Appropriate use criteria for ancillary diagnostic testing in dermatopathology: New recommendations for 11 tests and 220 clinical scenarios from the American Society of Dermatopathology Appropriate Use Criteria Committee.

BACKGROUND: Appropriate use criteria (AUC) provide patient-centered physician guidance in test selection. An initial set of AUC was reported by the American Society of Dermatopathology (ASDP) in 2018. AUC reflect evidence collected at single timepoints and may be affected by evolving evidence and experience. The objective of this study was to update and expand AUC for selected tests. METHODS: RAND/UCLA (RAND Corporation [Santa Monica, CA]/University of California Los Angeles) methodology used includes the following: (a) literature review; (b) review of previously rated tests and previously employed clinical scenarios; (c) selection of previously rated tests for new ratings; (d) development of new clinical scenarios; (e) selection of additional tests; (f) three rating rounds with feedback and group discussion after rounds 1 and 2. RESULTS: For 220 clinical scenarios comprising lymphoproliferative (light chain clonality), melanocytic (comparative genomic hybridization, fluorescence in situ hybridization, reverse transcription polymerase chain reaction, telomerase reverse transcriptase promoter), vascular disorders (MYC), and inflammatory dermatoses (periodic acid-Schiff, Gömöri methenamine silver), consensus by panel raters was reached in 172 of 220 (78%) scenarios, with 103 of 148 (70%) rated "usually appropriate" or "rarely appropriate" and 45 of 148 (30%), "appropriateness uncertain." LIMITATIONS: The study design only measures appropriateness. Cost, availability, test comparison, and additional clinical considerations are not measured. The possibility that the findings of this study may be influenced by the inherent biases of the dermatopathologists involved in the study cannot be excluded. CONCLUSIONS: AUC are reported for selected diagnostic tests in clinical scenarios that occur in dermatopathology practice. Adhering to AUC may reduce inappropriate test utilization and improve healthcare delivery.

Cutaneous perivascular epithelioid cell tumor (PEComa): case report and world literature review of clinical and molecular characteristics.

Perivascular epithelioid cell tumor (PEComa) expresses melanocytic and smooth muscle markers. A man with a primary malignant cutaneous (distal left forearm) PEComa is reported. Immunohistochemistry demonstrated MiTF, HMB-45, caldesmon, desmin, and smooth muscle actin, as well as BCL1, CD10, and CD68. Next generation sequencing showed four pathogenic genomic aberrations involving BIRC3, FANCC, TP53, and TSC1 genes. His work-up was negative for metastatic disease; a wide local excision was performed. Including the reported patient, cutaneous PEComa has been described in 65 individuals: primary benign (N=58), primary malignant (N=5), and metastatic malignant (N=2). Cutaneous PEComa typically presented as a painless, slowly growing nodule of <2 centimeters on the lower extremity of a woman in her fifth decade. The neoplasms consisted of epithelioid cells, spindle cells, or both. The most reliable markers were MiTF (100%), HMB45 (94%), and NKIC3 (94%) for melanocytes and smooth muscle actin (43%) and desmin (40%) for smooth muscle. There has been no reported recurrence of a primary cutaneous benign or malignant PEComa after complete excision. Genomic alterations in malignant PEComas frequently involve TSC1 and TSC2 genes (mTOR activators), as well as TFE3 fusions. In November 2021, the FDA approved nab-sirolimus (mTOR inhibitor) for PEComas.

Multiple skin neoplasms at one site (MUSK IN A NEST): collision tumor consisting of epidermal (macular seborrheic keratosis) and dermal (lichen amyloidosis) components.

A collision tumor is a neoplastic lesion comprised of two or more tumors consisting of distinct cell populations in the concurrent location. Multiple skin neoplasms at one site (MUSK IN A NEST) is a term recently coined to describe two or more cutaneous benign or malignant tumors occurring at the same anatomic site. In retrospective studies, seborrheic keratosis and cutaneous amyloidosis have both individually been documented as a component of a MUSK IN A NEST. This report describes a 42-year-old woman who presented with a pruritic skin condition on her arms and legs of 13 years' duration. Skin biopsy results showed epidermal hyperplasia with hyperkeratosis, hyperpigmentation of the basal layer with mild acanthosis, and evidence of amyloid deposition in the papillary dermis. Based on the clinical presentation and pathology findings, a concurrent diagnosis of macular seborrheic keratosis and lichen amyloidosis was established. A MUSK IN A NEST consisting of a macular seborrheic keratosis and lichen amyloidosis is likely a more common occurrence than implied by the paucity of published cases of this phenomenon.

Acquired giant plantar fibrokeratoma: case report and review.

Acquired digital fibrokeratoma is a benign fibrous tumor usually located on the toes and fingers. A 63-year-old man with an acquired giant plantar fibrokeratoma is described. He presented with an asymptomatic exophytic nodule of ten years duration; there is no history of trauma to the site. It measured 15x10x5mm and was located on the plantar foot proximal to the third toe. Excisional biopsy established the diagnosis of fibrokeratoma. Giant acquired fibrokeratoma,has been described in 16 patients including ours: three women and 13 men. They are located on either the upper extremity (one man) or the lower extremity (15 individuals). Acquired plantar fibrokeratoma is rare. Including our patient, it has been reported in 11 patients: one woman and ten men. The woman was 13 years of age and the men ranged from 15 to 77-years-old. Plantar acquired fibrokeratomas are located on either the plantar aspect of the toes, the sole of the foot, or the heel. An excisional biopsy provided adequate treatment without subsequent recurrence of both giant and plantar fibrokeratomas.

An unusual case of pyogenic granuloma-like Kaposi sarcoma.

Kaposi sarcoma (KS) is not typically included in the differential diagnosis of lesions with clinical characteristics of pyogenic granuloma. However, cases of pyogenic granuloma-like Kaposi sarcoma have been reported in the literature. This variant is extremely rare and possesses clinical and histological findings consistent with both conditions. We report an elderly, immunocompetent man with pyogenic granuloma-like Kaposi sarcoma, which was clinically consistent with a pyogenic granuloma and possessed histological findings consistent with Kaposi sarcoma and pyogenic granuloma.

Terbinafine-induced lichenoid drug eruption: case report and review of terbinafine-associated cutaneous adverse events.

Terbinafine is an antifungal agent used in the treatment of hair, nail, and skin dermatophyte infections. Skin side effects to terbinafine are not common. Lichenoid drug eruption is a medication-related adverse cutaneous event; the lesion morphology and pathology mimic lichen planus. A woman with onychomycosis developed a lichenoid drug eruption one week after starting terbinafine. The features of her dermatosis and the characteristics of two additional men who also experienced terbinafine-induced lichenoid drug eruption are discussed. They were receiving a daily terbinafine dosage of either 125mg or 250mg to treat onychomycosis or tinea cruris. The lichenoid drug eruption presented as diffuse or symmetric lesions within one to two weeks after starting terbinafine treatment. The extremities, chest, abdomen, and/or trunk were common sites. Less frequent locations were the lips, nails, palms, soles, and suprapubic region; lesions did not occur on the oral or genital mucosa. The eruption resolved after discontinuation of the medication (with or without treatment using topical corticosteroids, systemic corticosteroids, or both). In addition, more frequently occurring terbinafine-associated cutaneous adverse events (such as urticaria, erythematous eruptions, pruritus, acute generalized exanthematous pustulosis, subacute cutaneous lupus erythematosus, and papulosquamous conditions) are reviewed.

Case report and review of solitary cutaneous focal mucinosis: a unique primary cutaneous mucinosis unrelated to mucinosis-associated systemic diseases.

Localized deposition of mucin in the upper dermis is referred to as cutaneous focal mucinosis. Patients with this condition either present with a single skin lesion (solitary cutaneous focal mucinosis) or numerous skin lesions (multiple cutaneous focal mucinosis). A man with solitary cutaneous focal mucinosis is described and the features of this condition are reviewed. Solitary cutaneous focal mucinosis has a slight male predominance and typically presents in adults, ranging in age from 29 years to 60 years, as a nodule or papule that is flesh-colored or white and most commonly located on an extremity or the trunk. Microscopic examination shows deposition of mucin in the upper dermis; the overlying epidermis can be normal, atrophic or hyperplastic. The skin lesion is often removed at the time of biopsy. However, recurrence has not been observed when the mucin deposition is present at the edge of the biopsy or excision specimen. Although the pathogenesis of this condition remains to be established, in contrast to individuals with multiple cutaneous focal mucinosis, solitary cutaneous focal mucinosis is a unique primary cutaneous mucinosis unrelated to mucinosis-associated systemic diseases.

Nevus sebaceus with syringocystadenoma papilliferum, prurigo nodularis, apocrine cystadenoma, basaloid follicular proliferation, and sebaceoma: case report and review of nevus sebaceus-associated conditions.

Nevus sebaceus is a benign skin hamartoma of congenital onset that grows during puberty, and in adulthood can develop secondary benign and malignant neoplasms. The most common benign neoplasms occurring in nevus sebaceus are believed to be syringocystadenoma papilliferum, trichilemmoma, and trichoblastoma. A patient with nevus sebaceus developed not only syringocystadenoma papilliferum but also prurigo nodularis within her hamartomatous lesion; multiple biopsies were necessary to establish the diagnoses. Excision of the residual nevus sebaceus also revealed an apocrine cystadenoma, basaloid follicular proliferation, and sebaceoma. Also, it is important to select the appropriate biopsy site and size when evaluating a patient for secondary neoplasms within their nevus sebaceous. Indeed, more than one biopsy may be required if additional diagnoses are suspected.

Histologic and Clinical Changes in Vulvovaginal Tissue After Treatment With a Transcutaneous Temperature-Controlled Radiofrequency Device.

BACKGROUND: Although transcutaneous temperature-controlled radiofrequency (TTCRF) may effectively treat vulvovaginal laxity (VVL), atrophic vaginitis (AV), orgasmic dysfunction (OD), and stress urinary incontinence (SUI), there is a lack of histopathologic evidence to validate its use. OBJECTIVE: Evaluate clinical and histological changes induced by vulvovaginal TTCRF. MATERIALS AND METHODS: This was a prospective, nonrandomized trial. Ten female subjects with mild-to-moderate VVL, with or without AV, OD, and/or SUI underwent 3 TTCRFs at 4-week intervals. Five subjects underwent pre- and post-treatment biopsies of the labia majora and vaginal canal for histology. Assessments were performed at baseline and Days 10, 30, 60, and 120. RESULTS: Investigator-rated VVL improved significantly from baseline to Day 10, with improvement maintained through Day 120 (p = .001 and .001, respectively). Sexual satisfaction improved significantly by Day 60 (p = .001). Improvement in AV reached significance at Day 120 (p = .048). Although OD and SUI improved steadily, the difference in improvement did not reach statistical significance. Histology revealed that post-treatment increases in collagen, elastin, vascularity, and small nerve fibers. CONCLUSION: Transcutaneous temperature-controlled RF resulted in significant improvements in AV, VVL, and sexual satisfaction with milder improvements in OD and SUI. Post-treatment histology demonstrated neocollagenesis, neoelastogenesis, neoangiogenesis, and the first reported finding of TTCRF-related neurogenesis.

Keratoacanthomatous Changes: Unifying the Histologic Spectrum of Actinic Granuloma.

Actinic granuloma (AG) manifests as annular plaques on sun-damaged skin. There remains no universal consensus on the nosology, etiology, or clinicopathologic criteria of AG as a distinct entity. Broadly, AG is characterized by granulomatous inflammation, multinucleated giant cells, elastophagocytosis, and the absence of mucin and necrobiosis. It is not uncommon, however, to encounter overlapping histological features of other granulomas, such as granuloma annulare and necrobiosis lipoidica, confounding the diagnosis of this controversial entity. Herein, we describe 2 cases of AG with features of granuloma annulare and necrobiosis lipoidica, supporting the concept of AG as a histologic spectrum. These 2 cases displayed dilated follicular infundibula and pseudoepitheliomatous hyperplasia analogous to changes in keratoacanthomas. These unique epithelial changes, in tandem with characteristic elastin alterations and clinical findings, are helpful and unifying features that permit accurate diagnosis of this controversial entity.

Pediatric penile porokeratosis: A case report.

We present what we believe to be the second case of pediatric penile porokeratosis and the youngest case reported. A 6-year-old boy presented with a pruritic, verrucous growth at the urethral meatus that recurred after two meatotomies. The diagnosis of porokeratosis was confirmed by biopsy. Porokeratosis should be added to the differential diagnosis of chronic hyperkeratotic penile lesions in children.

Psoriasiform eruptions during Kawasaki disease (KD): A distinct phenotype.

BACKGROUND: A psoriasis-like eruption develops in a subset of patients with Kawasaki disease (KD). OBJECTIVE: We sought to systematically compare KD-associated psoriasiform eruptions with classic psoriasis and the outcomes of KD in children with and without this rash. METHODS: This was a retrospective study of 11 KD cases with a psoriasiform eruption matched 1:2 by age, gender, and ethnicity with psoriasis-only and KD-only controls. Genotyping was performed in 10 cases for a deletion of 2 late cornified envelope (LCE) genes, LCE3C_LCE3B-del, associated with increased risk for pediatric-onset psoriasis. RESULTS: Similar to classic psoriasis, KD-associated eruptions were characterized clinically by well-demarcated, scaly pink plaques and histopathologically by intraepidermal neutrophils, suprabasilar keratin 16 expression, and increased Ki-67 expression. They showed less frequent diaper area involvement, more crust and serous exudate, and an enduring remission (91% vs 23% with confirmed resolution; P < .001). Frequency of LCE3C_LCE3B-del and major KD outcomes were similar between cases and controls. LIMITATIONS: The study was limited by the small number of cases, treatment variation, and availability of skin biopsy specimens. CONCLUSIONS: Although the overall clinical and histopathologic findings were similar to conventional psoriasis, this appears to be a distinct phenotype with significantly greater propensity for remission. No adverse effect on KD outcomes was noted.

Evaluation of the in vivo effects of various laser, light, or ultrasound modalities on human skin treated with a collagen and polymethylmethacrylate microsphere dermal filler product.

BACKGROUND: Bellafill® is a soft tissue dermal filler composed of non-resorbable polymethylmethacrylate (PMMA) microspheres, suspended in a water-based carrier gel composed of 3.5% bovine collagen. It has been approved by the FDA for the correction of nasolabial folds and atrophic facial acne scars. Energy-based therapies are used for facial rejuvenation and treatment of acne scarring. However, little has been published about the effects of energy devices on previously placed PMMA. This prospective, in vivo clinical study evaluated the safety and histopathological effects of a number of different laser, light, and ultrasound treatment modalities on PMMA-collagen filler previously injected into human tissue. METHODS: Following a negative reaction to the bovine collagen skin test, the abdomen of one subject (with planned mini-abdominoplasty) was divided into a grid with 32 treatment sections. Seventeen treatment areas received subdermal injections of PMMA-collagen product (0.1-0.2 cc in each area). The subject was assessed for adverse events at each post-treatment office visit. Eighty days post-injection, 30 treatment sections were treated with laser, light, or ultrasound therapy (16 of the 17 PMMA-collagen treated areas, with two of those areas receiving a combination of therapies, and an additional 14 areas receiving laser therapy alone). One PMMA-collagen treated area was not exposed to any energy devices, and one remaining treatment area received no treatment of any kind, representing an internal control. Sixty days following energy device treatment, the tissue was excised in a planned mini-abdominoplasty procedure and sent for histological examination. RESULTS: The subject experienced no adverse events during the study. No histological changes in PMMA microspheres were observed in any treatment area. An expected lymphohistiocytic response was identified in all areas where PMMA microspheres were present. CONCLUSION: Laser, light, and ultrasound treatments can safely be administered following a PMMA-collagen injection. Lasers Surg. Med. 48:811-819, 2016. © 2016 Wiley Periodicals, Inc.

Atypical Fibroxanthoma in a 13-Year-Old Guatemalan Girl with Xeroderma Pigmentosum.

Xeroderma pigmentosum (XP) is a rare, autosomal recessive disease involving a defect in DNA repair leading to the premature development of numerous aggressive cutaneous malignancies. Although atypical fibroxanthoma (AFX) is a neoplasm typically found in the setting of extensive sun exposure or therapeutic radiation, AFXs are rarely associated with children with XP. We report the case of a 13-year-old Guatemalan girl with the XP type C variant who developed one of the largest AFXs reported on a child's finger.

Use of Oral Polypodium Leucotomos Extract in Chronic Photoinduced Hypersensitivity Dermatitis.

A 52-year-old man with Fitzpatrick type V skin presented for evaluation of a photodistributed eruption of unknown origin. The patient reported a 20-year history of the dermatitis, with worsening severity during the past 6 years. He had required one hospital admission with intravenous methylprednisolone and two extended courses of oral prednisone (starting dose of 60 mg/d). He complained of pruritus and swelling localized to the sun-exposed areas of the forearms, face, and neck, with notable sparing of photoprotected areas of his skin. He denied new medications, and a systemic review of systems was noncontributory.

Ecthyma Gangrenosum-Like Lesions Secondary to Methicillin-Sensitive Staphylococcus aureus in an Immunocompetent Child.

We describe a previously healthy 15-month-old girl who developed ecthyma gangrenosum (EG)-like lesions secondary to methicillin-sensitive Staphylococcus aureus (MSSA). Her systemic symptoms and negative blood cultures suggested MSSA toxin-mediated effects. When toxin-mediated systemic symptoms accompany such lesions, pathogens other than Pseudomonas aeruginosa should be considered.

Lichen Planus Pigmentosus Inversus: A Case Report of a Man Presenting With a Pigmented Lichenoid Axillary Inverse Dermatosis (PLAID).

Lichen planus pigmentosus is an uncommon subtype of lichen planus and lichen planus pigmentosus inversus is a rare variant of lichen planus pigmentosus. Lichen planus pigmentosus inversus typically presents as hyperpigmented patches or plaques, particularly in the intertriginous areas such as the axillae, the groin and inguinal folds, and in the submammary region. In some patients with lichen planus pigmentosus inversus, the condition can present as a pigmented lichenoid axillary inverse dermatosis (PLAID) when the lesions are in the axillae. A 49-year-old Hispanic man who had hyperlipidemia and diabetes mellitus developed lichen planus pigmentosus inversus and presented with a PLAID. Skin biopsies established the diagnosis of lichen planus pigmentosus inversus. The clinical differential diagnosis of lichen planus pigmentosus inversus includes inherited disorders, primary cutaneous dermatoses, acquired dyschromias, and reactions to topical or systemic medications. Friction in intertriginous areas has been related to the development of lichen planus pigmentosus inversus. Factors that can precipitate lichen planus pigmentosus inversus include not only topical exposure to almond oil, amala oil, cold and cosmetic creams, henna, and paraphenyldiamine but also either topical contact or consumption of mustard oil and nickel. Lichen planus pigmentosus inversus can be associated with autoimmune conditions (hypothyroidism), endocrinopathies (diabetes mellitus), and hyperlipidemia. The dyschromia found in patients with lichen planus pigmentosus inversus is frequently refractory to treatment. Initial management includes removal of potential disease triggers such as eliminating tight clothing to stop friction with the adjacent skin. Topical corticosteroids do not result in improvement; however, topical calcineurin inhibitors such as tacrolimus have been reported to be efficacious. In conclusion, inverse lichen planus and lichen planus pigmentosus inversus can present with a PLAID; whereas topical corticosteroids may be helpful to resolve inverse lichen planus lesions, topical tacrolimus may be useful to improve the dyschromia in lichen planus pigmentosus inversus.

Halo Phenomenon in Lobular Capillary Hemangioma: A Case Report of a Pyogenic Granuloma With Surrounding Cutaneous Hypopigmentation and Review of Tumors With Halo Phenomenon.

A halo phenomenon describes a skin neoplasm that is surrounded by a hypopigmented or white halo. Halo lesions have been observed in association with an epithelial neoplasm (seborrheic keratosis), a fibrous lesion (surgical scar), a keratinocyte malignancy (basal cell carcinoma), melanocytic neoplasms, and vascular lesions. Benign lesions (café au lait macules and nevi) and malignant tumors (primary and metastatic melanoma) are melanocytic neoplasms that have developed perilesional halos. Halo nevi are a commonly occurring manifestation of a halo phenomenon; however, perilesional hypopigmented halos have also been observed around nevi in patients following treatment with antineoplastic drugs, acquisition of COVID-19 (infection and vaccine), the occurrence of a visceral tumor (including not only melanoma, but also papillary thyroid carcinoma and neuroendocrine cancer of the lung), surgery (such as the excision of a primary melanoma), and Turner syndrome. A halo phenomenon has also been observed in patients with congenital (capillary malformation-arteriovenous malformation and congenital hemangioma) or acquired (angioma, eruptive pseudoangiomatosis, infantile hemangioma, and lobular capillary hemangioma) vascular lesions. In summary, a halo phenomenon can occur in association with primary lesions of various embryologic derivations. Most commonly, they have been observed in around nevi and vascular tumors. Halo lobular capillary hemangioma can be added to the list of acquired vascular lesions with the potential to develop a halo phenomenon. The preservation of melanocytes with loss of melanin pigment expression in the reported patient suggests the possibility that a post-inflammatory etiology may be responsible for the genesis of her halo lobular capillary hemangioma.

Mobile Subcutaneous Calcinosis Cutis: A Case Report of a Mobile Solitary Subepidermal Calcified Nodule on a Woman's Leg and a Review of Mobile Subcutaneous Tumors.

Calcinosis cutis describes the deposition of calcium in the dermis. A case of a 69-year-old woman with idiopathic calcinosis cutis that presented as a mobile subcutaneous nodule is described. The patient had an asymptomatic, firm, mobile subcutaneous nodule on her right lower leg of at least six months duration. The nodule could be easily moved from one location to another. An incisional biopsy was performed. Microscopic examination of the tissue specimen showed islands of basophilic calcium material in dense sclerotic dermal connective tissue establishing the diagnosis of calcinosis cutis. Mobile solitary calcification is an unusual presentation of idiopathic calcinosis cutis. In addition to idiopathic calcinosis cutis, benign mobile subcutaneous tumors have also been derived from adnexal structures of hair follicles and adipose tissue. Hence, not only idiopathic calcinosis cutis, but also subepidermal calcinosis in the ocular adnexa, proliferating trichilemmal cyst with focal calcification, and mobile encapsulated adipose tissue can present as a mobile subcutaneous nodule. The features of idiopathic calcinosis presenting as a mobile subcutaneous nodule as well as the characteristics of other benign mobile subcutaneous tumors are reviewed.

Tender Nasal Traumatic (TNT) Neuroma: Case Report and Review.

A traumatic neuroma occurs at the injury site of a peripheral nerve; however, albeit rarely, this variant of a neuroma can involve a nerve that has not experienced penetrating trauma. A lower extremity amputation stump is the most common location of a traumatic neuroma. Traumatic neuromas may be symptomatic; tumor-associated pain can be severe and significantly affect the patient's quality of life. Several hypotheses have been postulated for the pathogenesis of neuroma-related pain, including alpha-smooth muscle actin, neural fiber structural changes, nerve growth factor, and/or sensitization of the affected nerve. In addition to prevention, non-surgical treatment (such as chemical interventions, cryotherapy, neuromodulation, pharmacologic agents, and physiotherapy) and surgical interventions (such as direct nerve repair at the time of injury or ligation of the nerve proximal to the neuroma and various potential methods to minimize subsequent irritation of the distal free end of the proximal nerve) have been used to manage neuroma-associated pain. A traumatic neuroma of the nose is rare. Indeed, it has only been described in three individuals: two women (including the Caucasian woman in this report and a Turkish woman) and one man. The benign tumor was extremely painful in both women; however, the man's lesion was non-tender. Prior trauma to the nasal site included either a laceration or elective surgery; however, the reported woman did not experience any penetrating trauma to her nose. The diagnosis was established following an excisional (for the man), incisional (for the Turkish woman), or punch (for the Caucasian woman) biopsy. Follow-up was provided for two of the patients. The man's neuroma had been completely excised, and he never developed tumor-associated tenderness. However, the pain persisted after the biopsy healed for the reported woman whose neuroma was not entirely removed. The explosive and markedly severe character of the reported patient's lesion-related tenderness prompted us to propose an acronym for this uncommon yet exquisitely painful variant of a neuroma: tender nasal traumatic (TNT) neuroma.