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ALOPECIA - Marc R. Lewin, M.D.


ALOPECIA

Alopecia is a commonly encountered condition which can be frustrating for patients and clinicians alike as it is often difficult to make a definitive diagnosis. However, a proper clinicopathologic approach to alopecia greatly enhances the specificity and diagnostic yield of scalp biopsies for alopecia.

This Focus issue outlines an approach to alopecia biopsies which attempts to maximize their diagnostic yield. A short review of some of the more commonly encountered alopecias will also be included in a bullet format.

Clinical Correlation
As with many areas in the realm of Dermatopathology, clinical correlation is critical in order to arrive at the most specific diagnosis. Often times, the submitted clinical information may be as obscure as “alopecia” or “scarring versus non scarring.”

As there is often histologic overlap and a wide spectrum of findings within each type of alopecia, the clinical findings may greatly affect the dermatopathologist’s ability to interpret the biopsy findings. For example, the inactive phase of alopecia areata and androgenic alopecia my have histological identical findings, and the clinical findings may be the key to differentiating these conditions.

Therefore, submitting as much clinical information (such as: scarring versus non-scarring clinically; is there clinical inflammation or pustule formation; the distribution of hair loss; the duration of hair loss; and whether the hair loss is patterned or diffuse) on the requisition greatly enhances the probability that a specific diagnosis will be made.
 
Biopsy
In approaching a scalp biopsy for alopecia, determining the appropriate site of biopsy is often crucial to establishing a correct diagnosis. For a scarring process, biopsies taken from the peripheral edge of the lesion are more likely to display diagnostic findings. Often times, two biopsies may be of benefit in order to enable both horizontal and vertical sectioning (see below). In the setting of a potential discoid lupus case, a second biopsy processed for immunofluorescence studies in Michel’s media may also be beneficial.

For non-scarring alopecias, the preferred site of biopsy is generally the border of a patterned alopecia, or from the site of a positive pull test in the setting of a diffuse alopecia. In the setting of evaluating a possible androgenic alopecia from a telogen effluvium, two biopsies, one from the involved scalp (often vertex) and one from the uninvolved scalp (often occiput) may be beneficial. The biopsy from the occiput serves as a positive control of the patient’s hair characteristics as this area is generally non androgen dependent.

Vertical vs Horizontal Sectioning
In general there is some debate as to whether alopecia biopsies are better sectioned vertically or horizontally (transversely).

Vertical sectioning is useful for evaluation of alopecias associated with interface changes, lichenoid infiltrates, and for evalutating the full thickness of the skin in every section, a feature that is useful for evaluation in scarring alopecias. However, the downside is that vertical sectioning will only show approximately 10% of the overall follicles present in the section, and as the diagnostic findings in alopecia are often focal, they may be missed due to the high sampling era inherent to this technique.

Horizontal sectioning is now the generally accepted and preferred method for evaluating alopecias. It allows detection of follicular pathology even when the findings are focal, as it allows all of the follicles within the specimen to be examined. In addition, it allows for a quantitative approach to the analysis of biopsies, as various criteria can be analyzed (follicular anagen counts; telogen/catogen counts; terminal to vellus hair ratio, etc).

However, in order for horizontal sectioning to be effective the biopsy must be a 4mm punch which includes subcutaneous tissue. All of the published criteria and ratios have been based on 4mm punch biopsies, and thus, a 4mm punch biopsy is essential in order to employ a truly analytical and quantitative approach to hair biopsies.

At ProPath, horizontally sectioning of a 4 mm punch is the generally preferred technique in dealing with an alopecia biopsy. However, each alopecia biopsy is generally evaluated by a dermatopathologist, and based on the clinical information, size of the biopsy, and other factors, the specimen is processed in a way which is felt will yield the highest possible diagnostic yield.

Summary of commonly encountered alopecias:
TABLE 1: SCARRING ALOPECIAS

 

CLINICAL  HISTOLOGICAL
 
Lichen planopilaris (LPP) 
Generally presents as scattered foci of partial hair loss.  Perifollicular erythema and scaling are common to all cases.  Findings include an interface lichenoid dermatitis most prominently Affecting the infundibular portion of the follicle.  Later in the process there is often peri-folliclular inflammation and fibroplasia.
 
Central Centrifugal Scarring Alopecia (CCCA) 
Often presents in African American females as a progressive, permanent loss of scalp hair starting on the central crown.   Findings include premature desquamation of the inner root sheath, and eccentric epithelial thinning with hair shafts in close proximity to the dermis.
 
Discoid Lupus Erythematosus (DLE) 
Classic DLE lesions include alopecia with erythema, epidermal atrophy and plugged follicles.  Vacuolar interface change of the follicle and epidermis; periadnexal infiltrate; Perifollicular fibrosis; Granular IgG/C3 at dermoepidermal junction on immunofluorescence. 
 
Pustulofolliclular Alopecias 
Includes a variety of entities including folliculitis decalvans, dissecting cellulitis, and acne keloidalis.   These entities generally begin as predominantly neutrophilic dermal and follicular infiltrates which generally progress to scarring alopecias. In later stages, the neutrophilic infiltrate subsides and often there is a plasma cell rich infiltrate in the setting of a scarring alopecia. 


TABLE 2: NON SCARRING ALOPECIAS

CLINICAL  HISTOLOGICAL
 
Androgenetic Alopecia
 
Symmetric thinning affecting crown, vertex, and frontal regions with sparing of the occiput.   Normal total number of follicles with prominent miniaturization of follicles and mildly increased telogen/catogen count. No prominent inflammation.
 
Alopecia Areata 
Patchy or well circumscribed loss of hair; exclamation mark hairs may be seen.  Normal total number of follicles; peribulbar lymphocytic infiltrate (“swarm of bees’); eosinophils may be present; increased terminal/catogen hairs; increased miniaturized hairs.
 
Telogen Effluvium 
Diffuse hair loss often with a precipitating clinical event.  Normal total number of hairs with normal terminal: vellus ratio;Marked increase in terminal telogen hairs.
 
Trichotillomania 
Often children.  Irregular shaped lesions with sharp margins.   Trichomalacia and pigmented casts; distorted hair anatomy; increased telogen/catogen hairs.

References:
1. Boer, A. and K. Hoene, Transverse sections for diagnosis of alopecia? Am J Dermatopathol, 2005. 27(4): p. 348-52.

2. Eudy, G. and A.R. Solomon, The histopathology of noncica tricial alopecia. Semin Cutan Med Surg, 2006. 25(1): p. 35-­40.


3. Han, A. and P. Mirmirani, Clinical approach to the patient with alopecia. Semin Cutan Med Surg, 2006. 25(1): p. 11-­23.


4. Sperling, L.C., An Atlas of Hair Pathology with Clinical Correlations. 2003, New York: The Parthenon Publishing Group.

5. Stefanato, C.M., Histopathology of alopecia: a clinicopatho logical approach to diagnosis. Histopathology. 56(1): p. 24-­38.