Reflections on reflectance confocal microscopy for diagnosing benign lichenoid keratoses
By Warren R. Heymann, MD, FAAD
July 5, 2023
Vol. 5, No. 27
At the inception of my dermatology residency in July 1980 I read a brief article entitled “Benign Lichenoid Keratosis” (BLK) by Detlef Goette (1) and thought to myself “Remember this — I’ll probably see this lesion now and then.” That proved to be the understatement of my career. Clinically, BLKs may resemble a basal cell carcinoma, actinic keratosis, Bowen’s disease, or an amelanotic melanoma. How many thousands of biopsies have I performed because of my uncertainty of the diagnosis of a BLK?
Dermatologists are intimately familiar with BLKs, aka lichenoid keratoses (LKs) or lichen planus-like keratoses (LPLKs). It is hard to fathom that these lesions were new and controversial, being introduced to the dermatology world in 1966 in 2 articles — a year prior to Super Bowl I when the Green Bay Packers trounced the Kansas City Chiefs. Lumpkin and Helwig detailed 10 patients with solitary lesions with histologic features of lichen planus (LP) although none were considered LP clinically. The authors questioned whether these lesions represented a distinct entity or were a forme fruste of LP. (2) Identical lesions were described as a solitary lichen planus-like keratosis (SLPLK) by Shapiro and Ackerman. (3) In 1976, Mehregan concluded that SLPLKs are an inflammatory reaction against the central aspect of “lentigo senilis” with pigment retained at the periphery of the lesion, as observed in 50 cases. (4)
In his review of 1,366 cases, Vincek observed that LPLK occurs mostly as a single lesion (97%) with the chest (41.4%) being the most common site. It is almost equally present in women and men (51.5%-48.5%). (5) LPLKs characteristically appear between the 5th and 6th decades of life and may also be observed on the face and upper arms. Lesions usually appear as a solitary pink, red, or gray macule, papule, or plaque. (6) Presentations may vary in different populations. In a study of 81 patients from Iran and Turkey, there was a greater frequency of pigmented variants, a lower incidence in females, and a lower prevalence on the torso, in favor of the face. (7) An acute presentation of multiple LPLKs has been reported with the use of the PD-LI inhibitor avelumab for Merkel cell carcinoma (8) and R-CHOP 21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) for treating a diffuse large B-cell lymphoma. (9) The pathogenesis of LPLKs remains speculative. The majority of cases are due to regression of lentiginous lesions, but what triggers that phenomenon remains to be defined.
Histologically, the lesions resemble lichen planus by demonstrating vacuolar alteration, Civatte bodies, and a band-like mononuclear infiltrate containing melanophages. One of the more challenging dermoscopic findings are gray dots correlating with melanophages, as might be observed in melanoma. (6) This diagnostic insecurity usually results in a biopsy. Even more aggravating is receiving a histologic report stating that only macrophages are observed, in which case a regressed melanoma cannot be ruled out. That’s a lot of worry and cost for a benign lesion. Is there a better way to confidently diagnose BLKs?
The impetus of this commentary was the Elson B. Helwig memorial lecture delivered at the 2022 American Society of Dermatopathology by Jane Grant-Kels, entitled “Through the Looking Glass – A Dermatopathologist’s View of Dermoscopy and Confocal Microscopy” — I was gobsmacked by her presentation. Prior to this lecture, I never paid much attention to reflectance confocal microscopy (RCM) for multiple reasons — availability, cost of the equipment, and interpreting horizontal sections in black and white. RCM is a high-resolution, noninvasive tool that is currently approved by the FDA for obtaining and interpreting images of the skin and cutaneous neoplasms with the goal of decreasing unnecessary biopsy procedures in patients with benign lesions. There are RCM criteria for benign lesions (melanocytic nevus, solar lentigo, seborrheic keratosis, sebaceous hyperplasia, and LPLK) and malignant tumors (basal cell carcinoma, squamous cell carcinoma, and melanoma). Major RCM features of LPLK are a) a regular honeycomb pattern of the spinous and granular layers; b) foci of elongated bright cords with bulbous projections at the dermoepidermal junction; c) other foci with an abrupt transition between the epidermis and dermis representing flattening of the dermoepidermal junction; and d) numerous bright dots and plump-bright cells in the papillary dermis corresponding to melanophages. (10) Cases reported by Mazzilli et al demonstrate how dermoscopy may be equivocal compared to RCM in securing the diagnosis of LPLKs. (11)
Once the diagnosis of BLK is rendered, treatment may vary from reassurance to any of your favorite destructive modalities (cryosurgery, electrosurgery, laser, etc.).
As I was performing a biopsy on a presumed BLK, a patient asked me to repeat the name. His response charmed me: “Now I understand, because I’m like annoyed by this.” As RCM becomes more available, that technique, and newer diagnostic techniques such as 2-photon fluorescence microscopy, will render skin biopsies obsolete in many situations, thereby annoying our patients less frequently.
Point to Remember: Reflectance confocal microscopy may obviate the need for biopsies of benign lichenoid keratoses (and other lesions).
Our expert’s viewpoint
Jane M. Grant-Kels, MD, FAAD
Professor of Dermatology, Pathology, and Pediatrics
Vice Chair, Department of Dermatology
Director, Cutaneous Oncology Center and Melanoma Program
Assistant Residency Program Director
University of Connecticut
Adjunct Clinical Professor
University of Florida Dermatology Department
I was incredibly flattered to read that Dr. Heymann was “gobsmacked” by my ASDP Helwig Memorial lecture that I entitled “Through the Looking Glass.”
I have been a clinical dermatologist and dermatopathologist for 44 years. Despite my age, gray hair, and experience, I remain challenged by LPLKs, especially those located on the face. Although I am very adept with the dermatoscope, even the dermatoscope often fails me as there are many overlapping dermoscopic features between LPLKs, pigmented actinic keratoses (AKs) / Bowen’s disease, and lentigo maligna (LM). We all know that our patients do not consider a biopsy of their face trivial nor are they happy with a facial scar from an unnecessary biopsy of a benign lesion. I must admit that I had begun to feel a personal sense of failure when I had to call a patient relaying the good news that the biopsy from their face only showed a histologic benign lichenoid keratosis with the unspoken bad news that they may get a scar from the now obviously unnecessary biopsy.
The reflectance confocal microscope (RCM) has come to my rescue. For facial lesions that clinically and dermoscopically leave me feeling stymied and stuck with the differential of an LPLK, pigmented AK or Bowen’s vs. LM, I pull out the RCM which is on wheels and easily rolled into the patient room. Instead of being assaulted by my scalpel, the lesion is imaged at the exam table while I am seeing another patient in another room. When the images are acquired, I return to the exam room, review the images with the patient, and either reassure them that they have a benign lesion, or show them the changes on confocal that concern me. In an ideal world where scheduling was more flexible, the lesion in question could be excised on the spot with a 5mm margin, sent for Mohs surgery, or surgery could be avoided completely, and the patient could be treated with a topical chemotherapeutic or immunotherapeutic cream.
I hope that my experiences will cause others to consider learning more about RCM and how it can improve their practice, help their patients, and cause us all to reduce unnecessary biopsies!
Goette DK. Benign lichenoid keratosis. Arch Dermatol. 1980 Jul;116(7):780-2. PMID: 7396541.
Lumpkin LR, Helwig EB. Solitary lichen planus. Arch Dermatol. 1966 Jan;93(1):54-5. PMID: 5900703.
Shapiro L, Ackerman AB. Solitary lichen planus-like keratosis. Dermatologica. 1966;132(5):386-92. doi: 10.1159/000254438. PMID: 5922272.
Mehregan AH. Lentigo senilis and its evolutions. J Invest Dermatol. 1975 Nov;65(5):429-33. doi: 10.1111/1523-1747.ep12608175. PMID: 127813.
Vincek V. Lichen planus-like keratosis: clinicopathological evaluation of 1366 cases. Int J Dermatol. 2019 Jul;58(7):830-833. doi: 10.1111/ijd.14358. Epub 2018 Dec 18. PMID: 30565224.
Pogorzelska-Antkowiak A. Lichen planus-like keratosis: what do we know about it? Clin Exp Dermatol. 2022 Nov;47(11):1923-1927. doi: 10.1111/ced.15318. PMID: 35775867.
Ansari MS, Akay BN, Cengiz FP, Rosendahl N, Mahmoudi H, Daneshpazhooh M, Rosendahl C. Clinical and dermatoscopic characteristics of lichen planus-like keratosis in a West-Asian population. Australas J Dermatol. 2021 Feb;62(1):e55-e61. doi: 10.1111/ajd.13455. Epub 2020 Nov 17. PMID: 33200822.
Cardis MA, Jiang H, Strauss J, Gulley JL, Brownell I. Diffuse lichen planus-like keratoses and clinical pseudo-progression associated with avelumab treatment for Merkel cell carcinoma, a case report. BMC Cancer. 2019 Jun 4;19(1):539. doi: 10.1186/s12885-019-5759-1. PMID: 31164102; PMCID: PMC6549366.
Pitney T, Pitney MJ. Eruptive lichen planus-like keratoses induced during R-CHOP 21 chemotherapy for diffuse large B-cell (gastric) lymphoma. Australas J Dermatol. 2021 Aug;62(3):e446-e447. doi: 10.1111/ajd.13573. Epub 2021 Mar 4. PMID: 33660843.
Shahriari N, Grant-Kels JM, Rabinovitz H, Oliviero M, Scope A. Reflectance confocal microscopy: Diagnostic criteria of common benign and malignant neoplasms, dermoscopic and histopathologic correlates of key confocal criteria, and diagnostic algorithms. J Am Acad Dermatol. 2021 Jan;84(1):17-31. doi: 10.1016/j.jaad.2020.05.154. Epub 2020 Jun 18. PMID: 32565210.
Mazzilli S, Cosio T, Campione E, Gonzalez S, Lanna C, Di Prete M, Velasco V, Bianchi L. Lichenoid Keratosis: A Clinical Trap without Secrets for Reflectance Confocal Microscopy. Case Rep Dermatol. 2020 Mar 20;12(1):47-51. doi: 10.1159/000506669. PMID: 32308575; PMCID: PMC7154274.
Waldman A, Evans CL. Future Potential of 2-Photon Fluorescence Microscopy in Mohs and General Dermatology Practice. JAMA Dermatol. 2022 Oct 1;158(10):1123-1124. doi: 10.1001/jamadermatol.2022.3510. PMID: 36069853.
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