Pathological review of primary cutaneous malignant melanoma by a specialist skin cancer multidisciplinary team improves patient care in the UK.

AIMS: The National Institute for Health and Care Excellence advocated the development of specialist skin cancer multidisciplinary teams (SSMDTs) for the management of higher risk invasive skin cancers in the UK. The interobserver variability in the histopathological assessment of primary cutaneous malignant melanoma (PCMM) is well recognised. METHODS: We evaluated the discordance rates in the assessment of the histopathological criteria of PCMM based on the eighth American Joint Committee on Cancer (AJCC) melanoma staging system and subsequent change in prognosis and management following pathology review by an SSMDT. RESULTS: 353 cases of PCMM were referred to our SSMDT between April 2015 and May 2016. Cases in which there was a discrepancy in one or more histological parameters following expert review were collected retrospectively. Of 341 eligible cases, there were 94 (27.6%) in which there was an alteration in any parameter. There was interobserver agreement in final diagnosis in 96.8%, Breslow thickness in 86.8%, ulceration in 98.2%, microsatellites in 98.5%, tumour mitotic rate in 88.9%, histological subtype in 92.4%, growth phase in 98.5%, angiolymphatic invasion in 97.7%, perineural invasion in 98.8%, regression in 95.3% and tumour-infiltrating lymphocytes in 95.0%. A corresponding change in AJCC stage occurred in 23 cases (6.7%), with a resulting change in clinical management in 10 cases (2.9%). CONCLUSIONS: Disagreements in the pathological assessment of PCMM can have significant clinical implications for a small number of patients. Our findings highlight the value of the SSMDT for high-quality care of patients with melanoma in the UK.

Cutaneous lupus associated with pembrolizumab therapy for advanced melanoma: a report of three cases.

Checkpoint blockade immunotherapy has revolutionized the treatment of advanced melanoma, with impressive survival benefits attained through upregulation of the anticancer immune response. Blockade of regulatory checkpoint molecules can, however, also result in aberrant immune activation leading to undesirable inflammation and autoimmunity. Although many genetic determinants have been described in patients with primary autoimmune diseases, it is uncertain whether patients developing autoimmune skin disease as an adverse effect of anti-PD-1 therapy share the same genetic risks. Furthermore, it is also unclear whether treatment with these agents can result in the unveiling of underlying 'silent' autoimmunity resulting in chronic inflammatory disease. We report three cases of cutaneous lupus associated with pembrolizumab therapy for advanced melanoma. One patient had a previous diagnosis of histologically proven discoid lupus erythematosus, well-controlled without treatment for over 2 years, which flared on first exposure to pembrolizumab. The remaining two patients had no previous history of autoimmune disease; both developed cutaneous eruptions, histologically and immunohistologically, in keeping with subacute cutaneous lupus following treatment with pembrolizumab. Our report bolsters what is currently an exceedingly small body of evidence documenting the development of cutaneous lupus in the setting of pembrolizumab therapy. Our third case specifically documents an otherwise unreported severe reflare of previously diagnosed, quiescent discoid lupus erythematosus in the setting of pembrolizumab, vividly highlighting the potential for autoimmune and specifically, lupus reactivation in the setting of anti-PD-1 therapy.

Primary Localized Cutaneous Amyloidosis Affecting Female Individuals of a Pakistani Pedigree.

Primary localized cutaneous amyloidosis is a group of rare conditions where amyloid deposition is limited to the skin without systemic manifestations. Most cases are sporadic; however, mutations in the oncostatin M receptor (OSMR) and interleukin-31 receptor A (IL31RA) genes can cause a familial form of the condition in up to 10% of cases. Here, we describe a family in which 8 female individuals are affected by either macular amyloidosis or amyloidosis cutis dyschromica. To the best of our knowledge, a sex-specific expression or the coexistence of 2 different phenotypes of primary localized cutaneous amyloidosis in 1 pedigree has not yet been reported.

Using frozen section margin control technique to manage non-melanomatous skin lesions in high-risk sites.

BACKGROUND: In the UK, non-melanoma skin cancers (NMSCs) that are incompletely excised, recurrent or in sites high risk for incomplete excision are often offered Mohs micrographic surgery (MMS). Variations in waiting times and geographical access to MMS affect patient preference for other treatments. Our unit offers excision of such lesions under complete margin frozen section histological examination. METHODS: All NMSCs excised at our unit by complete margin frozen section histological analysis from 2010 to 2014 were retrospectively reviewed. The number of excisions required, complete excision rates and recurrences to date were analysed. RESULTS: Sixty-nine patients were treated using this technique with a total of 70 lesions excised. Approximately 71% of the excision margins were clear after primary excision, 27% at second excision and 1% at third excision. Patients had a mean follow-up of 12 months (range: 1-48) with no patients lost to follow-up and no recurrences reported to date. Ninety-eight percent of NMSC cases were completely excised and two cases were incompletely excised. CONCLUSION: We have found the rates of excision and recurrence of the high-risk NMSCs excised at our unit to be comparable to those reported with MMS. In addition, our data show that around 29% of patients would have had incomplete margins on primary resection, thus justifying the use of this technique in this group. We suggest that this technique is a safe and useful alternative to MMS in areas where waiting times or geographical patient preference may prohibit its use.

Chondrosarcomatous Differentiation in a Large Malignant Melanoma of the Scalp.

Background. Divergent differentiation in malignant melanoma is a rare phenomenon, which can lead to delayed diagnosis or misdiagnosis, impacting upon patient treatment and outcome, as well as the understanding of tumour behaviour. Case. We present the case of a large long-standing tumour on the scalp of a 72-year-old female patient, which when excised and examined histologically was revealed to be a nodular malignant melanoma displaying chondrosarcomatous differentiation. Foci suggestive of lentigo maligna were also present. Rapid metastatic spread of the tumour was observed shortly after the primary resection. Discussion. To our knowledge, this is the first reported case in the literature of chondrosarcomatous differentiation in a lentigo maligna melanoma. The clinical and histopathological details and images of this case are presented alongside a discussion regarding such tumours and patterns of similar tumour behaviour.

A Left-Sided Prevalence of Lentigo Maligna: A UK Based Observational Study and Review of the Evidence.

Skin cancer has been shown to present asymmetrically, prevalent on the left side of the body, more so in subtypes of cutaneous melanoma such as lentigo maligna. Biases have been linked to cumulative UV light exposure and automobile driving patterns. Though left-right ratios have previously correlated with the side men or women tend to position themselves or countries drive on, more recent trends indicate a consistent left-sided bias. To clarify reasons for changing trends, a review of the evidence base and LM's laterality in a UK cohort (99 cases 2000-2011) was conducted for the first time. The strong correlation of left-sided excess, found in both genders (ratios 1.381-1.5, P < 0.05 X (2) 0.841), is congruent with more recent findings. Though evidence indicates that driving position is no longer a risk factor for LM, due most likely to improved car window UV protection, it remains the most commonly attributed cause. Understanding phenomena such as UV lights "scatter effect" or that cumulative exposure may not be a significant risk factor helps rationalize older conclusions that would otherwise appear contradictory. The reasons for left-sided excess remain unclear but may be due to factors requiring further research such as the body's anatomical/embryological asymmetry.

A model for lentigo maligna recurrence using melanocyte count as a predictive marker based upon logistic regression analysis of a blinded retrospective review.

BACKGROUND: The pre-malignant skin lesion lentigo maligna (LM) presents a particular challenge. Pathologists demonstrate poor diagnostic concordance and often struggle to assess whether excision margins are truly negative. This can lead to equivocal histology reports and a lack of clear guidance with which surgeons may rationalise their surgical management plans. Based upon the biological principle that tumour burden increases the chance of recurrence, we propose a shift in diagnostic paradigm, using melanocyte count (MC) at an excision margin to predict LM recurrence. METHODS: This retrospective study reviewed all cases of LM from a regional UK melanoma centre (1996-2011), to include 167 excisions, from 99 patients. Pathology slides were assessed for MC (blinded) at the most affected margin. Seven secondary markers of neoplasia were additionally evaluated. Logistic regression analysis was used to model the relationship between MC and recurrence. RESULTS: MC is a strong predictor of LM recurrence (p < 0.0001). A regression curve predicts risk for individual MCs, which may also be divided into three risk strata; low (0-11% [MC 0-20]), intermediate (15-89% [MC 21-30]), and high risk (92-100% [MC ≥ 31]). MC misclassified 0.6% of cases in the low and high risk groups compared with 21% for pathologists, who were also equivocal for 18% of excisions. MC's inter-rater concordance was high (>0.9). The secondary factors were all independently associated with recurrence, but failed to improve predictive ability supplementary to MC. CONCLUSIONS: MC confidently predicts LM recurrence and is more accurate and reliable, whilst also reducing the uncertainty of current pathology assessment. Risk estimates for any given MC can be easily charted using the regression curve graph, where confidence interval and risk group boundaries demonstrate the degree of certainty associated with any given prediction. This change in approach is congruent with tumour behaviour. A recurrence 'tipping point' corresponds to the sharp risk increase across the intermediate group's narrow band of MC.

Post radiation myofibrosarcoma of hypopharynx.

Malignant tumours of myofibroblasts are rare lesions. Post radiation sarcoma is a rare potential late sequel of ionizing radiation. We present the first case of myofibrosarcoma of the hypopharynx in a 67-year-old man, occurring 16 years after radiotherapy for laryngeal carcinoma.