Scalp Biopsy Specimens Research Articles

Hair counts in scalp biopsy of males and females with androgenetic alopecia compared with normal subjects

Hair counts were studied in scalp biopsy specimens of androgenetic alopecia (AGA) in male and female patients. We also assessed the normal value of hair count in scalp biopsy specimen from Iranians and compared with published data. Thirty subjects with clinically normal scalps, 25 male and 28 female patients with AGA were studied. Vertical and horizontal sections of 4-mm punch biopsy specimens were examined at various levels from the papillary dermis to the subcutis. Hair counts of total, terminal, vellus, anagen and telogen hairs were obtained by ocular micrometer. Hair counts were not significantly different from published data in American Whites but significantly higher in Iranians compared with Koreans (p < 0.001). There was no significant difference between male and female patients with AGA. Perifollicular inflammation was lower in both the normal subjects and the patients compared with other studies. In AGA patients, total and vellus hairs were lower and terminal to vellus (T:V) ratio was higher than the results of previous studies in Whites (p < 00.1). T:V ratio of control group was significantly higher in this study compared with previous published data. Perhaps the higher ratio than the reported data could means the onset of miniaturization.

Expression of hair follicle stem cells detected by cytokeratin 15 stain: implications for pathogenesis of the scarring process in cutaneous lupus erythematosus

Discoid lupus erythematosus (DLE) is a scarring disease. Although the scarring and deformity may affect any part of the body, such changes have been reported to be most obvious on the face and scalp. The pathogenesis behind this scarring process is not well understood. Once lesions have scarred, recurrent disease tends to occur at the edge of the scarred lesions but not within them. The fact that inflammation in DLE generally involves the bulge area of the follicles raises the possibility that damage to the stem cells of the bulge region may be one process leading to the permanent loss of follicles. The aim of this study was to investigate the role of the hair follicle stem cells which reside in the bulge region in the scarring process in cutaneous lupus erythematosus (CLE). We studied the reactivity of an antibody to the CD8 antigen (C8/144B), which recognizes cytokeratin (CK) 15 and preferentially immunostains hair follicle stem cells without staining the remaining hair follicle, on skin biopsies (scalp and body lesions) from patients with CLE (36 with discoid lesions and 10 with subacute lesions). Normal scalp and body biopsy specimens served as controls. The correlation between the extent of the cytotoxic inflammatory cell infiltrate (CD8+) and the presence of stem cells was investigated. Results were analysed semiquantitatively. The expression of CK15 in hair follicle stem cells was variable in the DLE lesions; there was normal to moderate CK15 expression at the bulge region of hair follicles when surrounded by mild or moderate inflammatory infiltrate (CD8+), but in cases of severe inflammation, CK15 expression was weak or absent. The bulge region appears to be involved in this disease as part of a broader involvement of the hair follicles; it is secondarily affected by the surrounding inflammatory cell infiltrate. Expression of C8/144B diminished and was then absent, indicating either damage to stem cells or differentiation to help in the repair process. Damage to follicular stem cells may help to explain the irreversible alopecia and the scarring process which characterize this disease.

Immunopathogenesis of Folliculitis Decalvans

Folliculitis decalvans (FD) is a rare variant of primary cicatricial alopecia, for which the etiopathogenesis remains unclear. Our purpose was to evaluate whether certain immunologic mechanisms might have a significant role in the pathogenesis of FD. Lesional scalp biopsy specimens from 7 patients with FD, 7 with lichen planopilaris, and 4 with alopecia areata were studied immunohistochemically by using monoclonal antibodies to CD1a, CD3, CD4, CD8, CD20, CD25, HLA-DR, interleukin (IL)-1beta, IL-4, IL-8, interferon gamma, tumor necrosis factor alpha, basic fibroblast growth factor (b-FGF), transforming growth factor (TGF)-beta, endothelial leukocyte adhesion molecule 1, intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule. We showed that early FD lesions are characterized by an infiltration of activated T-helper cells, featuring mixed TH1/TH2 polarization. IL-8 and ICAM-1 may contribute to the infiltration of neutrophils, whereas b-FGF and TGF-beta may represent important mediators of the fibrosis that characterizes late-phase FD.

A histologic review of 27 patients with lichen planopilaris

Lichen planopilaris (LPP) is a potential trichologic emergency that can result in permanent scarring alopecia. Histopathology is a key component of the diagnostic work-up. To identify the key histologic features that characterize LPP in order to facilitate diagnosis, ultimately leading to improved patient outcomes. Scalp biopsy specimens from 27 confirmed cases of LPP were reviewed in a blinded fashion to determine diagnostically helpful histologic features. Absence of arrector pili muscles and sebaceous glands, a perivascular and perifollicular lymphocytic infiltrate in the reticular dermis and mucinous perifollicular fibroplasia within the upper dermis with absence of interfollicular mucin, and superficial perifollicular wedge-shaped scarring were characterizing features. Sample size was limited, given that biopsy specimens were taken from lesions at varying stages of evolution and findings vary with disease stage. This study confirms many previously reported histologic features and highlights new characterizing features of mucinous perifollicular fibroplasia.

Value of transverse section scalp biopsy in alopecia areata - a clinicopathological correlation.

To correlate the histopathological features of alopecia areata with clinical stage by means of transverse sectioned scalp biopsy specimens, in terms of extent and duration of disease. Cross-sectional. Department of Dermatology, Combined Military Hospital, Kharian Cantonment, Pakistan, from January 2002 to December 2004. Fifty consecutive patients with alopecia areata were included in the study. Four millimeter punch biopsy was taken and representative horizontal sections from lower and upper dermis were examined. Patients were divided according to disease extent i.e. Group I (<25% of scalp surface area), Group II (25 - 75% of scalp surface area) and Group III (>75% of scalp surface area including alopecia totalis and universalis). Patients were also analyzed according to the disease duration, i.e. 0-6 months, > 6-12 months, > 1-5 years and > 5 years. Follicular unit counts and density / mm2, terminal to vellus hair ratio, anagen to telogen ratio, cellular infiltrate and fibrosis were measured to assess the diagnosis and prognosis of disease. Chi-square test was used to assess statistical significance. Diagnosis of alopecia areata could be made in 82% of biopsies. Follicular unit counts and density per mm2 decreased with the disease duration (p=0.01). Catagen and telogen hair follicle counts increased with disease duration (p=0.0001). Cellular infiltrate decreased and fibrosis increased with the duration of disease (p=0.0001). Anagen telogen ratio and terminal to vellus hair ratio inverted in long-standing disease. Transverse section scalp biopsy can help in the diagnosis of alopecia areata and the disease stage can be predicted by analyzing the histopathological findings quantitatively.

The Histopathology of Noncicatricial Alopecia

During the past 2 decades, the use of transverse sections in the evaluation of scalp biopsy specimens has led to a better understanding of the histopathologic changes in both cicatricial and noncicatricial alopecia. However, the technique has provided the most significant gains in the study of the latter type of alopecia, where evaluation of follicle density and follicular dynamics are integral to accurate diagnosis. This report reviews the histopathologic findings of four common types of noncicatricial alopecia: androgenetic alopecia, telogen effluvium, alopecia areata, and trichotillomania/chronic traction alopecia.

Possible role of the bulge region in the pathogenesis of inflammatory scarring alopecia: lichen planopilaris as the prototype

Lichen planopilaris (LPP) is the prototype of scarring alopecias that mainly target the infundibuloisthmic (bulge) region of hair follicle. Hair follicle stem cells have been shown to reside in the bulge. We carried out this study to better define the possible pathogenetic role of the bulge in LPP. Thirty-five cases of LPP were studied. Multiple serial sections of biopsy specimens stained with hematoxylin and eosin, periodic acid Schiff-diastase, and Elastic van Gieson. The following immunostains were applied: CD3, CD4, CD8, CD1a, and Ki-67. Uninvolved follicles and normal scalp biopsy specimens served as normal controls. All cases showed a lichenoid lymphocytic infiltrate at the bulge region. The bulb area was spared. CD8(+) T cells were increased compared with CD4(+) T-cell population. Langerhans' cells were decreased. Proliferating stem cells, highlighted by Ki-67, showed a marked decrease in the bulge compared with uninvolved follicles. Our study supports the finding that in LPP, the inflammatory infiltrate mainly involves the bulge region, where the stem cells reside. Once this area is damaged, the hair loses its potential of regrowth with resulting scarring alopecia. This is in contrast with inflammatory non-scarring alopecias such as alopecia areata, where the bulb region is targeted, sparing the stem cells.

Value of Direct Immunofluorescence for Differential Diagnosis of Cicatricial Alopecia

Background: There are diverse causes of cicatricial alopecia characterized by lack of follicular ostia and irreversible loss of hair. While clinical differentiation between the causes may be difficult, particularly with regard to lichen planus (LP), lupus erythematosus (LE) and pseudopelade of Brocq (PB), it has been suggested that both histopathologic examination and direct immunofluorescence studies (DIF) are necessary for an accurate diagnosis. Objective: The aim of this study was to evaluate the diagnostic value of DIF studies in addition to histopathology in patients with cicatricial alopecia as a clinical feature. Methods: 136 scalp biopsy specimens received for histopathology and DIF during a 5-year period were reviewed. Results: Definitive diagnosis was achieved by careful evaluation of scalp biopsies. The most prevalent diagnoses in order of frequency were LP (26%), LE (21%) and folliculitis decalvans (20%). PB was diagnosed in 10%. In most cases, the diagnosis could be made on the basis of histopathology and independently of DIF. Characteristic DIF patterns showed high specificity, but low sensitivity for LP, and high specificity and sensitivity for LE. The DIF pattern in PB showed no difference to LP. Conclusions: Histopathology permits diagnosis in the majority of cicatricial alopecias. DIF is of value in histopathologically inconclusive cases, particularly when LE is in question.

Chronic telogen effluvium: A study of 5 patients over 7 years

Chronic telogen effluvium is said to be self-limiting in the long run; the natural history of this condition, however, has not been investigated prospectively. Four women, aged between 18 and 64 years and diagnosed with chronic telogen effluvium between 1996 and 1997, were followed up prospectively for a minimum of 7 years. One (previously reported) woman diagnosed in 1998 developed female pattern hair loss confirmed on biopsy specimen within 18 months that was partially reversed by spironolactone. The remaining 4 women continued to experience chronic diffuse telogen hair shedding that fluctuated in severity. However, serial photography demonstrated no visible reduction in hair density, and serial scalp biopsy specimen showed no follicular miniaturization. Although 4 out of 5 of our patients showed no tendency toward development of female pattern hair loss or to spontaneous improvement, further work is required to define the natural history of chronic telogen effluvium and the relative risk of developing female pattern hair loss.

Trichotemnomania: Obsessive-compulsive habit of cutting or shaving the hair

A 28-year-old woman presented with a completely hairless scalp. The disorder had started 1 year ago, and at the same time she had developed dysphonia. During the past year, her hair disease had been diagnosed as alopecia areata totalis by many specialists, including several dermatologists. A close inspection of her scalp, however, revealed that no alopecia was present, because all infundibula were filled with a hair shaft that, on microscopic examination, showed cleanly cut surfaces. A scalp biopsy specimen showed completely normal structures. The pubic area was found to be covered with hair stubs of the same length. Therefore, a diagnosis of trichotemnomania was made. This term is derived from Greek thrix (hair), temnein (to cut), and mania (madness). After a stressful life event, the patient had developed both psychogenic dysphonia and the compulsive habit to remove the hair of her scalp, eyebrows, and axillary and pubic areas by shaving. Trichotemnomania is a distinct obsessive-compulsive disorder that should not be confused with trichotillomania. The condition should be taken into account when a supposed alopecia areata looks somewhat unusual.

Histopathologic features of alopecia areata: a new look.

A peribulbar lymphocytic infiltrate is the expected histologic feature of alopecia areata, but it is absent in many scalp biopsy specimens. Other diagnostic criteria are needed. To establish the histologic features of alopecia areata in scalp biopsy specimens taken from different types of alopecia areata, using follicular counts to relate biopsy findings to stages of the disease. Fifty consecutive new patients with alopecia areata were studied. Four-millimeter punch biopsy specimens were taken from the scalp in areas of recent, active hair loss; old, inactive hair loss; or recent hair regrowth. Specimens were sectioned horizontally. Terminal and vellus-like hairs were counted. Inflammation and fibrosis around lower and upper follicles were rated. The histopathologic features of alopecia areata were not significantly affected by the sex, age, and race of the patient or by the type, percentage of hair loss, total duration, or regression of alopecia areata. The major factor affecting the histopathologic features was the duration of the current episode of alopecia areata. In the acute stage, bulbar lymphocytes surrounded terminal hairs in early episodes and miniaturized hairs in repeated episodes. In the subacute stage, decreased anagen and increased catagen and telogen hairs were characteristic. In the chronic stage, decreased terminal and increased miniaturized hairs were found, with variable inflammation. During recovery, increasing numbers of terminal anagen hairs from regrowth of miniaturized hairs and a lack of inflammation were noted. The histopathologic features of alopecia areata depend on the stage of the current episode. Alopecia areata should be suspected when high percentages of telogen hairs or miniaturized hairs are present, even in the absence of a peribulbar lymphocytic infiltrate.

Hair counts from scalp biopsy specimens in Asians

Background: Differences in hair density have been described according to the ethnic background in whites and blacks. Asians are known to have fewer hairs than whites. Objective: We performed this study to assess the normal values of hair counts in scalp biopsy specimens from Koreans. Methods: A total of 35 subjects with clinically normal occipital scalps (13 patients with androgenetic alopecia, 20 with patchy alopecia areata, and 2 healthy volunteers) were included. Horizontal sections of 4-mm punch biopsy specimens from clinically normal occipital scalps were examined at various levels from the papillary dermis to the subcutis, and follicular counts of terminal/vellus hairs and anagen/telogen hairs were obtained. Results: The numbers of total hairs, terminal and vellus hairs, and terminal anagen hairs were significantly lower (P < .05) in Koreans compared with the published data of whites and blacks. Percent ratio of terminal anagen and telogen hairs were similar to whites and blacks. Follicular density was significantly lower (P < .05) in Koreans than in whites and blacks. In Koreans, female subjects had a significantly higher number of terminal hairs than male subjects (P < .05). Conclusion: Hair density is significantly lower in Koreans than in whites or blacks. Slight sexual difference exists in follicular counts in Koreans. Our data could be used as a guideline for determining normalcy in interpreting horizontal sections of scalp biopsy specimens from Asians. (J Am Acad Dermatol 2002;46:218-21.)

Why steroids may not always work in alopecia areata: elevated unoccupied glucocorticoid receptors and decreased levels of thioredoxin

Alopecia areata (AA) patients show a variable response in hair regrowth with glucocorticoid (GC) steroid treatment. The biochemical mechanisms by which GCs stimulate hair growth in patients with AA is unknown, yet clinicians commonly use topical, intralesional, and even oral GC steroid therapy to treat AA. In this study, scalp biopsy specimens were obtained from 15 patients (in each group) with extensive AA, male androgenetic alopecia (AGA), and normal controls (N), and were analyzed for GC receptor (GCR) content. All patients were off therapy at the time they were studied. Tissue samples were assessed for total, occupied, and unoccupied GCR type I and II binding. Results from patients with AA show that the type II GCR is elevated and in an unoccupied state compared to AGA and N patient biopsies (p < 0.01). A factor known to activate the GCR, called thioredoxin (TR), was decreased in AA scalp compared to N and AGA (p < 0.01). Finding elevated unoccupied type II GCR with diminished TR levels indicates inhibition of cellular transcription. This may be important in explaining the variable responses seen with GC treatment for hair regrowth in patients with AA and gives the clinician possible reasons why steroids may not always be effective in treating this difficult hair disease.

Scarring alopecia and the dermatopathologist.

The evaluation of patients with cicatricial alopecia is particularly challenging, and dermatopathologists receive little training in the interpretation of scalp biopsy specimens. Accurate interpretation of specimens from patients with hair disease requires both qualitative (morphology of follicles, inflammation, fibrosis, etc.) and quantitative (size, number, follicular phase) information. Much of this data can only be obtained from transverse sections. In most cases, good clinical/pathologic correlation is required, and so clinicians should be expected to provide demographic information as well as a brief description of the pattern of hair loss and a clinical differential diagnosis. The criteria used to classify the various forms of cicatricial alopecia are relatively imprecise, and so classification is controversial and in a state of evolution. There are five fairly distinctive forms of cicatricial alopecia: 1) chronic, cutaneous lupus erythematosus (discoid LE); 2) lichen planopilaris; 3) dissecting cellulitis (perifolliculitis abscedens et suffodiens); 4) acne keloidalis; and 5) central, centrifugal scarring alopecia (follicular degeneration syndrome, folliculitis decalvans, pseudopelade). Not all patients with cicatricial alopecia can be confidently assigned to one of these five entities, and "cicatricial alopecia, unclassified" would be an appropriate label for such cases. The histologic features of five forms of cicatricial alopecia are reviewed. Dermatopathologists can utilize a "checklist" to catalog the diagnostic features of scalp biopsy specimens. In many, but not all, cases the information thus acquired will "match" the clinical and histologic characteristics of a form of cicatricial alopecia. However, because of histologic and clinical overlap between the forms of cicatricial alopecia, a definitive diagnosis cannot always be rendered.

Lack of efficacy of finasteride in postmenopausal women with androgenetic alopecia

Background: Finasteride, an inhibitor of type 2 5α-reductase, decreases serum and scalp dihydrotestosterone (DHT) by inhibiting conversion of testosterone to DHT and has been shown to be effective in men with androgenetic alopecia (AGA). The effects of finasteride in women with AGA have not been evaluated. Objective: The purpose of this study was to evaluate the efficacy of finasteride in postmenopausal women with AGA. Methods: In this 1-year, double-blind, placebo-controlled, randomized, multicenter trial, 137 postmenopausal women (41-60 years of age) with AGA received finasteride 1 mg/day or placebo. Efficacy was evaluated by scalp hair counts, patient and investigator assessments, assessment of global photographs by a blinded expert panel, and histologic analysis of scalp biopsy specimens. Results: After 1 year of therapy, there was no significant difference in the change in hair count between the finasteride and placebo groups. Both treatment groups had significant decreases in hair count in the frontal/parietal (anterior/mid) scalp during the 1-year study period. Similarly, patient, investigator, and photographic assessments as well as scalp biopsy analysis did not demonstrate any improvement in slowing hair thinning, increasing hair growth, or improving the appearance of the hair in finasteride-treated subjects compared with the placebo group. Finasteride was generally well tolerated. Conclusion: In postmenopausal women with AGA, finasteride 1 mg/day taken for 12 months did not not increase hair growth or slow the progression of hair thinning. (J Am Acad Dermatol 2000;43:768-76.)

Alopecia Areata with Features of Loose Anagen Hair

A child with alopecia areata (AA) presented initially with clinical features of loose anagen hair (LAH) and had features consistent with LAH on microscopic hair analysis. However, a scalp biopsy specimen demonstrated peribulbar inflammatory infiltrates characteristic of AA. We suggest that AA may mimic LAH clinically and a scalp biopsy may help in making the correct diagnosis.

Hair density in African Americans.

The meager data on normal hair density in humans have been gathered from a predominantly white population. Examination of scalp biopsy specimens from African Americans suggests that hair density in this group may be lower than in whites. This study was performed to quantify any differences between white and African American patients. A retrospective case series of subjects who had undergone a biopsy of clinically healthy scalp skin. The 4-mm punch biopsy specimens were sectioned, and all follicles contained within the specimens were counted at various levels (suprabulbar, isthmus, and infundibulum) to arrive at the number and type of hairs present. Outpatient clinic in a tertiary care medical center. A consecutive sample of 22 African American and 12 white patients with clinically healthy scalp skin specimens that were studied and compared with previously reported data. Patients' age and total number of follicles, terminal follicles, vellus follicles, terminal anagen hairs, and terminal telogen hairs. Total hair density (number of follicles per 4-mm punch biopsy specimen) and total number of terminal follicles and terminal anagen hairs were significantly lower in African Americans (P<.001) than in whites and in a previously reported, predominantly white, population. Hair density in African Americans is significantly lower than that in whites, which must be taken into consideration when evaluating a biopsy specimen from an African American patient. Data previously collected from white patients may not provide adequate guidance when evaluating scalp biopsy specimens from African Americans and could lead to an incorrect diagnosis.

Transverse scalp sections: A proposed method for laboratory processing

Background: Transverse sections of human scalp biopsy specimens can provide both qualitative and quantitative information about follicular histopathology not readily available in vertically sectioned specimens. Objective: We propose a method for making the processing and interpretation of such specimens easier. Methods: All scalp biopsy specimens obtained during the past 18 months in our institution for the evaluation of alopecia were processed for transverse sections by means of a technique employing trisection or quadrisection (rather than the standard bisection), and maintaining all sections in the same anatomic orientation (deep to superficial) in all tissue pieces on microscopic slides. Results: More than 120 transversely sectioned specimens from more than 75 patients have been processed with this technique. The typical number of slides cut per specimen decreased from between 12 and 20 to between 1 and 4, with no loss of clinical information. Conclusion: This technique allows transverse sections for evaluation of alopecia to be processed in a more cost-effective manner and compares favorably with previously published techniques in providing diagnostic information.

Clinical and histopathologic features of hair loss in patients with HIV-1 infection

Background: Hair loss is common in patients with HIV-1 infection, and in black patients this loss may be associated with straightening. Possible causes are frequently present in patients with HIV-1. These causes include chronic HIV-1 infection itself and recurrent secondary infections, nutritional deficiencies, immunologic and endocrine dysregulation, and exposure to multiple drugs. However, histopathologic features have rarely been reported in these patients. Objective: The objective was to evaluate the changes in the hairs of a group of these patients and to identify the light microscopic and ultrastructural changes in the hairs and the histologic changes in the scalp. Methods: Hair plucks and pulls with scanning electron microscopy of the hairs were done on 10 patients with late-stage HIV-1 infection. In addition, scalp biopsy specimens were examined in both vertical and transverse sections. Results: All patients had telogen effluvium. Numerous apoptotic or necrotic keratinocytes were seen in the upper external root sheath follicular epithelium in addition to a mild to moderate perifollicular mononuclear cell infiltrate often containing eosinophils. Variable dystrophy of the hair shafts was also a consistent feature. Conclusion: Although telogen effluvium is a common response to a wide spectrum of biologic stresses, the presence of apoptotic or necrotic keratinocytes within the upper end of the external root sheath epithelium and dystrophy of hairs may be markers of hair loss in patients with HIV-1 infection.

Vertical and transverse sections of alopecia biopsy specimens: Combining the two to maximize diagnostic yield

Background: Traditional vertical sections of scalp biopsy specimens contain few hair follicles. For this reason transverse sections of scalp biopsy specimens have been advocated. Both methods have advantages and disadvantages. We have developed a simple method that we believe offers the best of both methods. Objective: Our purpose was to assess the impact of combining vertical and transverse sections of scalp biopsy specimens. Methods: Two 4 mm punch biopsies are performed. One specimen is bisected vertically: half for hematoxylin-eosin (H-E) staining, half for direct immunofluorescence. The second specimen is bisected transversely and submitted for H-E. The three pieces of tissue for H-E staining are embedded in a single cassette. Results: Because a biopsy specimen for direct immunofluorescence is commonly obtained in cases of alopecia, our method does not add a surgical procedure. All three pieces of tissue for H-E staining are embedded in a single paraffin block. Therefore the cost of histologic interpretation is not increased. Our diagnostic yield improved. Transverse sections were superior in cases of lupus erythematosus and lichen planopilaris with focal follicular involvement. Features of the follicular degeneration syndrome were also best demonstrated in transverse sections. Interface changes, lupus panniculitis, miniaturized hairs, and trichomalacia were better demonstrated in vertical sections. Conclusion: Our method exploits the advantages of both vertical and transverse sections and improves diagnostic yield without increasing cost.