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BACKGROUND: Categorization of biopsy specimens into inflammatory reaction patterns is central to dermatopathologic assessment. Mixed inflammatory patterns are poorly characterized and may represent clinicopathologic challenges. The purpose of this study was to identify clinical and histopathologic findings associated with the mixed spongiotic-interface dermatitis (SID) histopathologic pattern.
METHODS: Fifty-one institutional biopsy specimens of SID were identified over a 2-year period by retrospective natural language search. Histopathologic and clinical features were identified.
RESULTS: The most common histopathologic features associated with SID were mild spongiosis (51%), focal vacuolar interface change (72%), lymphocytic exocytosis (92%), and superficial-dermal lymphocytic infiltrate (94%) with variable eosinophils (61%). Clinically, 80% of subjects presented with a symmetric morbilliform eruption. Polypharmacy (94%), immunosuppression (47%), and history of malignancy (47%) were common. The most common diagnoses were drug reaction (37%), possible drug reaction (12%), and viral exanthem (12%). Drug reaction with eosinophilia and systemic symptoms represented 25% of all confirmed cutaneous adverse drug reactions (CADR). Average time from drug initiation to symptom initiation was 20 days (SD: 22.3, range: 0-90); median disease duration was 25.5 days. Spongiotic vesicles and Langerhans cells were less common in patients with a strong clinicopathologic diagnosis of drug reaction compared to non-drug eruptions (p = 0.04).
CONCLUSIONS: The mixed SID pattern is commonly encountered in CADR but may represent a more subacute course, implying consideration for inciting medication(s) started before the typical 7- to 14-day window.

Immune checkpoint inhibitors (ICIs), a class of anticancer agents that upregulate T-cell response to tumor cells, are associated with immune-related adverse events (irAEs), and the skin is one of the most commonly affected organs. We report the first two cases of a unique ICI-induced clinicopathological entity. A psoriasiform-appearing eruption with psoriasiform, spongiotic, and lichenoid dermatitis pattern on histopathology. A 73-year-old male with stage IV melanoma treated with nivolumab and a 63-year-old female with stage IV colorectal cancer treated with pembrolizumab and TAK-981 separately presented to our clinic with a psoriasiform rash. In both patients, punch biopsy revealed an unusual combination of psoriasiform, spongiotic, and lichenoid dermatitis. Treatment with apremilast in the first patient yielded some improvement, while treatment with ixekizumab in the second patient yielded a complete resolution of the eruption. Our cases add to the growing body of reported immune toxicities related to ICI use and illustrate the utility of targeted immune suppression of pathways in disease phenotype to allow for ICI continuation and optimization of cancer treatment.

BACKGROUND: Cutaneous adverse events are common with programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors. However, the nature of the specific cutaneous adverse event of dermatitis has not been investigated across various PD-1/PD-L1 inhibitors. Oncologic outcomes potentially associated with dermatitis are not well characterized.
OBJECTIVE: To assess the nature of dermatitis after exposure to a PD-1/PD-L1 inhibitor and oncologic outcomes associated with dermatitis.
METHODS: Retrospective, matched, case-control study conducted at a single academic center.
RESULTS: The most common histologic patterns were lichenoid dermatitis (50%) and spongiotic dermatitis (40%). The overall tumor response rate was 65.0% for the case patients and 17.0% for the controls (P = .0007) (odds ratio, 7.3; 95% confidence interval, 2.3-23.1). The progression-free survival and overall survival times were significantly longer for the case patients than for the controls by Kaplan-Meier analysis (P < .0001 and .0203, respectively).
CONCLUSIONS: The retrospective design and relatively small sample size precluded matching for all cancer types.
CONCLUSIONS: Lichenoid and spongiotic dermatitis associated with PD-1/PD-L1 inhibitors could be a sign of robust immune response and improved oncologic outcomes. The value of PD-1/PD-L1-related dermatitis in predicting cancer outcomes awaits investigation through prospective multicenter studies for specific cancer types.

Owing to the wide variety and complexity of inflammatory skin diseases, inflammatory dermatopathology can be a challenging topic for dermatopathologists and general surgical pathologists alike. Following a basic tissue reaction pattern approach, this article reviews the most common and important entities of each pattern, with emphasis on differential diagnosis, diagnostic pitfalls, and appropriate workup when indicated. A few dermatologic emergencies are also discussed.

OBJECTIVE: Localized juvenile spongiotic gingival hyperplasia (LJSGH) is a painless gingival swelling that histologically exhibits hyperplasia of the non-keratinized stratified squamous epithelium, intercellular edema and spongiosis of the spinus layer, and exocytosis of inflammatory cells. LJSGH pathogenesis remains to be elucidated, while a possible origin from the gingival sulcus epithelium is nowadays proposed.
METHODS: We report two cases of LJSGH with immunohistochemical evaluation of cytokeratins (CKs) 18 and 19.
RESULTS: Both cases concerned 12-year-old boys, who presented with a well-circumscribed bright red pedunculated papillary swelling on the marginal gingiva of the left maxillary lateral incisor. With the provisional diagnosis of LJSGH, the lesions were excised under local anesthesia and histological examination supported the final diagnosis of LJSGH. In both cases, the lesional epithelium showed intense and mild positivity for CK19 and CK18, respectively, while the adjacent normal gingival epithelium expressed CK19, but not CK18, only in the basal cell layer. The postoperative course was uneventful in both patients and no recurrence has been reported.
CONCLUSIONS: LJSGH is a recently introduced entity that is worth attention in the clinical pediatric dentistry. Clinical and histological examination is required for the final diagnosis, while immunohistochemistry has shed light to LJSGH pathogenesis.

BACKGROUND: Tumor necrosis factor-α (TNF-α) inhibitors, such as infliximab, adalimumab, and certolizumab pegol are effective agents in the treatment of inflammatory bowel disease. Some individuals undergoing anti-TNF-α therapy for Crohn\'s disease or ulcerative colitis develop psoriasiform lesions. This is a paradoxical finding, as classical psoriasis is known to respond to these agents.
OBJECTIVE: The clinical features of anti-TNF-α-induced psoriatic dermatitis are described.
METHODS: A 60-year-old man with Crohn\'s disease treated with infliximab, who developed anti-TNF-α-induced psoriasiform dermatitis, is described.
RESULTS: The man developed erythematous skin lesions in the bilateral axillae two years after beginning infliximab treatment for Crohn\'s disease. Biopsy revealed psoriasiform dermatitis, consistent with a diagnosis of anti-TNF-α-induced psoriasiform dermatitis. He was treated with clobetasol 0.05% ointment twice daily for two weeks and had significant improvement. Subsequently, he used the corticosteroid ointment two days per week and calcipotriene 0.005% ointment twice daily for five days per week to achieve and maintain clear skin.
CONCLUSIONS: Anti-TNF-α-induced psoriasiform dermatitis is an infrequent complication of infliximab therapy. However, the condition may require discontinuation of the anti-TNF-α agent. Anti-TNF-α-induced psoriasiform dermatitis should be considered in the differential diagnosis when evaluating a new erythematous skin condition in an individual with a history of inflammatory bowel disease who is being treated with a TNF-α inhibitor.

Linear dermatoses are fascinating entities that likely reflect embryologically derived cutaneous mosaicism, even when they occur after childhood. Adult blaschkitis is a rare, relapsing inflammatory dermatitis that most often presents in middle age. It presents clinically as a pruritic eruption of linear papules, vesicles and plaques, and is most commonly found to have features of spongiotic dermatitis on pathology. However, the clinical and histopathologic presentation of lichen striatus in adults may be similar to those of adult blaschkitis. A case in which \'blaschkitis\' was suspected clinically is presented, in which the biopsy showed non-characteristic microscopic features resembling erythema multiforme--a finding rarely reported in the literature to date. We present this case and a brief review of the most commonly acquired linear eruptions following Blaschko\'s lines with the goal of expanding the histopathologic findings that may be encountered in adult blaschkitis. Moreover, the clinical and histopathologic overlap between the entities of blaschkitis and lichen striatus is explored, acknowledging that these entities may exist on a clinicopathologic spectrum. In the diagnosis of linear eruptions, clinicopathologic correlation is important for arriving at an accurate final diagnosis.

BACKGROUND: Localized juvenile spongiotic gingival hyperplasia (LJSGH) is a distinct type of gingival hyperplastic lesion with specific clinicopathologic features. Evaluation of the morphological characteristics of LJSGH indicates the potential role of human papillomavirus (HPV) infection as an underlying etiopathogenetic mechanism.
METHODS: All cases of LJSGH from 2008 to present were retrieved. Clinical and demographic data were collected. HPV status was investigated by p16INK4A immunohistochemistry and HPV-Polymerase chain reaction (PCR).
RESULTS: Twenty-one cases of LJSGH were identified, 14 (66.7%) affecting males and seven (33.3%) females (M:F = 2:1, age range: 8-36, mean: 13 years). All lesions were well-demarcated, exophytic, erythematous, and hemorrhagic with granular or slightly papillary surface. Preponderance for the maxillary gingiva (19, 90.5%) was observed. Two (9.5%) patients presented with recurrence 20 and 21 months after excision (mean follow-up: 18.7 months). Histopathologically, all LJSGH lesions featured epithelial hyperplasia with intense neutrophilic exocytosis and spongiosis. All cases demonstrated positivity for p16INK4A with the majority of specimens (47.6%) intensely decorated in >50% of the overlying epithelium with focal immunostaining observed in 47.6% and diffuse in 52.4%. Thirteen cases (61.9%) were negative for HPV DNA by PCR, while two (9.5%) were suspicious for the presence of low levels of HPV DNA but definitive genotyping was not possible. One case (4.8%) displayed positivity for HPV-31. The remaining five cases failed the PCR reaction.
CONCLUSIONS: Human papillomavirus does not participate in the pathogenesis of LJSGH. P16INK4A expression in the absence of detectable HPV DNA can likely be attributed to the intense inflammation associated with LJSGH.