Banff 2022 Vascularized Composite Allotransplantation Meeting Report: Diagnostic criteria for vascular changes.

As more data become available, the Banff 2007 working classification of skin-containing vascularized composite allograft (VCA) pathology is expected to evolve and develop. This report represents the Banff VCA Working Group's consensus on the first revision of the 2007 scoring system. Prior to the 2022 Banff-CanXadian Society of Transplantation Joint Meeting, 83 clinicians and/or researchers were invited to a virtual meeting to discuss whether the 2007 Banff VCA system called for a revision. Unanimously, it was determined that the vascular changes were to be included in the first revision. Subsequently, 2 international online surveys, each followed by virtual discussions, were launched. The goals were (1) to identify which changes define severe rejection, (2) to grade their importance in the evaluation of severe rejection, and (3) to identify emerging criteria to diagnose rejection. A final hybrid (in-person and virtual) discussion at the Banff/Canadian Society of Transplantation Joint Meeting finalized the terminology, the definition, a scoring system, and a reporting system of the vascular changes. This proposal represents an international consensus on this topic and establishes the first revision of the Banff 2007 working classification of skin-containing vascularized composite allograft pathology.

Bilateral eccrine angiomatous hamartomas of the proximal interphalangeal joints.

Eccrine angiomatous hamartoma is an uncommon, benign clinical entity constituting a nodular proliferation of eccrine glands and vascular structures localized to the dermis that typically present as unilateral, flesh-colored, erythematous, or violaceous papules on the extremities. These hamartomas may be associated with pain, hyperhidrosis, joint deformity, or functional impairment depending on the severity of the disease process. We present a case of bilaterally symmetric, asymptomatic eccrine angiomatous hamartomas involving all proximal interphalangeal joints of both hands. To date, there are only four prior cases of bilaterally symmetric eccrine angiomatous hamartomas reported in the literature, suggesting that the distribution experienced by our patient may represent a previously undescribed syndrome.

Dissecting the immune landscape of tumor draining lymph nodes in melanoma with high-plex spatially resolved protein detection.

BACKGROUND: In melanoma patients, microscopic tumor in the sentinel lymph-node biopsy (SLN) increases the risk of distant metastases, but the transition from tumor in the SLN to metastatic disease remains poorly understood. METHODS: Fluorescent staining for CD3, CD20, CD11c, and DNA was performed on SLN tissue and matching primary tumors. Regions of interest (ROI) were then chosen geometrically (e.g., tumor) or by fluorescent cell subset markers (e.g., CD11c). Each ROI was further analyzed using NanoString Digital Spatial Profiling high-resolution multiplex profiling. Digital counts for 59-panel immune-related proteins were collected and normalized to account for system variation and ROI area. RESULTS: Tumor regions of SLNs had variable infiltration of CD3 cells among patients. The patient with overall survival (OS) > 8 years had the most CD11c- and CD3-expressing cells infiltrating the SLN tumor region. All patients had CD11c (dendritic cell, DC) infiltration into the SLN tumor region. Selecting ROI by specific cell subtype, we compared protein expression of CD11c cells between tumor and non-tumor/normal tissue SLN regions. Known markers of DC activation such as CD86, HLA-DR, and OX40L were lowest on CD11c cells within SLN tumor for the patient with OS < 1 year and highest on the patient with OS > 8 years. CONCLUSION: We demonstrate the feasibility of profiling the protein expression of CD11c cells within the SLN tumor. Identifying early regulators of melanoma control when the disease is microscopically detected in the SLN is beneficial and requires follow-up studies in a larger cohort of patients.

Vascularized composite allotransplants as a mechanistic model for allograft rejection - an experimental study.

Vascularized composite allotransplants (VCAs) seem to have several unique features of clinical and experimental importance, including uniquely definable lymphatic drainage that can be easily accessed at the level of ipsilateral regional node beds. Thus, VCA offers a unique opportunity to assess the relative contribution of peripheral and secondary lymphoid tissue to the process of rejection. We transplanted hind limb grafts from C3H donors to six different groups of C57BL/6 recipients: Spleen+ Map3k14-/- ; Spleen- Map3k14-/- ; Spleen+ Node- Map3k14-/- ; and Spleen- Node- Map3k14-/- . As positive controls, we used Map3k14+/- with or without spleen. Map3k14+/- mice demonstrated an average graft survival of 9.6 and 9.2 days for Spleen- and Spleen+ Map3k14+/- , respectively. Rejection in the Map3k14-/- group was considerably delayed (28.4 days, P = 0.002) in all recipients. The Spleen- Map3k14-/- mice rejected their hind limb allografts in an even more delayed fashion compared to Spleen+ Map3k14-/- (54.4 days, P = 0.02). Histological analysis of skin showed that acute rejection in both Map3k14+/- mice groups was graded as Banff III or Banff IV. In the Map3k14-/- groups, rejection was graded as Banff III. We demonstrated that in the absence of lymph nodes, grafts reject in a delayed fashion. Also, splenectomy in alymphoplastic mice further extends graft survival, but does not eliminate rejection all together.

Histopathology after lidocaine/prilocaine cream administration for vulvar biopsy.

BACKGROUND: Case series have described disruptive histopathologic changes following lidocaine/prilocaine cream anesthetic for biopsies. METHODS: A study of histopathologic changes was performed following a randomized trial comparing topical lidocaine/prilocaine cream to 1% lidocaine injection anesthesia for vulvar biopsy. Histopathology was reviewed by two independent dermatopathologists blinded to the type of anesthetic. Specimens were scored on six histopathologic criteria described in the literature. Individual scores for each histopathologic feature and the total score across features were compared between the two groups using marginal models with generalized estimating equations. RESULTS: Of 37 specimens reviewed, 19 were randomized to lidocaine/prilocaine cream and 18 to 1% lidocaine. Subjects exposed to lidocaine/prilocaine had the following odds of histopathologic changes, relative to lidocaine-exposed subjects: acantholysis (odds ratio 2.48; 95% confidence intervals [CI] 0.51, 12.06), clefting (2.42; 0.64, 9.14), pallor/necrosis (1.13; 0.28, 4.50), spongiosis (0.71; 0.18, 2.85), and papillary dermal edema (1.17; 0.41, 3.29). Total scores were not significantly different between treatment arms (risk ratio 0.98; 0.71, 1.35). CONCLUSION: This histopathologic analysis of a randomized trial between lidocaine/prilocaine cream and injected lidocaine as anesthesia for vulvar biopsy shows the absence of significant disruptive histopathologic features secondary to the type of anesthetic. Additional studies in different clinical contexts are warranted.

Resolution of Pembrolizumab-Associated Steroid-Refractory Lichenoid Dermatitis with Cyclosporine.

Checkpoint inhibitors such as pembrolizumab, an anti-PD-1 monoclonal antibody, are a promising new category of oncological therapeutics, associated with a higher risk of immune-related adverse events including dermatological, autoimmune and endocrine sequelae. Here, we present a case of a woman 76 years of age with stage IV lung adenocarcinoma who developed a severe and steroid-refractory lichenoid dermatitis associated with pruritus on pembrolizumab. This eruption resolved completely with a short course of oral cyclosporine. Cyclosporine is a promising and effective treatment option for checkpoint inhibitor-related severe cutaneous eruptions.

Label-Free Imaging of Female Genital Tract Melanocytic Lesions With Pump-Probe Microscopy: A Promising Diagnostic Tool.

OBJECTIVES: Melanomas of the female genital tract present a unique clinical challenge. Not only are these lesions in an anatomically sensitive area, but also they tend to be multifocal and have high recurrence rates. Furthermore, several benign melanocytic proliferations resemble early-stage melanoma clinically and/or histopathologically. Thus, there is a significant need for additional tools that can help correctly diagnose and stage these lesions. Here, we quantitatively and nondestructively analyze the chemical composition of melanin in excised pigmented lesions of the female genital tract using pump-probe microscopy, a high-resolution optical imaging technique that is sensitive to many biochemical properties of melanin. MATERIALS AND METHODS: Thirty-one thin (~5 µm) tissue sections previously excised from female genital tract melanocytic lesions were imaged with pump-probe microscopy and analyzed. RESULTS: We find significant quantitative differences in melanin type and structure between melanoma and nonmalignant melanocytic proliferations. Our analysis also suggests a link between the molecular signatures of melanins and lesion-specific genetic mutations. Finally, significant differences are found between metastatic and nonmetastatic melanomas. The limitations of this work include the fact that molecular information is restricted to melanin pigment and the sample size is relatively small. CONCLUSIONS: Pump-probe microscopy provides unique information regarding the biochemical composition of genital tract melanocytic lesions, which can be used to improve the diagnosis and staging of vulvar melanomas.

Melanocytic tumors with intraepidermal melanophages: a report of five cases with review of 231 archived cutaneous melanocytic tumors.

Dermal melanophages are frequently encountered in both benign melanocytic nevi and malignant melanoma. In contrast, intraepidermal melanophages (IEM) are under-recognized in melanocytic lesions and their biologic significance is not understood. Herein, we report the clinical and histopathologic features of five melanocytic lesions featuring IEM encountered prospectively in our dermatopathology practice at the University of Chicago. Two hundred and thirty-one (231) archived skin primary melanocytic proliferations were also investigated retrospectively in a de-identified, archival teaching set collection. Nineteen of 231 of the archived cases were positive for IEM. Among the total 24 IEM-positive cases (5 prospective and 19 archived cases), 13 were categorized as Spitz nevi (p < 0.0001) and 3 as atypical Spitz tumors (p = 0.0152). Fourteen of 24 cases with IEM also exhibited intracorneal melanocytes (p < 0.0001). IEM are evidently not rare, especially in spitzoid melanocytic neoplasms. IEM in our series were significantly correlated with intracorneal melanocytosis, possibly indicating an association between IEM and suprabasal melanocytosis and/or transepidermal elimination of melanocytes.

Evolution of terminology for human-papillomavirus-infection-related vulvar squamous intraepithelial lesions.

OBJECTIVE: The aim of this study was to review the nearly 100-year evolution of terminology applicable to oncogenic human papillomavirus (HPV)-related vulvar intraepithelial squamous lesions and present current consensus terminology. METHODS: An extensive literature search of the English language was performed, which included articles that reviewed French and German publications, from 1922 to 2012. The database search was assisted by representatives of the American Society for Colposcopy and the College of American Pathologists as part of a comprehensive study and consensus effort to achieve unified terminology among gynecologists, dermatologists, pathologists, and other related experts to develop for reporting female and male lower genital and anal HPV related squamous lesions. This was done by the committee referred to as the "LAST" Committee. Some of the results and conclusions have been previously presented and published. This presentation is specifically related to vulvar squamous intraepithelial lesion (SIL)/vulvar intraepithelial neoplasia terminology. RESULTS: This work will review past terminology related to HPV-related vulvar SIL, beginning in 1922. The most current terminology will be presented as proposed by the LAST Committee and considered by the World Health Organization this year in accord with the US-Canadian Academy of Pathology. CONCLUSIONS: A consensus of terminology for HPV-related vulvar SIL has been sought for some time, and currently, some consensus has been achieved. The term "squamous intraepithelial lesion" is favored over "intraepithelial neoplasia." A 2-tier classification, of "high grade (HSIL)" or "low grade (LSIL)," is favored over a 3- or 4-tier classification. The application of this terminology will be discussed.

In vivo analysis of burns in a mouse model using spectroscopic optical coherence tomography.

Spectroscopic analysis of biological tissues can provide insight into changes in structure and function due to disease or injury. Depth-resolved spectroscopic measurements can be implemented for tissue imaging using optical coherence tomography (OCT). Here, spectroscopic OCT is applied to in vivo measurement of burn injury in a mouse model. Data processing and analysis methods are compared for their accuracy. Overall accuracy in classifying burned tissue was found to be as high as 91%, producing an area under the curve of a receiver operating characteristic curve of 0.97. The origins of the spectral changes are identified by correlation with histopathology.

Oncogenic mutations in melanomas and benign melanocytic nevi of the female genital tract.

BACKGROUND: The genetic heterogeneity of melanomas and melanocytic nevi of the female genital tract is poorly understood. OBJECTIVE: We aim to characterize the frequency of mutations of the following genes: BRAF, NRAS, KIT, GNA11, and GNAQ in female genital tract melanomas. We also characterize the frequency of BRAF mutations in female genital tract melanomas compared with melanocytic nevi. METHODS: Mutational screening was performed on the following female genital tract melanocytic neoplasms: 25 melanomas, 7 benign melanocytic nevi, and 4 atypical melanocytic nevi. RESULTS: Of the 25 female genital tract melanoma specimens queried, KIT mutations were detected in 4 (16.0%), NRAS mutations in 4 (16.0%), and BRAF mutations in 2 (8.0%) samples. Two of the tumors with KIT mutations harbored double mutations in the same exon. No GNAQ or GNA11 mutations were identified among 11 melanomas screened. BRAF V600E mutations were detected in 7 of 7 benign melanocytic genital nevi (100%) and 3 of 4 atypical genital nevi (75%). LIMITATIONS: Our study is limited by the small sample size of this rare subset of melanomas. CONCLUSION: KIT, NRAS, and BRAF mutations are found in a subset of female genital tract melanomas. Screening for oncogenic mutations is important for developing and applying clinical therapies for melanomas of the female genital tract.

The role of osteopontin and osteopontin aptamer (OPN-R3) in fibroblast activity.

BACKGROUND: Scarring is believed to be caused by both persistent inflammation and overexuberant fibroblast activation. Osteopontin (OPN) is a cytokine that promotes cell activation. The absence of OPN in vivo reduces dermal scarring. This suggests that OPN is involved in scar formation; however, how OPN exerts these pro-scarring effects is unknown. RNA aptamers are short RNA molecules that bind target proteins with high affinity. The aptamer OPN-R3 (R3) blocks OPN signaling. The role of R3 in preventing dermal fibrosis is unknown. METHODS: Fibroblast migration was analyzed with the use of Boyden Chambers and HEMA-3 staining. Inverted confocal microscopy was used to assess fibroblast focal adhesion length. Adhesion was measured by incubating fluorescently stained fibroblasts on OPN coated 96-well plates. CellTiter 96 AQueous non-radioactive cell proliferation assay was utilized to investigate the proliferative activity of fibroblasts. Free floating collagen lattices were utilized to assess fibroblast contractility. RESULTS: Human dermal fibroblasts migrated significantly in response to OPN. OPN did not induce a significant increase in focal adhesion length compared with controls. Adhesion studies demonstrated that OPN increased fibroblast adhesion. Proliferation assays indicate that OPN increased fibroblast growth. OPN increased fibroblast contractility of collagen lattices. The addition of R3 significantly inhibited OPN-induced activity. CONCLUSION: OPN is associated with scar and exerts pro-scarring effects by increasing cellular migration, adhesion, proliferation, and contractility of human dermal fibroblasts. R3 prevents OPN mediated activity. OPN may be useful for promoting closure of non-healing wounds and the OPN specific aptamer, R3, may be useful for preventing fibrosis.

Multimodality analysis confers a prognostic benefit of a T-cell infiltrated tumor microenvironment and peripheral immune status in patients with melanoma.

BACKGROUND: We previously reported results from a phase 1 study testing intratumoral recombinant poliovirus, lerapolturev, in 12 melanoma patients. All 12 patients received anti-PD-1 systemic therapy before lerapolturev, and 11 of these 12 patients also received anti-PD-1 after lerapolturev. In preclinical models lerapolturev induces intratumoral innate inflammation that engages antitumor T cells. In the current study, prelerapolturev and postlerapolturev tumor biopsies and blood were evaluated for biomarkers of response. METHODS: The following analyses were performed on tumor tissue (n=11): (1) flow cytometric assessment of immune cell density, (2) NanoString Digital Spatial profiling of protein and the transcriptome, and (3) bulk RNA sequencing. Immune cell phenotypes and responsiveness to in vitro stimulation, including in vitro lerapolturev challenge, were measured in peripheral blood (n=12). RESULTS: Three patients who received anti-PD-1 therapy within 30 days of lerapolturev have a current median progression-free survival (PFS) of 2.3 years and had higher CD8+T cell infiltrates in prelerapolturev tumor biopsies relative to that of 7 patients with median PFS of 1.6 months and lower CD8+T cell infiltrates in prelerapolturev tumor biopsies. In peripheral blood, four patients with PFS 2.3 years (including three that received anti-PD-1 therapy within 30 days before lerapolturev and had higher pretreatment tumor CD8+T cell infiltrates) had significantly higher effector memory (CD8+, CCR7-, CD45RA-) but lower CD8+PD-1+ and CD4+PD-1+ cells compared with eight patients with median PFS 1.6 months. In addition, pretreatment blood from the four patients with median PFS 2.3 years had more potent antiviral responses to in vitro lerapolturev challenge compared with eight patients with median PFS 1.6 months. CONCLUSION: An inflamed pretreatment tumor microenvironment, possibly induced by prior anti-PD-1 therapy and a proficient peripheral blood pretreatment innate immune response (antiviral/interferon signaling) to lerapolturev was associated with long term PFS after intratumoral lerapolturev in a small cohort of patients. These findings imply a link between intratumoral T cell inflammation and peripheral immune function. TRIAL REGISTRATION NUMBER: NCT03712358.

Temporal spatial expression and function of non-muscle myosin II isoforms IIA and IIB in scar remodeling.

Scar contracture is believed to be caused by the cell contractility during the remodeling phase of wound healing. Cell contractility is mediated by non-muscle myosin II (NMMII) and actin, but the temporal-spatial expression profile of NMMII isoforms A and B (IIA and IIB) during the remodeling phase and the role of NMMII in scar fibroblast tissue remodeling are unknown. Human scar tissue immunostained for IIA and IIB showed that both isoforms were highly expressed in scar tissue throughout the remodeling phase of repair and expression levels returned to normal after the remodeling phase. Human scar tissue immunostained for ß-, γ- and α-smooth muscle actin showed that all isoforms were consistently expressed throughout the remodeling phase of repair. The ß- and γ-smooth muscle actin were widely expressed throughout the dermis, but α-smooth muscle actin was only locally expressed within the dermis. In vitro, fibroblasts explanted from scar tissue were shown to express more IIA than fibroblasts explanted from normal tissue and scar fibroblasts contracted collagen lattices to a greater extent than normal fibroblasts. Blebbistatin was used to demonstrate the function of NMMII in collagen lattice contraction. In normal tissue, fibroblasts are stress-shielded from external tensile stress by the extracellular matrix. After dermal injury and during remodeling, fibroblasts are exposed to a matrix of increased stiffness. The effect of matrix stiffness on IIA and IIB expression was examined. IIA expression was greater in fibroblasts cultured in collagen lattices with increasing stiffness, and in fibroblasts cultured on glass slides compared with polyacrylamide gels with stiffness of 1 kPa. In conclusion, NMMII and actin isoform expression changes coordinately with the remodeling phase of repair, and NMMII is increased as matrix stiffness increases. As NMMII expression increases, so does the fibroblast contractility.

Validation of a Novel Rodent Model to Test Anti-scarring Therapeutics.

UNLABELLED: Scar contracture is a debilitating disease that affects many people worldwide. There are currently no effective preventative medi- cal treatments. A pivotal step to attaining the goal of developing a treatment is the testing of anti-scarring agents in preclinical hierarchi- cal animal models of human scarring. METHODS: A 2-cm x 2-cm, full- thickness, excisional wound was created in the rats' mid-scapular area. Three experiments were performed. The first experiment determined the optimal dressing in wound contraction. The second experiment de- veloped upon the results of the first experiment, and determined how anatomic site of osmotic pump implantation affected wound healing. The third experiment determined how the size of osmotic pump affect- ed wound healing. Wound healing parameters including rate of wound contraction, systemic and local toxicity, proliferation, collagen archi- tecture, and collagen production were assessed. RESULTS: The results of the present study showed that covering the wound with TegadermTM (3M Health Care, St. Paul, MN) alone had the most linear wound con- traction rate with the smallest standard error of the mean. Implanta- tion of all osmotic pump sizes, when implanted intraperitoneally, was tolerated and did not interfere with wound healing. In contrast, sub- cutaneous implanted pumps caused significant discomfort in the rats. CONCLUSION: Implantation of an osmotic pump intraperitoneal in the rat excisional wound model, where the wound is covered with Tegaderm, provides for a reproducible, accurate, preclinical animal model to study anti-scar contracture treatments. .

Phase I trial of intratumoral PVSRIPO in patients with unresectable, treatment-refractory melanoma.

BACKGROUND: While programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) antagonists have improved the prognosis for many patients with melanoma, around 60% fail therapy. PVSRIPO is a non-neurovirulent rhinovirus:poliovirus chimera that facilitates an antitumor immune response following cell entry via the poliovirus receptor CD155, which is expressed on tumor and antigen-presenting cells. Preclinical studies show that oncolytic virus plus anti-PD-1 therapy leads to a greater antitumor response than either agent alone, warranting clinical investigation. METHODS: An open-label phase I trial of intratumoral PVSRIPO in patients with unresectable melanoma (American Joint Committee on Cancer V.7 stage IIIB, IIIC, or IV) was performed. Eligible patients had disease progression on anti-PD-1 and V-raf murine sarcoma viral oncogene homolog B (BRAF)/mitogen activated protein kinase kinase (MEK) inhibitors (if BRAF mutant). The primary objective was to characterize the safety and tolerability of PVSRIPO. Twelve patients in four cohorts received a total of 1, 2 or 3 injections of PVSRIPO monotherapy, with 21 days between injections. RESULTS: PVSRIPO injections were well tolerated with no serious adverse events (SAEs) or dose-limiting toxicities (DLTs) reported. All adverse events (AEs) were grade (G) 1 or G2 (G1 pruritus most common at 58%); all but two PVSRIPO-treatment related AEs were localized to the injected or adjacent lesions (n=1 G1 hot flash, n=1 G1 fatigue). Four out of 12 patients (33%) achieved an objective response per immune-related response criteria (two observations, 4 weeks apart), including 4/6 (67%) who received three injections. In the four patients with in-transit disease, a pathological complete response (pCR) was observed in two (50%) patients. Following study completion, 11/12 patients (92%) reinitiated immune checkpoint inhibitor-based therapy, and 6/12 patients (50%) remained without progression at a median follow-up time of 18 months. CONCLUSION: Intratumoral PVSRIPO was well tolerated. Despite the limited number of PVSRIPO treatments relative to the overall lesion burden (67% patients>5 lesions), intratumoral PVSRIPO showed promising antitumor activity, with pCR in injected as well as non-injected lesions in select patients. TRIAL REGISTRATION NUMBER: NCT03712358.

Paget disease of the vulva: a histologic study of 56 cases correlating pathologic features and disease course.

The Duke experience with 56 vulvar Paget disease patients was analyzed emphasizing pathologic features and controversial issues. Nearly all patients were Caucasian, and their mean age was 69 years. The average length of follow-up was 5.6 years. For each case, the following histologic features were evaluated and their association with disease course was examined: pseudo-invasion, adnexal involvement, signet-ring cells, cytologic atypia, glands formation, epidermal acantholysis, parakeratosis, hyperkeratosis, and chronic inflammation. The recurrence rate after surgical management was 32%, with epidermal acantholysis being the only statistically significant risk factor. Stromal invasion occurred in 10 patients (18%), and was not a statistically significant adverse prognostic indicator, although the single patient who died of the disease had the deepest stromal invasion. Recurrence was more common after resections with positive surgical margins, but this correlation was not statistically significant. Intraoperative frozen section analysis of the margins did not reduce recurrence rate, nor was it useful in attaining permanent free margins. The Paget cells were consistently reactive with cytokeratin-7 and carcinoembryonic antigen and unreactive with S-100 protein, HMB-45, and Mart-1. In addition, the tumor cells were usually positive for mucin stains. This profile helps distinguish vulvar Paget disease from its mimics, Pagetoid squamous cell carcinoma and malignant melanoma.

Cutaneous metastatic cholangiocarcinoma: a report of three cases and review of the literature.

Cutaneous metastasis from cholangiocarcinoma is an extremely rare event. Herein, we present three cases with review of the literature. Case 1 is that of a young female with scalp metastasis. Cases 2 and 3 involve cutaneous metastasis to the sites of prior biliary drains, one occurring in a young female with a history of multiple biliary surgeries and one in a male with a history of sclerosing cholangitis. Review of the literature shows that the presentation of cutaneous metastases from cholangiocarcinoma can vary in terms of anatomic location and clinical features. The pathological and immunohistochemical profile of metastatic cholangiocarcinoma can be non-specific, and accurate diagnosis relies in part on clinical correlation. In summary, metastatic disease should always be included in the differential diagnosis of cutaneous lesions in patients with known malignancy.

The cutaneous manifestations of atypical complete DiGeorge syndrome: a histopathologic and immunohistochemical study.

DiGeorge syndrome is a congenital anomaly with a constellation of findings that includes thymic hypoplasia. Only a small subset of patients with DiGeorge syndrome has complete athymia, classified as complete DiGeorge anomaly; one third of these patients show an eczematous dermatitis, oligoclonal T-cells and lymphadenopathy, known as atypical complete DiGeorge anomaly. Six biopsies from six patients with the distinctive clinical phenotype of atypical complete DiGeorge anomaly were studied. Every biopsy showed exocytosis (100%), parakeratosis, often confluent and spongiosis (100%). Neutrophilic abscesses (50%), dyskeratosis (67%) and satellite cell necrosis (50%) were seen. Perieccrine and perivascular inflammation were seen in half of the cases. Eosinophils were identified (83%); most commonly in both the epidermis and dermis. All of lymphocytes were CD3 positive. Most (83%) of cases contained T-cell intracellular antigen 1 (TIA-1) positive cells. Special testing of the selected patients using spectratyping identified oligoclonal T-cell populations. The presence of dyskeratotic keratinocytes, satellite cell necrosis and parakeratotic scale with neutrophils characterizes the cutaneous rash seen in this subset of complete DiGeorge syndrome patients. Such skin lesions from patients with DiGeorge anomaly should alert the pathologist to the potential diagnosis of atypical complete DiGeorge anomaly. The pathophysiologic role of the oligoclonal T-cells in this entity requires additional study.