Dermatopathology: Classification of Cutaneous Lesions

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The book reviews in detail the sensitivity and specificity of commonly available antibodies and their pattern of immunostaining. In addition, prognostic markers are evaluated and emphasis placed on the pitfalls commonly encountered when evaluating these neoplasms. The text is complemented by a wealth of superb images. Atlas of Cutaneous Lymphomas. This atlas contains excellent clinical and histopathologic images and text of each of the types of cutaneous lymphoma around 25 entities. It is the first go-to text for those who are considering a diagnosis of cutaneous lymphoma in their differential diagnosis.

The text also includes diagnostic mimics of lymphoma and differential diagnosis tables and algorithms. The target audience is general practitioners, dermatologists, pathologists and students, residents and fellows. Atlas of Essential Dermatopathology. Skin inflammatory nontumor , Skin-melanocytic tumor , Skin tumor Nonmelanocytic.

Dermatopathology often presents considerable difficulty for the dermatologist in training when defining the subtle differences in the appearance of various conditions. This Atlas of Essential Dermatopathology is based on materials developed during dermatopathology teaching signout at the Massachusetts General Hospital and replicates the experience at the microscope.

It contains numerous hand drawn sketches and tables plus stunning histological images to describe the appearances of common dermatologic conditions. Each chapter is brief and focuses on the main learning points.

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Tables of special stains, immunohistochemical markers and a glossary of terms are also included to broaden the reader's experience. The content is based on the most frequently encountered processes in the MGH Dermatopathology Unit; it is not intended to be comprehensive but rather an outline and atlas of the essentials in diagnostic dermatopathology.

This book will therefore be an indispensable primer for trainees of all levels - students and residents alike - in dermatology and pathology. Of all the techniques used to treat non melanoma skin cancer, the highest cure rates belong to the Mohs surgical procedure. Critical to this technique is optimal preparation and interpretation of frozen sections. The second edition of this highly successful atlas details both common and uncommon cutaneous neoplasms that can serve as a source of reference for established practitioners and a review for those in training.

It includes new frozen section specimens, the most current diagnostic guidelines, and discussion of the advancements in tissue staining. Covering pertinent clinical and histopathologic encountered in private and academic dermatopathology practice, it enables you to gain a comprehensive understanding of this critical subspecialty area.

Biopsy Interpretation of the Skin: Primary Non-Lymphoid Cutaneous Neoplasia. Primary Non-Lymphoid Cutaneous Neoplasia, Second Edition, is a concise, practical resource with a strong focus on diagnosis. It offers guidelines on how and when to biopsy the skin and provides superb coverage of common and uncommon non-lymphoid neoplasms of the skin. Clinical Features, Pathogenesis, Treatment. This book is a comprehensive compendium of current knowledge on inherited and autoimmune blistering diseases that relates advances in our understanding of the pathogenetic mechanisms to management of the individual diseases.

The book opens by describing the structure and biology of the epidermis and basement membrane zone and discussing the genes and proteins that are targets for mutations and autoantibodies. The role of the various diagnostic tests is explained, and clinical manifestations of the specific diseases are presented with the aid of many high-quality illustrations. The forms of treatment appropriate in specific conditions are then described in depth, with coverage of dressings, drugs, surgical procedures, gene therapy, and other novel approaches.

Helpful algorithms are included both for testing and monitoring and for treatment. Clinical Atlas of Skin Tumors. This superb atlas presents an unrivaled wealth of original high-quality clinical photographs of almost all benign and malignant skin tumors. The diverse sub-types and clinical forms, including different localizations, are depicted and careful attention is paid to evolution and follow-up.

While the main focus is on the clinical presentation as reflected in the photographs, diagnostic clues and management considerations are also summarized in a straightforward, readily understandable way. Participants provided their independent diagnosis and treatment suggestion for each specimen. Our study received institutional board review approval from the University of Washington. Shave, punch, and excisional biopsies were included, while consultative cases and re-excisions were excluded. The final test cases included melanocytic neoplasms. Permuted block randomization whereby cases are assigned to blocks of equal size for all possible permutations followed by random block selection allocated the cases into five test sets, each comprising 48 cases.

One of the five test sets was randomly chosen for use in the present study. Detailed information regarding test set development is provided elsewhere. Participants then sequentially evaluated test cases one hematoxylin and eosin-stained glass slide per case using a multi-headed microscope with a digital projector, driven by one of the authors SK. The order of case presentation was randomly assigned before viewing. Participants were informed that these treatment options should be regarded as suggestions for consideration, as they were developed using U.

Participants were instructed to assume that the biopsy was representative of the entire lesion and that the lesion was present at the margin.

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Patient age, biopsy type, and anatomic site were also provided. Data were independently transcribed into an electronic database by two authors JL and GZ , and ambiguities in data entry due to handwriting were resolved by joint consensus review to ensure data fidelity. Case-level diagnoses and treatment suggestions constituted the primary outcomes.

Second, write-in diagnoses for which a differential diagnosis was provided by participants e. This was only performed when diagnoses provided in the histologic differential corresponded to different MPATH-Dx classes. Illegible write-in diagnoses were treated as missing data. Choice of mutually exclusive treatment options e.

Of potential write-in responses 16 pathologists each interpreting 48 cases , A total of test case interpretations had completely mapped MPATH-Dx diagnoses with treatment responses and were analyzed. While some cases were uniformly interpreted with the same diagnostic term e. For example, Figure 1 shows a slide image with diagnoses ranging from benign e.

Figure 2 shows a similar spectrum of diagnostic terms applied to another case. The photomicrograph depicts a broad lesion with irregular epidermal thinning and thickening. Note cases are ordered by increasing treatment severity and do not reflect the actual order of case presentation to participants. Write-in diagnoses exclude missing data from one pathologist. Widely varying terminology was used by pathologists for its histopathologic interpretation and diagnosis.

The photomicrograph depicts a broad lesion comprised mainly of nevoid melanocytes in the dermis. The distribution of diagnoses and treatment considerations are shown in Table 1 and Figure 3. Mean unweighted and weighted kappa coefficients for MPATH-Dx classes assuming the least severe write-in diagnoses were 0. A comparable magnitude of inter-rater agreement was observed when assuming the most severe write-in diagnosis, with mean unweighted and weighted kappa coefficients of 0. Mean unweighted inter-rater kappa coefficient for agreement regarding treatment was 0. Increasing severity of diagnoses after mapping into MPATH-Dx classes was associated with increasing intensity of suggested treatment considerations Table 1.

Correlation between MPATH-Dx diagnostic classification assuming the least severe write-in diagnosis, when necessary and treatment was 0. Similarly, correlation between MPATH-Dx classes, assuming the most severe write-in diagnosis when necessary, and treatment was 0.

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Achieving diagnostic agreement for melanocytic skin lesions remains challenging. In the absence of substantial technological advances enabling precise classification of these neoplasms, complete elimination of disagreement is overly ambitious. We believe that the litany of diagnostic terms is and will remain a substantive contributor to diagnostic discordance for melanocytic lesions. To our knowledge, this is the largest study describing the variability in diagnostic terms applied to melanocytic neoplasms.

Our results highlight the diverse diagnostic terminology used by pathologists and illustrate concise mapping of these terms into the MPATH-Dx hierarchy. Find articles by Arun C Inamadar.

Author information Article notes Copyright and License information Disclaimer. Received Sep; Accepted Oct. This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3. This article has been cited by other articles in PMC. Abstract Use of immunohistochemical technique is increasing in diagnosing various diseases. Immunohistochemistry , dermatopathology , immunostaining.

Introduction Use of immunohistochemical technique is increasing in diagnosing various diseases. Basic Principles of Immunohistochemical Analysis IHC is the method of localization of antigens in tissue sections using labeled antibodies, visualized by markers chromogen. Procedure Immunohistochemical analysis is usually performed on formalin-fixed, paraffin-embedded tissue sections, which are mounted on specially coated or charged glass slides for better adherence. Normal Antigen Expression in Skin and Some Other Tissues Human skin is an important area of antigen expression, many of which may contribute to various skin disorders.

Table 1 Common antigen distribution in different components of normal skin[ 5 , 6 ]. Open in a separate window. Practical application of IHC in dermatology Table 2 lists the common antigens, which are helpful in diagnosing skin lesions by immunohistochemical analysis. Application of IHC in diagnosing skin tumors. Melanoma Immunohistochemical analysis is of value in the diagnosis of various clinical subtypes of primary cutaneous melanoma and metastatic melanoma from unknown primary. This is a relatively specific and most useful marker for melanoma cells. It is a helpful marker in frozen sections for delineating surgical margins for residual or recurrent melanoma during Mohs surgery.

Currently it is considered as one of the most important melanoma markers, producing strong and diffuse expression. It may also be present in some benign melanocytic lesions. Desmoplastic melanoma is the only type, consistently negative for this marker. An antibody detecting a kDa glycoprotein expressed by normal and neoplastic melanocytes.

Ki67 detectable by MIB1antibody: It is a proliferation marker for melanoma cells. Microphthalmia transcription factor MiTF: This is a melanocytic nuclear protein crucial for growth, development and viability of melanocytes in embryonic and postnatal life. It also plays a role in synthesis of melanin. It is not a specific marker and the specificity is much lower in spindle cell variant of melanoma. However, its specificity is less as it stains melanocytic nevi equally strongly and hence its utility is limited.

It is not effective to detect desmoplastic melanoma. Vimentin, epithelial membrane antigen, cytokeratin, muscle-specific actin, neuron-specific enolase; cytokeratins may be positive in some metastatic melanoma.

Distinction between melanoma and melanocytic nevi The clinical and histopathological features of melanoma may often be overlapping with melanocytic nevi. CD99 expression is focally positive for some cases of spitz nevi whereas spitzoid melanoma shows predominantly diffuse staining pattern. Nucleolin protein is a major nucleolar argyrophilic protein involved in carcinogenesis.

Heat shock protein HSP There is overexpression in melanoma cells, especially in metastatic melanoma. Glucose transporters Glut-1, Glut Glut-1 is expressed in benign melanocytic nevi, which is downregulated in majority of the melanoma cells. Prognostic markers for melanoma Ki67 is associated with vertical growth phase of the tumor and hence is a prognostic marker. Nucleolin protein is the second powerful prognostic indicator after melanoma thickness. MAP-2 expression is a predictor of disease progression and significantly correlates with Breslow vertical tumor thickness, Clark level and stage of disease.

Fatty acid-binding protein 7 FABP7 expression may be associated with tumor progression and invasion; it is associated with Ki67 score. Expression of HSP on melanoma cells is associated with widespread metastasis and poor prognosis. Phospho-histone H3 pHH3 rapidly assesses the mitotic activity of malignant cells and is considered as a mitotic marker.

Dysregulation of cell adhesion molecules is associated with progression of melanoma. Carcinoembryonic antigen cell adhesion molecule-1 CEACAM-1 may have a role in progression of melanoma and serves as a potential prognostic marker in melanoma. RUNX3 is an important tumor suppressor playing role in cell proliferation, apoptosis and tumor metastasis.

Positive RUNX3 expression in human melanoma is an important prognostic factor in patient outcome. Benign and malignant fibrous and fibrohistiocytic tumors of skin The different tumors in this group are as follows: Table 3 Distinguishing features of different benign and malignant fibrous tumors of the skin[ 24 ]. Adnexal and epidermal tumors Though most of these tumors present with classical clinical and histopathological pictures, overlapping features may pose diagnostic difficulty at times.

Cutaneous metastasis of unknown origin Metastatic cutaneous nodules may be the first indicator of an internal malignancy. Table 4 Some immunohistochemical markers for unknown cutaneous metastasis[ 7 ]. Alopecia areata Immunological alteration play major role in the pathogenesis of alopecia areata. Scarring alopecia In scarring alopecia, there is inflammation involving the permanent portion of the hair follicle, resulting in irreversible hair loss. Folliculotropic cutaneous T-cell lymphoma In this malignant disorder of the hair follicle, patient presents with non-specific features; clinical pictures simulating follicular mucinosis or dissecting cellulitis have been reported.

There is consistent expression of bcl CD5 and CD43 expression are not seen. Primary cutaneous diffuse large B-cell lymphoma, leg type PCLBCL ; this is a tumor common in elderly females with unfavorable prognosis and tendency to disseminate. The cells are positive for CD20 and CD79a and there is strong expression of bcl Expression of bcl-6 is seen in most cases and CD10 is usually negative. Primary cutaneous diffuse large B-cell lymphoma, other; variant, intravascular large B-cell lymphoma; these are usually cutaneous manifestations of systemic lymphoma, sometimes presenting with only skin lesions.

The prognosis is good except in the intravascular variant. Application of IHC in diagnosing other disorders. Becker's nevus There is an increased expression of androgen receptors in dermal fibroblasts of Becker's nevus, compared to normal skin, in both males and females. Leprosy Increased expression of Langerhans cell and dermal dendrocyte markers like CD1a and factor XIIIa in skin lesions of tuberculoid leprosy indicates a role of dendritic cells in eliciting host response toward Mycobacterium leprae.

Lymphatic metastasis M2A antigen D monoclonal antibody is expressed in lymphatic endothelial cells; it is a marker to identify intralymphatic malignant cells and sentinel lymph node positivity. Vascular tumors GLUT1 antigen is expressed in all types of congenital hemangiomas, pyogenic granuloma and granulation tissues. Schamberg's disease Immunohistochemical analysis of skin specimens from patients with Schamberg's disease reveals that there is expression of adhesion receptors leukocyte function adhesion 1 [LFA-1],[ 38 ] endothelial leukocyte adhesion molecule 1 [ELAM-1],[ 38 ] intercellular adhesion molecule 1 [ICAM-1] [ 38 ] on the endothelial cells in the early stage of the disease, highlighting its pathogenesis.

In detection of microorganisms Immunohistochemical methods to detect antigens of various microorganisms are now available.

Viral; Cytomegalovirus, herpes simplex, human papilloma virus, hepatitis B virus, Epstein-Barr virus. Allergic contact dermatitis Serotonin is involved in the pathogenesis of allergic contact dermatitis ACD and immunohistochemical detection of serotonin receptors 5-HT1AR and 5-HT2AR in the early lesions may help in targeted therapy by blocking these receptors.

Advantages of IHC Good sensitivity and specificity. The technique is performed on paraffin-embedded tissue sections, which allows preservation of cellular details in a better way compared to frozen sections. It can be used upon specimens stored for a long duration and previously stained tissue sections. IHC has an edge over routine enzymatic tissue staining by its ability to identify wider arrays of tissue antigens.

Immunohistochemical preparations can be utilized for electron microscopy immuno-electron microscopy. Immunohistochemical methods have equivalent sensitivity as direct immunofluorescence technique and it has replaced many uses of electron microscopy. Disadvantages of IHC False positive and false negative results. Non-specific staining as well as aberrant immunoreactivity are the technical snags associated with IHC. Hence, diagnosis by IHC should always be supplemented by some confirmatory method.

The chromogen DAB imparts a brown color to the tissue section creating confusion with melanin pigment.

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