Histopathologic diagnosis of pigmented lesions of the skin

The present review deals with the histopathologic diagnosis of the commonest pigmented lesions of the skin with emphasis on melanocytic tumors. The discussed entities are systematized in pigmented lesions with and without an increase in the number of melanocytes, i.e. melanocytic hyperplasia, and in those that actually are melanocytic neoplasias. Histopathological, ultrastructural, and immunohistochemical features of relevance for the differential diagnosis are discussed in depth. One section is dedicated to the immunohistochemical markers of melanocytic lesions, the other one to the electron microscopy of malignant melanoma. Neoplasms simulating malignant melanoma and the less frequent variants of this tumor are also discussed. The diagnosis of pigmented lesions of the skin represents one of the most frequent and difficult challenges in dermatopathology, and useful clues for the differential diagnosis, especially of melanocytic dysplasias and neoplasias, are presented in the present article.     

A comparison of machine learning methods for the diagnosis of pigmented skin lesions

We analyze the discriminatory power of k-nearest neighbors, logistic regression, artificial neural networks (ANNs), decision tress, and support vector machines (SVMs) on the task of classifying pigmented skin lesions as common nevi, dysplastic nevi, or melanoma. Three different classification tasks were used as benchmarks: the dichotomous problem of distinguishing common nevi from dysplastic nevi and melanoma, the dichotomous problem of distinguishing melanoma from common and dysplastic nevi, and the trichotomous problem of correctly distinguishing all three classes. Using ROC analysis to measure the discriminatory power of the methods shows that excellent results for specific classification problems in the domain of pigmented skin lesions can be achieved with machine-learning methods. On both dichotomous and trichotomous tasks, logistic regression, ANNs, and SVMs performed on about the same level, with k-nearest neighbors and decision trees performing worse.     

Erdheim-Chester disease of the brain: cytological features and differential diagnosis of a challenging case

Erdheim-Chester disease (ECD) is an uncommon, systemic xanthogranulomatous disorder, with distinct clinicopathological features, that is rarely expected preoperatively. We describe a case that presented in the brain of a 26-yr-old male patient and clinically mimicked the appearance of a neoplasm. The final diagnosis was a surprise. In retrospect, the diagnosis was suggested by the intraoperative "squash" preparations, which demonstrated a mixed cellular proliferation of lymphohistiocytic elements and large, multinucleated cells with vesicular nuclei, prominent nucleoli, and abundant cytoplasm. To the best of our knowledge, this is the first report detailing the cytopathological features of ECD.     

Inter-observer variation in the histopathological diagnosis of clinically suspicious pigmented skin lesions

When a biopsy is taken of a suspicious pigmented skin lesion, histological examination is expected to establish the definitive diagnosis. This study evaluated the inter-observer variation of 20 pathologists in the histological diagnosis of a randomly selected set of suspicious pigmented skin lesions (PSLs), by comparing their diagnoses to a reference diagnosis. Overall sensitivity for melanoma was 87%, ranging from 55% to 100% between the observers. Sensitivity was significantly lower for thin (Breslow thickness <1 mm) than for thick melanomas (83% versus 97%, p=0.005). Overall melanoma specificity was 94%, ranging from 83% to 100% between observers. Dysplastic naevus was the most important source of false-positive diagnoses, mainly in situ melanomas. Positive and negative predictive values in the given test set were 75% and 97%, respectively. In the case of melanoma, there was quite some variation in measured Breslow thickness. This would have led to a different therapeutic approach in 12% of the readings. Some of the variation seemed to be due to a different interpretation of the presence of a co-existent naevus. In 9% (3/35) of the readings, participants did not agree on the presence of ulceration. These results reflect a tendency to overdiagnose mainly thin melanomas in general histopathological practice. They also demonstrate variation in the assessment of major prognostic factors of melanoma.     

Serum inflammatory markers in the diagnosis and assessment of Crohn’s disease activity

IntroductionThe aim of our study was to evaluate the diagnostic characteristics of selected inflammatory markers and the results of multiplication of their concentrations in the diagnosis and assessment of Crohn’s disease (CD) activity.MethodsWe studied 49 patients with CD and 31 healthy controls. The CD patients were assigned to subgroups with active and inactive disease based on the Crohn’s Disease Activity Index score. Serum interleukins and C-reactive protein (CRP) were measured using immunoassays.ResultsSerum CRP and interleukins: IL-6, IL-17A, IL-23 were significantly higher in the CD group than in controls, with the best diagnostic performance for IL-23. Only serum IL-6 and CRP were significantly higher in active than in inactive disease, with the better performance of CRP. Multiplication results did not perform better than individual multipliers.ConclusionsSerum CRP may be useful in the assessment of CD activity and there is a need for introduction of IL-23 for the CD diagnosis.     

Atypical fibroxanthoma: differential diagnosis from other sarcomatoid skin lesions

Atypical fibroxanthoma (AFX) is an uncommon cutaneous neoplasm that usually presents as a rapidly-growing nodule in sun-exposed sites in elderly patients. Despite its highly atypical histological appearance it is almost always associated with innocuous clinical behaviour. AFX is now generally regarded as the superficial counterpart of undifferentiated pleomorphic sarcoma (so-called malignant fibrous histiocytoma [MFH]). The former lesion is associated with an excellent prognosis in view of its small size, superficial location, and amenability to complete excision. Because a distinction between AFX and MFH requires assessment of the depth of invasion, a definitive diagnosis of AFX cannot be made on the basis of shallow biopsies. Other cutaneous tumours, including sarcomatoid squamous cell carcinoma (SCC) and spindle-cell melanoma, may have a histologic appearance that is indistinguishable from AFX on haematoxylin–eosin stained slides; immunochemical stains are therefore mandatory in the pathologic evaluation of such cases. There are no currently-known specific immunohistochemical markers (including CD10) which are diagnostic of AFX, and it remains a diagnosis of exclusion. Recent studies have highlighted the importance of other markers, such as high molecular-weight keratins (e.g., CK5/6, 34BE12, and MNF116) and p63 in the diagnosis of sarcomatoid squamous cell carcinoma; that tumour may fail to label for other keratin proteins. Recently, uncommon variants of AFX have been described that broaden its histological differential diagnosis.     

Castleman’s disease of the left parotid gland: a case report

Castleman’s disease is a very rare heterogeneous group of lymphoproliferative disorders characterized by non-neoplastic growths. It is unknown about the pathophysiology of the Castleman’s disease. Previous studies demonstrated that Castleman’s disease can be divided into two groups according to clinical classification, including unicentric Castleman disease (UCD) and multicentric Castleman disease (MCD). The hyaline vascular type is most common in the head and neck, and is abbreviated as UCD. In the present case, a woman complained that a mass in her parotid gland was growing and it was painless seven months ago. The computed tomography (CT) showed that the superficial lobe of the parotid gland on the left had an elliptical soft tissue density shadow, about 2.5×3.5 cm, with clear boundaries and no obvious abnormalities in the surrounding bone. The CT scan showed no obvious abnormalities in the shape and density of the right parotid and bilateral submandibular glands. After the operation, combined with the results of immunohistochemistry, the final diagnosis was Castleman tumor. The patient recovered smoothly, after the operation and during follow-up. The patient maintained good health without recurrence or metastasis.     

Automated segmentation of pigmented skin lesions in multispectral imaging

The aim of this study was to develop an algorithm for the automatic segmentation of multispectral images of pigmented skin lesions. The study involved 1700 patients with 1856 cutaneous pigmented lesions, which were analysed in vivo by a novel spectrophotometric system, before excision. The system is able to acquire a set of 15 different multispectral images at equally spaced wavelengths between 483 and 951 nm. An original segmentation algorithm was developed and applied to the whole set of lesions and was able to automatically contour them all. The obtained lesion boundaries were shown to two expert clinicians, who, independently, rejected 54 of them. The 97.1% contour accuracy indicates that the developed algorithm could be a helpful and effective instrument for the automatic segmentation of skin pigmented lesions.     

Fractal characterisation of boundary irregularity in skin pigmented lesions

A growing literature shows researcher's interest in fractal analysis, arising from its ability to describe and characterise quantitatively the complexity of several tumour profiles. The aim of the work was to investigate the fractal properties of skin pigmented lesion boundaries. Although melanoma is one of the most aggressive tumours, early detection and a high rate of diagnostic accuracy, followed by timely excision, can allow complete recovery in melanoma patients. A modified approach to fractal dimension estimation was performed that was able to consider, in a data fit procedure, the range in which lesions show fractal properties. Identification of this zone is the most important step towards a correct fractal analysis procedure. The method was checked against a known fractal dimension object (Koch's curve) with an error of 0.007. The fractal dimension was estimated in 110 skin pigmented lesions and showed a significantly increasing linear regression (p<0.05), from common naevi to naevi with dysplasia to melanomas. This result is important for screening, as it can inform the decision to excise precociously malignant lesions or to avoid unnecessary removal of benign ones. The limitations of the method are discussed.     

Genetic correlation between thyroid hormones and Parkinson’s disease

Parkinson’s disease (PD) was reported to be connected with thyroid diseases clinically, which might be a critical clew to immune pathogenesis of PD. However, there was no further research to study the pathogenesis correlation between PD and thyroid diseases. In this study, except for investigating the difference in thyroid hormone between PD and the control group, we explored genetic correlation between thyroid and PD. We tried to find their shared molecular pathway by analyzing the effect of PD risk genes on thyroid function. Interestingly, most of those 12 meaningful SNPs we found could affect PD and thyroid function through immune mechanism, which is consistent with our original conjecture and provides significant evidence for the immune pathogenesis of PD.     

Heavily pigmented renal cell carcinoma: a case report, with review of the literature and differential diagnosis

Clear cell carcinoma is the most common histotype among renal cell tumors. The prominent vascular network of sinusoidal vessels lined by delicate endothelial cells may often lead to hemorrhagic areas with secondary deposition of chunky birefringent hemosiderin granules. The finding of pigmentation other than iron, and in particular melanin deposits, in renal tumors is a rare occurrence that should lead to differential diagnosis with other primary and metastatic tumors of the kidney.     

Prehistological evaluation of benign and malignant pigmented skin lesions with optical computed tomography

Discrimination of benign and malignant melanocytic lesions is a major issue in clinical dermatology. Assessment of the thickness of melanoma is critical for prognosis and treatment selection. We aimed to evaluate a novel optical computed tomography (optical-CT) system as a tool for three-dimensional (3-D) imaging of melanocytic lesions and its ability to discriminate benign from malignant melanocytic lesions while simultaneously determining the thickness of invasive melanoma. Seventeen melanocytic lesions, one hemangioma, and normal skin were assessed immediately after their excision by optical-CT and subsequently underwent histopathological examination. Tomographic reconstructions were performed with a back-propagation algorithm calculating a 3-D map of the total attenuation coefficient (AC). There was a statistically significant difference between melanomas, dysplastic nevi, and non-dysplastic nevi, as indicated by Kruskal-Wallis test. Median AC values were higher for melanomas compared with dysplastic and non-dysplastic nevi. No statistically significant difference was observed when thickness values obtained by optical-CT were compared with histological thickness using a Wilcoxon sighed rank test. Our results suggest that optical-CT can be important for the immediate prehistological evaluation of biopsies, assisting the physician for a rapid assessment of malignancy and of the thickness of a melanocytic lesion.     

Expression of vitamin D receptor decreases during progression of pigmented skin lesions

1,25-dihydroxyvitamin D3 affects proliferation, differentiation, and apoptosis and protects DNA against oxidative damage with a net tumorostatic and anticarcinogenic effect. It acts through a specific nuclear receptor that is widely distributed through the body. Although a beneficial role of vitamin D in melanoma patients has been suggested, there is lack of information on the changes in the expression pattern of vitamin D receptor during progression of pigmented lesions. Using immunohistochemistry, we analyzed the expression of vitamin D receptor in 140 samples obtained form 82 patients, including 25 benign nevi, 70 primary cutaneous melanomas, 35 metastases, 5 re-excisions, and 5 normal skin biopsies. The strongest expression was observed in normal skin that significantly decreased in melanocytic proliferations with the following order of expression: normal skin > melanocytic nevi > melanomas = metastases. The vitamin D receptor expression in skin surrounding nevi and melanoma was also significantly reduced as compared to normal skin. Tumor-infiltrating and lymph node lymphocytes retained high levels of vitamin D receptor. There was negative correlation between tumor progression and vitamin D receptor expression with a remarkable decrease of the immunoreactivity in nuclei of melanoma cells at vertical versus radial growth phases and with metastatic melanomas showing the lowest cytoplasmic receptor staining. Furthermore, lack of the receptor expression in primary melanomas and metastases was related to shorter overall patients' survival. In addition, the receptor expression decreased in melanized melanoma cells in comparison to amelanotic or poorly pigmented cells. Therefore, we propose that reduction or absence of vitamin D receptor is linked to progression of melanocytic lesions, that its lack affects survival of melanoma patients, and that melanogenesis can attenuate receptor expression. In conclusion, changes in vitamin D receptor expression pattern can serve as important variables for diagnosis, predicting clinical outcome of the disease, and/or as a guidance for novel therapy of melanomas based on use of vitamin D or its derivatives.     

Aspects of the differential diagnosis of clear-cell lesions of the skin in connection with the rare case of a clear-cell atypical fibroxanthoma

Clear-cell changes are rare in histological specimens of the dermis and raise complex diagnostic considerations regarding lineage differentiation (e.g., epithelial, mesenchymal, or melanoctyic). We present a clear-cell atypical fibroxanthoma (CCAFX) and describe the morphological and immunohistochemical aspects of this rare skin lesion. Furthermore, we give an overview of the differential diagnoses of clear-cell lesions of the skin for a practical approach.     

Extensive pigmented villonodular synovitis with markedly pigmented lymphadenopathy and its implication for differential diagnosis with malignant melanoma

A 51-year-old male presented with a 5 cm left knee mass. Fine needle aspiration revealed large epithelioid cells with prominent nucleoli and abundant cytoplasmic pigment, consistent with malignant melanoma. Left inguinal lymphadenopathy was present, which was suspicious for metastatic disease by ultrasound examination. A dark perianal skin lesion was also identified, therefore raising the possibility of a primary melanoma. The knee and perianal lesions were resected and inguinal sentinel node biopsy was performed. In the specimen from the knee, there were clusters and fascicles of spindle and epithelioid cells with prominent nucleoli. Many of the cells displayed abundant, granular, brown, cytoplasmic pigment. The lymph node showed clusters of similar cells located in the subcapsular sinus. Immunohistochemical study showed that the cells expressed CD68, but failed to express S-100, MART-1, and gp100. The cytoplasmic pigment was positive for iron staining. The final diagnosis was pigmented villonodular synovitis. This case illustrates that pigmented villonodular synovitis may present with lymphadenopathy, mimicking a malignant process, including melanoma. Immunohistochemical studies may be essential for establishing the correct diagnosis.