Author: Dr Anthony Yung, Dermatologist, Waikato District Health Board, Hamilton, New Zealand, 2007. Updated by A/Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand; Dr Anthony Yung, 2016.
Pathology is the study of diseases. It includes the study of the causes, course and progression and the complications that arise from the disease.
Anatomic pathology, or histopathology, refers to the study of the structural and compositional changes that occur in organs and tissues as a result of disease.
A pathologist is a doctor trained in anatomic pathology that examines, describes and interprets pathological specimens to arrive at a specific finding or diagnosis.
Dermatopathology is the study and description of structural and compositional changes that occur in skin disease.
From a practical point of view, dermatopathology involves the microscopic examination, description and interpretation of biopsy specimens obtained from the skin. This is usually carried out by a general pathologist (who may or may not have had specific training in dermatopathology) or by a dermatopathologist (a doctor trained specifically in dermatopathology, but who may not have fully trained in anatomic pathology). Dermatopathologists often have training in clinical dermatology.
The interpretation of skin specimens can be complicated and difficult, as many diverse inflammatory skin diseases share the same basic inflammatory process or pattern. The final diagnosis requires clinical input and clinicopathological correlation.
How are skin biopsy specimens examined?
Skin biopsy specimens are processed and then stained with Haematoxylin and Eosin (H&E). Eosin is acidic in nature and stains basic / alkaline / acidophilic structures red/pink. Haematoxylin is alkaline, and stains acidic / basophilic structures (eg, deoxynucleic acid, ribonucleic acid within cell nuclei) blue. Depending on the observed dermatopathological pattern present and/or the clinical features, special stains may be requested to identify agents causing the condition (e.g. bacteria or fungi), specific substances deposited in the skin (e.g. amyloid, iron or melanin) or specific markers to identify the origin, nature and distribution of cells in the specimen being examined.
The specimen is systematically examined by looking at the structure of the epidermis, dermis, subcutis, fascia and underlying structures. Based on the findings, the pathologist may come up with a definitive diagnosis, or list several possible explanations, creating a differential diagnosis. The integration of clinical information in conjunction with the pathological findings generates the final diagnosis, or list several possible explanations, creating a differential diagnosis. The integration of clinical information in conjunction with the pathological findings generates the final diagnosis.
Potential errors in diagnosis
Pathologists depend on the clinician supplying a good history and differential diagnosis, and their job is easier with a large biopsy sample than with a small one. Even then, the sample may not be representative of the disease as a whole.
The biopsy may have been taken from the wrong lesion.
The biopsy may not contain diagnostic material.
The biopsy may be fragmented or crushed.
There may be processing errors.
Incorrect diagnosis may arise because of lack information on the request form.
The microscopy may appear normal despite quite obvious clinical disease.
Changes may be too subtle to diagnose if the lesion is very early in its development.
Secondary changes obscure primary pathology. These include excoriation, ulceration, healing, infection, necrosis and fibrosis.
The thin section examined by the pathologist may not contain any part of the lesion present in another portion of the original specimen. In this case, a smaller biopsy sample might have led to the diagnosis.
Dense cellularinfiltration may obscure the presence of another pathological feature, preventing its identification.
Two quite different skin diseases might appear similar under the microscope.
Abundant melanin in basal layer or throughout epidermis
Sharp demarcation of base of epidermalhyperplasia
Largely located above the surrounding epidermis
Irritated seborrhoeickeratoses may show many features suggestive of malignancy, and can be difficult at times to differentiate from squamous carcinoma.
Cohesive nests of basaloid tumour cells (sometimes with a small amount of squamous differentiation)
Peripheral palisading of nuclei at the margins of cell nests
Retraction artefact (clefts) around cell nests
Variable inflammatory infiltrate and ulceration.
Pathology of basal cell carcinoma
Pathology of basal cell carcinoma
Actinic keratosis
The histological features of actinic keratosis are:
Hyperkeratosis and/or ulceration
Columns of parakeratosis, overlying atypical keratinocytes, separated by areas of orthokeratosis
Basal atypical keratinocytes with varying degrees of overlying loss of maturation, hyperchromatism, pleomorphism, increased and abnormal mitoses, dyskeratosis – full thickness change may be called ‘Bowenoid actinic keratosis’
Variable superficial perivascular or lichenoid chronic inflammatory infiltrate