Home Translating Report News Physicians Diseases Body Sites Lab tests Search
Home Diseases and Health Information


The skin is the largest organ in the body.  We don't often think of the skin as an organ, but it provides important functions besides providing us our beauty.  It is one of first immune barriers to the outside world and is an active site of the immune system processing and destroying foreign proteins and molecules.   Unfortunately, because of its large size, it is subject to the brutalizing rays of the sun and other environmental challenges, accounting for many diseases as well as skin cancers.  Pathologists who specialize in the diagnosis of skin diseases are called dermatopathologists.   They are required to have training in clinical dermatology as well as pathology in order to completely understand how skin diseases present in the patient. 

Anatomy and Histology

To understand the disease process that affect the skin, one must have a clear understanding of the anatomy and histology of the skin. Some of these terms are found in The Cell section. Other terms specific the skin may be found through these following links.

Basement membrane zone-Anchoring Complex
Dermis and Connective Tissue
Matrix Metalloproteinases
Skeletal Muscle occurring in the skin

The embryonic and fetal skin is a dynamic interface involving interactions with numerous oncogenes. Bcl-2 and bax genes are members of the bcl-2 gene family, involved in regulation of apoptosis. Bcl-2 protein is anti-apoptotic while bax is a cell death promoter. Recently, it has been shown that in the earliest development, these two proteins localize to the epidermal portion of the hair follicle. With development, bax becomes localized to areas where the hair canal is excavated and keratinization and holocrine secretion is initiated. Bcl-2 is expressed in the follicular papilla. Dendritic cells scattered throughout the basal and immediate suprabasal interfollicular epidermis and outer root sheath of the developing hair bulge express bcl-2 and HMB-45.


Laboratory/Radiologic/Other Diagnostic Testing  
Gross Appearance and Clinical Variants  
Histopathological Features and Variants  
Commonly Used Terms  
Internet Links  


Tissue Counter Analysis of Tissue Components in Skin Biopsies: Evaluation using CART (Classification and Regression Trees).

Smolle J, Gerger A.


Am J Dermatopathol. 2003 Jun;25(3):215-22. Abstract quote

In tissue counter analysis, complex histologic sections are overlaid with regularly distributed measuring masks of equal size and shape, and the digital contents of each mask (or tissue element) are evaluated by gray level, color, and texture parameters.

In this study, the feasibility of tissue counter analysis and classification and regression trees for the quantitative evaluation of skin biopsies was assessed. From 100 randomly selected skin biopsies, a learning set of tissue elements was created, differentiating between cellular elements, collagenous elements of the reticular dermis, fatty elements and other tissue components.

Classification and regression trees based on the learning set were used to automatically classify tissue elements in samples of normal skin, benign common nevi, malignant melanoma, molluscum contagiosum, seborrheic keratosis, epidermoid cysts, basal cell carcinoma, and scleroderma. The procedure yielded reproducible assessments of the relative amounts of tissue components in various diagnostic groups. Furthermore, a reliable diagnostic separation of molluscum contagiosum versus normal skin and epidermal cysts, benign common nevi versus malignant melanoma, and seborrheic keratosis versus basal cell carcinoma was possible.

Tissue counter analysis combined with classification and regression trees may be a suitable approach to the fully automated analysis of histologic sections of skin biopsies.


Three-dimensional imaging of human skin and mucosa by two-photon laser scanning microscopy.

Malone JC, Hood AF, Conley T, Nurnberger J, Baldridge LA, Clendenon JL, Dunn KW, Phillips CL.

Department of Pathology and Laboratory Medicine, Division of Dermatopathology, Department of Medicine, Division of Nephrology, Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA, and Department of Medicine, Division of Dermatology, University of Louisville School of Medicine, Louisville, KY, USA.

J Cutan Pathol 2002 Sep;29(8):453-458 Abstract quote

BACKGROUND: Various structural components of human skin biopsy specimens are difficult to visualize using conventional histologic approaches.

METHODS: We used two-photon microscopy and advanced imaging software to render three-dimensional (3D) images of in situ nerves, blood vessels, and hair follicles labeled with various fluorescent markers. Archived frozen human skin biopsy specimens were cryosectioned up to 150 micro m in thickness and fluorescently stained with rhodamine- or fluorescein-labeled antibodies or lectins. Optical sections were collected by two-photon microscopy and the resulting data sets were analyzed in three dimensions using Voxx software.

RESULTS: Reconstructed image volumes demonstrated the complex 3D morphology of nerves, blood vessels and adnexal structures in normal mucocutaneous tissue.

CONCLUSION: Two-photon microscopy and Voxx rendering software allow for detailed 3D visualization of structures within human mucocutaneous biopsy specimens, as they appear in situ, and facilitate objective interpretation of variations in their morphology. These techniques may be used to investigate disorders involving cutaneous structures that are difficult to visualize by means of traditional microscopy.



Skin pathology findings in a cohort of 1500 adult and elderly subjects.

Siragusa M, Schepis C, Palazzo R, Fabrizi G, Guarneri B, Del Gracco S, Spada RS, Ferri R.

Department of Neurology, Oasi Institute for Research and Prevention of Mental Retardation, Troina, Italy.

Int J Dermatol 1999 May;38(5):361-6 Abstract quote

BACKGROUND: No extensive studies are available in the literature on the eventual skin pathology induced by neurologic or systemic diseases in elderly individuals. Other factors, such as health and hygiene, socioeconomic status, and climate can also play an important role.

METHODS: Fifteen-hundred subjects (886 women and 614 men; mean age, 67.8 years; range, 39-90 years) were admitted to the Department of Geriatrics at the Oasi Institute between 1992 and 1997; all these subjects were carefully evaluated from a dermatologic point of view. Each subject underwent specialist examinations, routine blood analyses, thoracic X-rays, cerebral computerized tomography (CT) scan, and magnetic resonance imaging (MRI) when appropriate. A group of subjects without significant neurologic or systemic disease, comprising 116 women and 60 men (mean age, 64.5 years; range, range, 40-90 years), was selected and used as a normal control group. Subsequently, our attention was focused on the eventual presence of the following neurologic diseases: Alzheimer-type dementia, vascular dementia, mixed-type dementia, subcortical dementia, Parkinson's disease, vascular brain disease, hemiplegia, etc. Thus, different subgroups were formed on the basis of such diagnostic categories and the frequency of skin pathology in each subgroup was evaluated.

RESULTS: Of the 1500 subjects, 1439 stated that they had never been affected by dermatologic disease. No statistically significant difference in frequency of skin pathology was found between normal controls and the different patient subgroups. Unsuspected and singular dermatoses were found, however, such as paraneoplastic syndromes, idiopathic tripe palms, white fibrous papulosis of the neck as an expression of photoaging, conditions induced by former popular traditions of Sicilian culture (anetoderma secondary to the application of Hirudo medicinalis and erythema ab igne), pigmented dermatoses never described before in Italy (prurigo pigmentosa and friction amyloidosis), and nail abnormalities (atypical half-and-half nail, and dyschromic nail changes in multiple system atrophy and in hemiplegia).

CONCLUSIONS: The dermatologic screening performed in 1500 patients revealed several unexpected diagnoses and some original observations. Some rare dermatoses were described and certain hypotheses were suggested to explain the peculiar dyschromic changes of the fingernails in multiple system atrophy, the atypical cases of half-and-half nail, and the so-called idiopathic tripe palms associated with psoriasis.


The Pathology of Full-thickness Cadaver Skin Transplant for Large Abdominal Defects: A Proposed Grading System for Skin Allograft Acute Rejection.

Bejarano PA, Levi D, Nassiri M, Vincek V, Garcia M, Weppler D, Selvaggi G, Kato T, Tzakis A.

Departments of *Pathology and daggerSurgery, University of Miami School of Medicine/Jackson Memorial Hospital, Miami, FL.
Am J Surg Pathol. 2004 May;28(5):670-675. Abstract quote  

Closure of large abdominal defects after extensive abdominal surgery is a major technical surgical problem. Failure to close the abdomen leaves the patient at risk for grave complications. Full-thickness abdominal wall skin transplantation appears to solve this problem.

This is the first time that detailed histopathologic features of skin abdominal wall transplantation from cadaver donors are described. Five adults and four children underwent 10 transplants because of large abdominal wall defects. Twenty-two posttransplantation skin specimens were evaluated during a mean follow-up of 23.5 weeks, and the findings were compared with the clinical appearance of the skin. Rejection was manifested as a maculopapular rash.

The histologic features were categorized as perivascular infiltrates, epidermal changes, and stromal changes. A grading system is proposed based on the number of cases encountered: No rejection, grade 0 (n = 9): No perivascular infiltrates. Indeterminate for rejection, grade 1 (n = 2): Up to 10% of vessels show infiltrates of small lymphocytes. No eosinophils, large lymphocytes, spongiosis, epidermal, or stromal inflammation are seen. Mild rejection, grade 2 (n = 5): 11% to 50% of vessels are infiltrated by small lymphocytes. Eosinophils and mild spongiosis may or may not be present. No epidermal infiltrates, stromal infiltrates, or large lymphocytes are seen. Moderate rejection, grade 3 (n = 4): Greater than 50% of vessels show lymphocytic infiltrates that may be accompanied by epidermal and stromal inflammation. Spongiosis is absent or mild. Endothelial plumping, eosinophils, and large lymphocytes may be seen. Severe rejection, grade 4 (n = 2): Greater than 50% of vessels show infiltrates, but different from moderate rejection, there is dyskeratosis and the epidermis shows heavier lymphocytic infiltrates and moderate to severe spongiosis. The stroma shows infiltrates extending into the base of the epidermis. Endothelial plumping, eosinophils, and large lymphocytes are present.

The mean number of weeks after transplantation for the development of clearcut rejection (grades 2-4) was 8.36. Among the 9 nonrejection cases, 4 specimens from 3 patients had thrombosis of the vessels feeding the graft. A grading system serves to better assess skin allograft rejection.

Am J Dermatopathol 2001;23:1-7.
Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

Commonly Used Terms
Gross Clinical Description Characterization
Blister Vesicle or bulla
Bulla Fluid-filled area greater than 5 mm across
Dimples Invagination of the skin
Crust Deposit of inspissated material which may contain plasma (red cells, white cells, or both)
Exanthem Skin eruption occurring as a symptom of a general disease, usually an infectious process
Excoriation Traumatically induced lesion leading to breakage of the epidermis
Lichenification Thickened skin formed by repeated rubbing
Linear Following a line, may follow Lines of Blaschko
Macule Flat and circumscribed area of any size
Nodule Elevated solid area greater than 5 mm across
Onycholysis Loss of integrity of the nail substance
Papule Elevated solid area 5 mm or less
Photosensitivity Lesions are distributed in areas exposed to ultraviolet radiation
Plaque Elevated flat topped lesion, usually greater than 5 mm across
Pruritis Itching
Punch Biopsy A type of biopsy where an instrument punches out a small cylinder of skin, usually ranging from 2 to 6 millimeters 
Pustule Pus filled raised area
Scale-Crust Combination of scale and crust
Shave Biopsy A type of biopsy where a superficial shave of the skin is performed
Sporotrichoid Spread Lymphangitic spread with nodules that ascend proximally along lymphatic vessels
Wheal Transient raised erythematous area which blanches


Clinical Signs Characterization
Deck Chair Sign

Sparing of the creases in skin folds in an erythroderma consisting of confluent flat-topped pink papules and associated with a peripheral eosinophilia

Occurs in Papuloerythroderma of Ofuji

Nazarro's sign Spiky hair-like collections of paraproteins occurring on the skin of the nose of multiple myeloma patients


Microscopic Terms Characterization
Acantholysis Dyscohesion between keratinocytes from loss of the intercellular connections
Acanthosis Hyperplastic epidermis
Dyskeratosis Abnormal keratinization
Erosion Incomplete loss of the epidermis
Exocytosis Inflammatory cells infiltrating the epidermis
Granuloma Collection of epithelioid histiocytes
Hyperkeratosis Hyperplasia of the stratum corneum leading to a clinical scale
Papillomatosis Hyperplasia of the papillary dermis
Parakeratosis Retention of nuclei within the stratum corneum. It is indicative of prior spongiosis. It is a normal finding in mucous membranes
Spongiosis Intercellular edema within the epidermis
Ulceration Complete loss of the epidermis which extends into the dermis and may extend into the subcutaneous fat

Vacuoles within or adjacent to cells. Usually refers to the area of the dermal-epidermal junction

Basic Principles of Disease
Learn the basic disease classifications of cancers, infections, and inflammation

Commonly Used Terms
This is a glossary of terms often found in a pathology report.

Diagnostic Process
Learn how a pathologist makes a diagnosis using a microscope

Surgical Pathology Report
Examine an actual biopsy report to understand what each section means

Special Stains
Understand the tools the pathologist utilizes to aid in the diagnosis

How Accurate is My Report?
Pathologists actively oversee every area of the laboratory to ensure your report is

Got Path?
Recent teaching cases and lectures presented in conferences

Internet Links

Last Updated April 22, 2005

Send mail to The Doctor's Doctor with questions or comments about this web site.
Read the Medical Disclaimer.

Copyright © The Doctor's Doctor