotidectomy), the need for a prophylactic lymph node dissection and the need for radiotherapy continue to remain controversial [5]. The presence of gross residual disease both in the primary and in 4 of the 11 perirectal nodes following neoadjuvant chemo radiation and the presence of metastasis in the intra parotid lymph nodes may have contributed to the poor prognosis in our patient despite the use of oxaliplatin based chemotherapy. In conclusion, a margin negative excision coupled with consolidation chemotherapy seems to be the best available therapeutic option to conclusively diagnose and manage a parotid gland metastasis from a rectal cancer.

Balloon cell melanoma of the anal canal: A wolf in sheep′s clothing?

Balloon cell melanoma (BCM) is a rare histologic variant of cutaneous malignant melanoma with exceptional reports of occurrences at non-cutaneous sites. Herein we present a case of primary amelanotic BCM of anal canal, a heretofore undescribed location. Histologically, the tumor was characterized by sheets of pale cells that bore striking resemblance to foamy macrophages. Presence of rare atypical mitoses confirmed the malignant nature of the cells. Neoplastic cells were immunoreactive for S100, Melan-A, and focally for HMB-45 while were negative for myogenic, gastrointestinal stromal tumor, epithelial and neuroendocrine markers. Resemblance to foamy macrophages, bland cytology and absence of pigment imparts this tumor a deceptively benign histological appearance making it prone to diagnostic pitfalls. Awareness of this rare entity and judicious employment of immunohistochemistry is imperative in segregating it from its diverse mimics.

Cutaneous Metastasis of Transitional Cell Carcinoma in 12 Dogs

In humans, cutaneous metastasis of transitional cell carcinoma (TCC) has been attributed to direct extension, lymphatic or hematogenous dissemination, or surgical implantation. The purpose of this study was to characterize the clinical and histologic features of cutaneous TCC metastasis, confirmed by uroplakin-III immunohistochemistry, in dogs. The 12 cases were 9 spayed female and 3 neutered male dogs, 6 to 14 years old (mean, 11 years). Four dogs had a history of urinary incontinence. Three had undergone abdominal surgery for TCC diagnosis or treatment. The primary neoplasms were 7 papillary infiltrating and 5 nonpapillary infiltrating TCC. Cutaneous lesions were detected at a mean of 123 days (median, 38 days) after diagnosis of the primary TCC and appeared as plaques, papules, or nodules in, with 1 exception, perineal, inguinal, or ventral abdominal dermis or subcutis. Of 8 dogs with dermal TCC, 5 had epidermal erosion or ulceration. In 10 dogs, TCC was detected in cutaneous lymphatic vessels, identified by endothelial immunoreactivity for Prox1. Metastases were also detected in lymph nodes in all dogs and at distant noncutaneous sites, usually the lungs, in 10 dogs. Mean survival after diagnosis was 162 days (median, 90 days). Despite medical treatment of 10 dogs after the development of cutaneous metastasis, remission was not achieved; 4 dogs had stable disease. Although TCC could have spread to skin by direct extension or lymphatic or vascular dissemination, the proximity of most cutaneous metastases to the vulva or prepuce raises the additional possibility of transepidermal spread through urine-scalded skin.

Extranodal diffuse large B cell lymphoma of cutaneous follicle centre lymphoma type: a study of 24 patients with non‐cutaneous primary limited stage extranodal diffuse large B cell lymphoma in support of a new concept

Follicle centre cell lymphoma of small cell type showing either a follicular or diffuse growth pattern similar to cutaneous follicle centre lymphoma (cFCL) has been recognized in extranodal non-cutaneous sites. Our aim was (i) to investigate whether diffuse large B cell lymphoma (DLBCL) of cFCL type could be identified in extranodal non-cutaneous sites and (ii) whether clinical characteristics similar to primary cFCL could be recognized. Of 24 extranodal non-cutaneous DLBCLs, nine (38%) had large centrocytoid morphology and 15 (62%) were either 'centrocytoid and centroblastic' or 'centroblastic and immunoblastic'. Six centrocytoid cases were Irf-4 negative, Bcl-6 positive and at most weakly CD10- or Bcl-2-positive by immunohistochemistry, consistent with DLBCL of cFCL type. All patients with cFCL type were stage IE and were significantly younger than other patients. Recurrences occurred in two patients and were exclusively extranodal. Our results suggest that DLBCL of cFCL type can be identified in extranodal non-cutaneous sites and shows clinical characteristics similar to genuine cFCL. We propose to expand the concept of cFCL to encompass large cell lymphomas in extranodal sites.

Detection of human papillomavirus DNA in feline premalignant and invasive squamous cell carcinoma

Squamous cell carcinoma (SCC) is the most common malignant cutaneous and oral neoplasm of cats. Papillomavirus (PV) DNA has been identified in a proportion of feline Bowenoid in situ carcinomas (BISCs), cutaneous SCCs and a single oral SCC, but its exact role in the pathogenesis remains unknown. In humans, it has been suggested that ultraviolet (UV) light and human PV (HPV) may act as cofactors in cutaneous SCC carcinogenesis. Little is known about the influence of UV light on PV prevalence in feline cutaneous lesions, including actinic keratosis (AK). Additionally, PV prevalence in noncutaneous feline lesions, including oral SCC, is largely not known. This study aimed to determine the presence of PV in 84 cats with premalignant and invasive SCC from cutaneous and noncutaneous sites using polymerase chain reaction and to investigate an association with UV light. Papillomaviral DNA was amplified from two of 12 cases of AK, seven of 22 BISCs, nine of 39 cutaneous SCCs and two of 35 non-cutaneous SCCs. Of the PV DNA sequenced, 50% was most similar to HPV of the genus Betapapillomavirus, while the other 50% was most similar to Felis domesticus PV type 2. Exposure to UV was not associated with an increase in PV for cutaneous SCC. The results of this study suggest that in the cat, HPV DNA may be detectible within a higher percentage of squamous lesions than previously demonstrated, UV exposure may not be a confounder for PV presence, and noncutaneous lesions may have a low prevalence of PV.

Diagnostic utility of EWS break-apart fluorescence in situ hybridization in distinguishing between non-cutaneous melanoma and clear cell sarcoma

Clear cell sarcoma (CCS) is a rare soft tissue sarcoma with morphological similarities to malignant melanoma (MM), but with a distinct genetic background that includes the chromosomal translocation t(12;22)(q13;q12). Clear cell sarcoma is often misdiagnosed as MM because of similarities in target locations and immunophenotypes. Eighteen cases with MM in non-cutaneous sites were subjected to fluorescence in situ hybridization (FISH) to assess EWS gene breakage. Tissue microarrays were constructed using formalin-fixed, paraffin-embedded tissue and the EWSR1 (22q12) dual-color, break-apart rearrangement probe (Vysis) was used. Two patients were classified as CCS with EWS gene rearrangement, with a mean of 67.5% positive cells per sample according to break-apart FISH. The remaining 16 patients lacked break-apart signals of the EWS gene. The presence of type 1 (EWS exon 8-ATF1 exon 4) fusion transcripts was confirmed in FISH-positive patients by RT-PCR. Retrospective analysis revealed that the masses were located in the foot and buttock, respectively. Morphologically, tumor cells were not typical for those of CCS or MM. Break-apart FISH is an accurate and convenient method for differentiating between MM and CCS. Molecular detection of EWS gene rearrangement, either by break-apart FISH or RT-PCR, is mandatory in subjects with melanotic tumors of soft tissue.

Lipoid proteinosis of the larynx in siblings: exploring new modalities of treatment

Lipoid proteinosis is a rare autosomal recessive disease inheritance with deposition of hyaline-like material at cutaneous and non-cutaneous sites. This is a report of two siblings presenting with typical cutaneous and laryngeal manifestations of lipoid proteinosis since birth who were treated successfully with placental extract.

Control of Pseudomonas aeruginosa Skin Infections in Mice Is Mast Cell-Dependent

Mast cells (MCs) have recently been shown to be essential for the elicitation of efficient immune responses in murine sepsis. To explore whether MCs also contribute to the control of bacterial skin infections, we studied skin lesions induced by Pseudomonas aeruginosa (PA) in genetically MC-deficient Kit(W)/Kit(W-v) mice, normal Kit(+/+) mice, and MC-reconstituted Kit(W)/Kit(W-v) mice. PA injections resulted in strikingly (>2-fold) larger skin lesions in Kit(W)/Kit(W-v) mice than in Kit(+/+) mice, which exhibited pronounced MC degranulation at infection sites. In addition, neutrophil recruitment following PA injections and bacterial clearance from sites of infection was significantly impaired in Kit(W)/Kit(W-v) mice compared with Kit(+/+) mice. Notably, the adoptive transfer of MCs to the skin of Kit(W)/Kit(W-v) mice before PA infection resulted in normal neutrophil accumulation as well as skin lesions comparable with those in Kit(+/+) mice in both bacterial burden and size. These findings demonstrate for the first time that activated MCs are crucial for the induction of protective innate immune responses to bacterial skin infections.

F-18-fluoro-deoxy-glucose positron emission tomography in the assessment of peripheral T-cell lymphomas

F-18-fluoro-deoxy-glucose positron emission tomography (PET) is highly sensitive and specific in the imaging of B-cell lymphomas. In contrast, its utility in the diagnostic evaluation of T-cell lymphomas is less defined. In this article, we present our finding utilizing PET in peripheral T-cell lymphomas (PTCL). A retrospective review of patients who underwent PET examinations at our institution produced 24 PET examinations among patients with PTCL. A lesion-based analysis was undertaken to evaluate the diagnostic accuracy of PET in PTCL. PET findings were compared with a standard of reference and sensitivity, specificity, positive and negative predictive values were calculated. PET had an overall sensitivity of 86% and specificity of 100%. PET had high sensitivity (95%) at nodal and non-cutaneous extra-nodal sites and poor sensitivity (13%) at cutaneous sites. The mean SUV of abnormal foci in anaplastic large cell lymphoma was 11 mg/ml (range: 3 – 40), and PTCL-unclassified was 8 mg/ml (range: 1 – 23).

Textbook of melanoma, John F. Thompson, Donald L. Morton, Bin B. Kroon (Eds.). Martin Dunitz, an imprint of Taylor and Francis, London (2004), 400 pages. $395.00. ISBN: 1-90-186565-7.

The saying, “You cannot judge a book by its cover” rings true very often. However, with regards to the Textbook of Melanoma, the cover represents its contents well. (The two most striking features found on the cover of the Textbook of Melanoma are its appropriate title and the eye-catching bright orange cover.) Webster's dictionary defines textbook as “a book that contains the principles of a subject, or a literary work relevant to the study of a subject.” This book contains the principles of all things melanoma and presents them clearly and concisely. Edited by three physicians from three different continents and containing input from more than 90 contributors, the Textbook of Melanoma presents 14 sections and 64 chapters in a concise and easy to read manner. The book begins with an intriguing and informative history of melanoma. Portraits of John Hunter, who is credited with the first published account of melanoma in 1787, and Rene Laennec, who is debatably the first to describe melanoma as a disease entity in 1804, immediately give life to the book. The final chapter presents practical and useful guidelines for such topics as primary prevention, secondary prevention, treatment of primary and recurrent melanoma, and follow-up suggestions, along with levels of evidence to support these guidelines. Sandwiched between chapters 1 and 64 are 62 comprehensive and informative chapters that cover many topics relating to melanoma, including the role of sunscreens, prevention strategies, surface microscopy, the management of lymph nodes, and melanoma in children. For completeness sake, there is also an entire section devoted to primary melanoma in noncutaneous sites, including primary melanoma of the gastrointestinal tract and ocular melanomas. This is a “textbook” in the true meaning of the word. Another theme of the book is the color orange. Not only is it the color of the cover, it is encountered throughout the book as the background for multiple concise and informative charts, tables, graphs, and illustrations. The bright orange color becomes a welcome sight as it presents large amounts of information superbly summarized within its confines. In this case, one can tell a book by its cover. Orange and aptly named, the Textbook of Melanoma will be a welcome site on many bookshelves for years to come.

Primary Mucinous Carcinoma of the Scalp-A Case Report

Primary mucinous carcinoma of the skin is a rare tumor with only cases reported in the literature since the first description of a case by Lennox et al. in 1952. This tumor is a histologic subtype of sweat gland carcinoma. Because of the histopathologic appearance, primary mucinous carcinoma of skin can be mistaken for metastasis from extracutaneous sites. Most cases occur mainly between the fifth and the seventh decade of life. They are growing slowly with a propensity for local recurrence and metastasis. This tumor has not been widely reported in the plastic surgery literature. We describe a 59-year-old woman with a tumor on the right scalp. This lesion enlarged progressively and showed a reddish, elevated, dome-shaped surface. Excisional biopsy of the tumor revealed mucinous carcinoma. Further treatment involved wide local excision and reconstruction. In attempt to improve the recognition of this clinical entity, we discuss the histopathology, clinical course, surgical management and prognosis. Mucinous carcinoma can occur in noncutaneous visceral sites and metastasize to the skin. Systemic investigation were undertaken to exclude the possibility of metastatic mucinous carcinoma.

Textbook of Melanoma

This major new text is a well-presented and comprehensive review of melanoma. This first edition is presented in hardback with over 650 pages of text divided into 14 sections, which are further subdivided into 64 chapters. It has 94 contributors who practice in 14 different countries and therefore represents a truly global overview of current practice. Despite its size, the book is easy for the reader to navigate through due to its simple layout and well-structured chapters. It also benefits from over 300 colour illustrations, photographs, and line drawings, and many helpful tables and information boxes. The index is extensive making specific information easy to find and all chapters are well referenced. The ‘Textbook of Melanoma’ includes sections on the basic biology of the pigment cell system, the aetiology, prevention, and screening of melanoma, and histopathology, classification, staging, and prognosis. It also covers diagnostic methods, the management of primary cutaneous melanoma, regional lymph nodes, and locally recurrent melanoma, as well as the diagnosis and systemic therapy of metastatic disease. There is also a useful chapter on primary melanoma in noncutaneous sites, and a review of current published guidelines. All chapters include a historical perspective, detailed information regarding current understanding and best practice and where appropriate, challenges to the legitimacy of current practice with possible alternatives. For example, the chapter on staging systems for cutaneous melanoma describes early staging systems used from the 1950s, the application of the TMN staging system to melanoma in the 1960s, and the development of microstaging and use of Clark level and Breslow depth. The 1997 AJCC staging system for cutaneous melanoma is described in detail, and then critically analysed with proposed changes. Owing to its comprehensive nature, this text will be of interest to oncologists, dermatologists, and surgeons with an interest in skin cancer. All three editors are surgeons, and this is reflected in the detailed description of surgical procedures and operative techniques, along with colour photographs and illustrations. Any oncology text will be unable to present the latest developments in a rapidly advancing field; however, the chapter on new anticancer agents discusses new cytotoxic agents, cyclin-dependent kinase inhibitors, signal transduction inhibitors, and antiangiogenesis agents, and includes data from papers and abstracts up to and including year 2000. The ‘Textbook of Melanoma’ was clearly an ambitious project, and the editors should be congratulated on producing this important comprehensive reference book.