Histological interpretation of spitzoid tumours: an extensive machine learning-based concordance analysis for improving decision making.

The histopathological classification of melanocytic tumours with spitzoid features remains a challenging task. We confront the complexities involved in the histological classification of these tumours by proposing machine learning (ML) algorithms that objectively categorise the most relevant features in order of importance. The data set comprises 122 tumours (39 benign, 44 atypical and 39 malignant) from four different countries. BRAF and NRAS mutation status was evaluated in 51. Analysis of variance score was performed to rank 22 clinicopathological variables. The Gaussian naive Bayes algorithm achieved in distinguishing Spitz naevus from malignant spitzoid tumours with an accuracy of 0.95 and kappa score of 0.87, utilising the 12 most important variables. For benign versus non-benign Spitz tumours, the test reached a kappa score of 0.88 using the 13 highest-scored features. Furthermore, for the atypical Spitz tumours (AST) versus Spitz melanoma comparison, the logistic regression algorithm achieved a kappa value of 0.66 and an accuracy rate of 0.85. When the three categories were compared most AST were classified as melanoma, because of the similarities on histological features between the two groups. Our results show promise in supporting the histological classification of these tumours in clinical practice, and provide valuable insight into the use of ML to improve the accuracy and objectivity of this process while minimising interobserver variability. These proposed algorithms represent a potential solution to the lack of a clear threshold for the Spitz/spitzoid tumour classification, and its high accuracy supports its usefulness as a helpful tool to improve diagnostic decision-making.

A man in his forties with rapid exacerbation of chronic foot ulcers. / En mann i 40-årene med rask forverring av kronisk fotsår.

BACKGROUND: The development of skin cancer, especially squamous cell carcinoma, is a well-known but rare and often under-recognised complication of chronic wounds and longstanding scar tissue. These skin cancers, known as Marjolin's ulcer, are more aggressive in nature than similar cutaneous cancers of different etiology, with a higher rate of local recurrence and an increased metastatic potential. CASE PRESENTATION: Our patient suffered severe trauma to his left leg and foot in a car accident during childhood and underwent extensive reconstruction. In the years leading up to today the left foot has been lymphedematous, with recurring sinuses and ulcerations. He was now admitted due to a rapidly progressing and debilitating wound. During the first consultation the clinical findings led to suspicion of malignancy and osteomyelitis. The histopathologic examination from our biopsies could not rule out the presence of a highly differentiated squamous cell carcinoma. MRI and bone biopsy revealed osteomyelitis. INTERPRETATION: With few exceptions, the treatment of malignancy in chronic wounds and longstanding scar tissue is surgical. Early diagnostics, including biopsies, and intervention are instrumental to a favourable outcome. We present this case report alongside current literature in order to raise awareness on the topic.

D2-40/p63 defined lymph vessel invasion has additional prognostic value in highly proliferating operable node negative breast cancer patients.

Phosphohistone H3 assessed proliferation has strong prognostic value. Lymph vessel invasion by D2-40 is also prognostic, but D2-40+ myoepithelial expression in small ducts completely filled by solid-pattern ductal carcinoma in situ can mimic lymphovascular invasion. As myoepithelial cells are also p63 positive, we have investigated whether lymph vessel invasion identified by combined D2-40/p63 is stronger prognostically than by D2-40 alone, and whether it has independent prognostic value to phosphohistone H3. In 240 operable T(1-2)N(0)M(0) node negative invasive breast cancer patients <71 years, phosphohistone H3 was determined by quantitative immunohistochemistry and lymph vessel invasion by D2-40/p63 double immunostaining. Correlation analysis between the clinico-pathologic factors and lymph vessel invasion, and univariate and multivariate prognostic survival analysis were performed. With median 117 (range: 12-192) months follow-up, 36 patients (15%) developed and 28 (12%) died of distant metastases. Ten of the 61 patients (16%) with cancer cells surrounded by D2-40 were p63 positive and none of these 'false lymph vessel invasion' recurred. D2-40+/p63- lymph vessel invasion occurred in 51/239 (21%) cases and correlated with grade, mitotic activity index, phosphohistone H3, ER, cytokeratin14, and HER2. D2-40+/p63- lymph vessel invasion was strongly prognostic, but far more in women ≥55 than those <55 years (P<0.0001 and 0.04). With multivariate analysis, phosphohistone H3 proliferation was the strongest single prognosticator. Lymph vessel invasion had additional prognostic value to phosphohistone H3 only in women ≥55. This group of patients, without/with lymph vessel invasion, had 10-year survival rates of 83 and 50%, respectively (hazard ratio-lymph vessel invasion=3.0, P=0.04; hazard ratio-phosphohistone H3=6.9, P=0.002). Where age was <55 years, only phosphohistone H3 had independent prognostic value. Combinations of other features had no additional value. In conclusion, T(1-2)N(0)M(0) invasive breast cancer patients ≥55 years with phosphohistone H3≥13, D2-40+/p63- defined lymph vessel invasion identifies a subgroup with a high risk of distant metastases.

Primary Leiomyosarcoma of the Pancreas-a Case Report and a Comprehensive Review.

PURPOSE: Primary mesenchymal tumors of the pancreas are rare, with leiomyosarcomas the most encountered entities among the pancreatic sarcomas. With few exceptions, single case reports published over the last six decades constitute the entire scientific literature on this topic. Thus, evidence regarding clinical decision-making is scant. METHODS: Based on a case report and an extensive literature search in PubMed, we discuss the clinical aspects and current management of this rare malignancy. RESULTS: We identified only two papers with more than a single case presentation; these institutional patient series were limited to five and nine patients. Additionally, a few papers sought to summarize the individual case reports published in the English and/or Chinese language. The clinical presentation is rather non-specific. Moreover, modern imaging modalities are insufficiently accurate to diagnose leiomyosarcoma of the pancreas. Treatment goals include a complete resection with free margins. Proper morphologic examination using immunohistochemistry and the application of a grading system are clinically important for prognostication. The efficacy of adjuvant treatments has not been established. CONCLUSION: Primary pancreatic leiomyosarcoma is extremely rare, and the scientific literature is primarily based on single case reports. Conclusions on management and prognosis should be drawn with caution. A multidisciplinary team consultation is warranted to discuss a thorough individual treatment plan based on the available scientific literature, despite its low evidence level.