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PIILIF in Dissecting Cellulitis: What Paired Biopsies Reveal Across Normal-Appearing Scalp, Quiet Nodules and Active Lesions

A technical, implementation-focused summary of a paired-biopsy study examining the clinical, histologic and immunophenotypic expression of PIILIF across dissecting cellulitis disease states.

Clinical premise

Dissecting cellulitis of the scalp is conventionally classified as a neutrophilic primary cicatricial alopecia characterized by follicular occlusion, rupture, abscess formation, sinus tracts, granulation tissue and scarring.

Those features define active destructive disease. They do not fully account for:

The study tested whether PIILIF, an upper-follicle lymphocytic-fibrotic pattern previously described in clinically normal-appearing scalp in other cicatricial alopecias, was also present in DCS outside actively suppurative lesions. 

Study rationale and cohort

This was a retrospective, exploratory, single-center clinicopathologic study of consecutive patients with clinicopathologically concordant DCS evaluated from December 2022 through November 2024.

The cohort included:

Each patient underwent a protocolized paired-biopsy evaluation during routine care. 

Biopsy-site definitions

Clinically normal-appearing scalp, or cNAS

Scalp without visible:

The area was normal on inspection and palpation at the time of biopsy.

Trichoscopy was used to identify subtle perifollicular abnormalities, including mild erythema, hyperpigmentation or scale, to guide site selection. The cNAS biopsy was typically obtained from parietal scalp approximately 2 to 3 cm from the nearest clinically evident lesion. 

Active DCS lesion

A lesion showing one or more of the following:

Clinically inactive, or quiet, nodule

A residual indurated nodule without signs of active inflammation.

Paired-biopsy method

Each patient underwent:

  1. A 6 mm punch biopsy from cNAS 
  2. A second 6 mm punch biopsy from an active DCS lesion or, when no active lesion was present, a clinically inactive nodule 

Both specimens were obtained from the same scalp during the same clinical evaluation.

The paired design allowed comparison of the clinically visible disease state with scalp that appeared unaffected in the same patient. 

Sectioning and histopathologic assessment

Each specimen was processed with both:

Vertical sections were used to assess upper-follicle inflammation, while transverse sections improved visualization of concentric perifollicular fibrosis and adnexal loss.

PIILIF was defined as:

Two board-certified dermatopathologists independently reviewed the slides while blinded to clinical information, sampling site, lesion activity and treatment history. Differences were resolved by consensus. 

Immunohistochemistry

The study used:

Immunohistochemistry was evaluable in eight active-lesion and cNAS pairs.

Across disease states:

The findings support an immunologically active upper-follicle process rather than nonspecific end-stage scar alone. 


Findings across the three sampled states


Clinical state
PIILIF finding
Suppurative or destructive findings
Sebaceous gland finding

Normal-appearing scalp
Present in 12 of 12 biopsies
No neutrophilic infiltrates in the nine matched comparisons; no granulation tissue
No complete gland loss in the nine matched comparisons

Clinically inactive nodules
Present in 3 of 3 nodules
No destructive suppurative features identified
Sebaceous glands preserved

Active DCS lesions
Infundibulo-isthmic fibrosis in 9 of 9; lymphocytes in 8 of 9
Neutrophils in 9 of 9; granulation tissue in 5 of 9; follicular destruction or rupture in 6 of 9
Complete gland loss in 6 of 9


Active lesions therefore showed classic neutrophilic destruction and tissue remodeling superimposed on an upper-follicle PIILIF background. 

Interpretation

A possible field effect

The presence of PIILIF in cNAS, quiet nodules and active lesions supports a field-effect hypothesis in which low-grade upper-follicle inflammation and early fibrosis extend beyond clinically obvious DCS margins.

This model could help explain relapse, extension and overlap with other folliculocentric disorders.

It remains associative. The study cannot establish whether PIILIF precedes, follows or persists after active DCS lesions. 

A possible two-layer inflammatory model

The findings support a working model in which:

  1. A chronic lymphocytic-fibrotic upper-follicle pattern is present across a wider scalp field 
  2. Episodic neutrophil-dominant activation produces follicular rupture, pus, granulation tissue, gland loss and scarring 

This model is hypothesis-generating and was not directly tested mechanistically.

The sebaceous-gland distinction

Sebaceous glands were preserved in cNAS and quiet nodules but completely absent in six of nine active lesions.

This separation raises the hypothesis that sebaceous gland loss may mark a transition toward less reversible disease.

The cross-sectional design cannot prove that sequence. A quiet nodule may represent:

Three patients had previously been managed as having seborrheic dermatitis, but none of the study biopsies supported that diagnosis.

This supports a low threshold for reconsidering the diagnosis when persistent perifollicular erythema or scale does not fit the clinical course.

Prior antifungal or corticosteroid exposure may have attenuated seborrheic dermatitis findings, so the study does not establish that every previous dandruff diagnosis was incorrect. 

Overlap with AKN and disease beyond the scalp

Concurrent histologic AKN was present in three of 12 patients. PIILIF was also found in a sideburn specimen from one patient.

These observations support investigation of broader folliculocentric susceptibility in selected patients, but they are too limited to establish prevalence or a universal overlap phenotype. 

One-Page Paired-Biopsy Request Guide

Research-informed protocol based on the published study. This is not a formal consensus guideline and should be adapted to the clinical question.

Clinical indication

Consider a paired-biopsy approach when evaluating:

Specimen A: Clinically normal-appearing scalp

Select a site that has:

Preferred study location:

Specimen B: Lesional scalp

When active disease is present, target a lesion showing:

When no active lesion is present, target:

Collection

Processing request

Request:

Histopathologic features to assess

For both specimens:

For active lesions:

Suggested ancillary stains

When tissue is sufficient and clinically appropriate:

Suggested requisition wording

Clinical history of recurrent or suspected dissecting cellulitis. Paired specimens submitted from clinically normal-appearing scalp and an active lesion or clinically inactive nodule. Please evaluate for perifollicular infundibulo-isthmic lymphocytic inflammation and fibrosis, sebaceous gland status, follicular rupture, neutrophilic inflammation, granulation tissue and scarring. Please process with vertical and transverse sections. Consider alpha-SMA, CD4, CD8 and CD117 if tissue and findings permit.

Limitations

The study’s main limitations include:

The 100% cNAS finding should therefore not be interpreted as proof that PIILIF is universal or specific to all DCS cases. 

Unanswered research questions

The publication creates several testable questions:

  1. Does PIILIF in cNAS precede the development of visible DCS lesions? 
  2. Does the burden or distribution of PIILIF predict extension or relapse? 
  3. Does sebaceous gland loss mark a transition toward less reversible disease? 
  4. Are quiet nodules early lesions, partially controlled lesions or post-destructive remnants? 
  5. What molecular event converts a lymphocytic-fibrotic field into a neutrophil-dominant flare? 
  6. How do DHT signaling, cytokine activity, mast cells, microbiome changes and follicular rupture interact? 
  7. Is PIILIF specific to DCS or shared across a broader group of cicatricial alopecias? 
  8. Does addressing PIILIF in addition to suppressing active neutrophilic inflammation improve long-term outcomes? 

Prospective longitudinal studies with standardized clinical scores, serial paired biopsies, healthy or disease controls, quantitative pathology and spatial immune analysis are needed. Interventional studies will be required before any treatment-specific conclusions can be made. 

Refer a DCS Case

The clinician referral form should request:

Refer a DCS Case

Request the Paired-Biopsy Protocol

Provide a downloadable one-page PDF version of the protocol above, with:

Request the Paired-Biopsy Protocol

Express Interest in a Multicenter PIILIF Study

The collaboration form should request:

Express Interest in a Multicenter PIILIF Study

Publication

Perifollicular Lymphocytic Inflammation and Fibrosis in Dissecting Cellulitis: Evidence of a Consistent Histopathologic Pattern

Published in Clinical, Cosmetic and Investigational Dermatology on July 17, 2026. 

Publication-Link Implementation

Link the full paper title on both pages to: https://doi.org/10.2147/CCID.S614816