Digital dermatopathology implementation: Experience at a multisite academic institution.

BACKGROUND: Technology has revolutionized not only direct patient care but also diagnostic care processes. This study evaluates the transition from glass-slide microscopy to digital pathology (DP) at a multisite academic institution, using mixed methods to understand user perceptions of digitization and key productivity metrics of practice change. METHODS: Participants included dermatopathologists, pathology reporting specialists, and clinicians. Electronic surveys and individual or group interviews included questions related to technology comfort, trust in DP, and rationale for DP adoption. Case volumes and turnaround times were abstracted from the electronic health record from Qtr 4 2020 to Qtr 1 2023 (inclusive). Data were analyzed descriptively, while interviews were analyzed using methods of content analysis. RESULTS: Thirty-four staff completed surveys and 22 participated in an interview. Case volumes and diagnostic turnaround time did not differ across the institution during or after implementation timelines (p = 0.084; p = 0.133, respectively). 82.5% (28/34) of staff agreed that DP improved the sign-out experience, with accessibility, ergonomics, and annotation features described as key factors. Clinicians reported positive perspectives of DP impact on patient safety and interdisciplinary collaboration. CONCLUSIONS: Our study demonstrates that DP has a high acceptance rate, does not adversely impact productivity, and may improve patient safety and care collaboration.

Utilization of skin biopsy for diagnosis in a case of Lafora disease.

Lafora disease is a rare inherited neurodegenerative disease with onset in adolescence. Patients present with progressive myoclonic seizures and cognitive decline. The disease is linked to mutations in either of the two genes encoding malin and laforin, and it is associated with the accumulation of polyglucosan inclusions (Lafora bodies [LBs]) in various tissues, such as brain, liver, muscle, and skin, with the skin being particularly accessible for biopsy. Histopathologic examination of affected tissue with demonstration of LBs, together with the presence of pathologic mutation in EPM2A or NHLRC1 genes, is sufficient for diagnosis of this neurologic disorder when clinically suspected. Here, we report the case of a 16-year-old female with progressive neurologic symptoms and homozygous mutation in the NHLRC1 gene encoding malin. The skin biopsy was instrumental in reaching the final diagnosis by showing LBs in sweat glands by histopathologic and electron microscopic examination.

Impact of adding an IgG4 conjugate to routine direct immunofluorescence testing for subepithelial and intraepithelial autoimmune blistering disorders.

BACKGROUND: Certain autoimmune bullous dermatoses are mediated by autoantibodies of the IgG4 subclass. We determined the diagnostic impact of adding IgG4 to our conventional direct immunofluorescence (DIF) panel. METHODS: For all cases submitted to our referral laboratory for DIF over 1 month (n = 630), we performed IgG4 testing and collected consecutive biopsy specimens showing definite or indeterminate linear or cell-surface deposition of IgG, IgG4, and/or C3. On retrospective blinded review, we classified the pattern and whether the findings were definite, indeterminate, or negative. When present, substantial background staining was recorded. RESULTS: Seventy DIF specimens met the inclusion criteria. Of 22 (31.4%) specimens equivocal for linear or cell-surface deposition, 9 (40.9%) had definitive IgG4 findings, either linear (3 of 14 equivocal linear cases; 21.4%) or cell-surface (6 of 8 equivocal cell-surface cases; 75.0%). Background deposition was substantial in 14 cases (20.0%) for IgG but in none for C3 or IgG4. CONCLUSION: IgG4 allowed the classification of over 40% of DIF cases that were otherwise equivocal by IgG and C3. IgG4 staining showed lower levels of non-specific background staining than IgG or C3. IgG4 appears to contribute most value in cases with cell-surface deposition or with equivocal linear IgG deposition and negative C3 results.

Primary Cutaneous Enteric Duplication Cyst: A Novel Entity.

ABSTRACT: Enteric duplication cysts (EDCs) are rare congenital malformations consisting of double-walled cystic or tubular structures lined by gastrointestinal type epithelium. EDCs share a common muscular wall and blood supply with the adjacent duplicated bowel with very rare exceptions. The majority of EDCs are intraabdominal with cases less commonly intrathoracic or thoracoabdominal. To the best of our knowledge, we present the first reported case of primary cutaneous EDC to occur outside the abdominal and thoracic cavities. A 17-year-old male without a significant medical or surgical history underwent excision of a cystic nodule on the left hip. On histopathology, a dermal to subcuticular cyst exhibited an epithelial lining with 2 distinct components including cuboidal to columnar mucinous cells (CK7+, CK20-, and CDX2-) and complex glandular colonic-type mucosa (CK7-, CK20+, and CDX2+). A thick muscular wall resembling muscularis mucosa and muscularis propria surrounded the cyst. Findings supported a primary cutaneous enteric duplication cyst of uncertain developmental etiology. The novel nature of this entity could represent a diagnostic challenge.

A rare case of childhood mucous membrane pemphigoid involving the oral and genital mucosa.

Mucous membrane pemphigoid (MMP) is a rare chronic immunobullous disease that involves the mucous membranes and may result in significant scarring and complications if diagnosis is delayed. MMP typically occurs in elderly patients, with very few cases reported in children. Here, we present a 12-year-old female patient with childhood-onset oral and genital MMP, clinically suspected to be lichen sclerosus, but eventually diagnosed as MMP after multiple supportive biopsies and confirmatory direct immunofluorescence. Although treatment was challenging, the combined use of systemic corticosteroids, dapsone, and mycophenolate mofetil was ultimately successful in achieving disease control.

Acral localized acquired cutis laxa as presenting sign of underlying systemic amyloidosis.

Acral localized acquired cutis laxa (ALACL) is a rare variant of acquired cutis laxa, and the clinical appearance is characterized by loose, redundant and wrinkled skin of the distal extremities. By definition, histopathology of affected tissue reveals sparse or fragmented elastic fibers. However, this can be difficult to assess on routine staining, and sometimes requires electron microscopy. The condition has been associated with plasma cell dyscrasias or recurrent inflammatory states. We present a case of a 65-year-old man who presented with enlarged and doughy finger pads. Skin biopsy showed diffuse dermal amyloid deposition displacing dermal stroma and reduction of elastic fibers, although these changes were subtle on routine hematoxylin and eosin staining. Mass spectrometry of laser capture microdissected tissue showed AL kappa-type amyloid and further workup revealed a diagnosis of primary systemic AL-kappa amyloidosis requiring bone marrow transplantation. This case represents an unusual presentation of acquired cutis laxa and highlights the need for a high index of suspicion when reviewing histopathology of this entity. In addition, the case highlights the importance of investigation into possible systemic associations, such as plasma cell dyscrasias.

Circulating bullous pemphigoid autoantibodies in the setting of negative direct immunofluorescence findings for bullous pemphigoid: A single-center retrospective review.

BACKGROUND: Bullous pemphigoid (BP) autoantibody levels are generally elevated in patients with BP but can be present nonspecifically in patients without BP. OBJECTIVE: To analyze the clinical findings of patients with elevated BP180 or BP230 autoantibody levels and negative direct immunofluorescence (DIF) study findings. METHODS: We retrospectively reviewed records of patients seen at our institution during January 1, 2005-December 31, 2015, who were positive for BP180 or BP230 autoantibodies and had a negative DIF study finding. These patients' demographic characteristics and BP180 and BP230 levels were compared with those of a BP control group who were positive for BP180 or BP230 autoantibodies and had positive DIF study findings. RESULTS: We identified 208 patients with BP autoantibodies but without positive DIF study findings. These patients' mean age and enzyme-linked immunosorbent assay values were significantly lower than those of the control group. Dermatitis was the most common final clinical diagnosis. Of the 208 patients, 41 (19.7%) had at least 2 years' follow-up. Four patients had positive DIF results upon repeating the test and ultimately received pemphigoid diagnoses. LIMITATIONS: Retrospective design with limited follow-up. CONCLUSION: Patients might harbor serum BP autoantibodies in the context of a wide range of dermatoses. Low positive BP180 and BP230 autoantibody levels should not be overinterpreted as evidence for BP in the setting of a negative DIF.

Clinicopathologic and immunophenotypic features of eosinophilic fasciitis and morphea profunda: A comparative study of 27 cases.

BACKGROUND: Eosinophilic fasciitis (EF) and morphea profunda (MP) are inflammatory and sclerosing disorders of the subcutis that can exhibit clinical and pathologic presentations that overlap. OBJECTIVE: To identify clinicopathologic features that can be used to distinguish EF from MP. METHODS: We performed a retrospective review of 16 patients with EF and 11 patients with MP. Hematoxylin-eosin, CD123, CD34, and Verhoeff-Van Gieson stains were evaluated on skin biopsies that included the fascia. RESULTS: EF patients were more likely than MP patients to be men (P = .047), have forearm involvement (P = .003), and have peripheral eosinophilia (P < .01). Compared with MP patients, patients with EF were more likely to have fascia that contained eosinophils (P = .003), although eosinophils were absent in 3 (19%) patients with EF. Focal absence of CD34 staining was more prominent in the fascia of EF patients (P = .04). The extent of Verhoeff-Van Gieson staining did not differ between the 2 groups. Dermal sclerosis was not detected in many cases of EF and MP (56% and 36%, respectively). LIMITATIONS: This was a retrospective study at a single institution. CONCLUSION: Although EF and MP share clinical and pathologic features, our results indicate that the presence of eosinophils in the blood and fascia and focal loss of CD34 staining might be more suggestive of EF than MP.

Clinical and histopathologic manifestations of solid organ transplantation-associated graft-versus-host disease involving the skin: A single-center retrospective study.

BACKGROUND: Graft-versus-host disease (GVHD) following solid organ transplantation (SOT) is extremely rare and infrequently described in the dermatologic literature. METHODS: We performed a retrospective clinicopathologic review of our institution's experience with patients diagnosed with SOT-associated GVHD (SOT GVHD) (May 1, 1996 to September 1, 2017). RESULTS: Of nine patients with SOT GVHD, seven had undergone liver transplantation, while two had undergone lung transplantation. All presented initially with a skin eruption, which developed an average of 63 days (range: 11-162 days) post transplant. The average time to diagnosis following the onset of the skin eruption was 12 days (range: 0-54 days). Diagnosis was often delayed because of a competing diagnosis of drug reaction. Frequent skin findings included pruritic erythematous to violaceous macules and papules with desquamation. Histopathology showed vacuolar interface dermatitis in 12 of 15 cases (80.0%). Of the 11 specimens in which a hair follicle was present for evaluation, vacuolar interface changes around the hair follicle were present in eight (72.7%) cases. Seven patients (77.8%) died from complications during the follow-up period. CONCLUSIONS: SOT GVHD presents initially with skin involvement, is associated with vacuolar interface changes on skin biopsy, and is associated with a high mortality rate. Clinicopathologic correlation is required for accurate diagnosis.

Amicrobial pustulosis of the folds: Report of 4 cases.

Amicrobial pustulosis of the folds (APF) is a rare disease characterized by aseptic pustular lesions involving cutaneous folds, typically occurring in the context of an autoimmune disorder. We present 4 patients with APF, focusing on clinical and histopathologic characteristics to improve the recognition of this entity. All 4 patients had intertriginous and extra-intertriginous involvement. Common histopathologic features of skin biopsies in these patients were intracorneal, subcorneal, intraepidermal, perivascular, perifollicular and interstitial neutrophilic inflammation. Pustules overlying adnexal ostium and papillary dermal edema were consistently observed. The pustules were negative for microorganisms on stain testing. In these cases, associated conditions were undifferentiated connective tissue disease, systemic lupus erythematosus, antiphospholipid syndrome, Crohn disease and Hashimoto thyroiditis. The aforementioned clinical and histopathologic characteristics of patients with suspected or diagnosed connective tissue disorders should lead to suspicion for APF.

Dermatomyofibromas Arising in Children: Report of Two New Cases and Review of the Literature.

Dermatomyofibroma is a rare, benign mesenchymal proliferation not commonly reported in children. Two patients with biopsy-proven dermatomyofibroma were identified (one female, one male) at our institution, both with rather atypical clinical presentations. The clinical and histopathologic findings and a review of the literature are presented here. Features of dermatomyofibroma should be recognized and differentiated from those of similar-appearing entities since the prognosis of this benign tumor is favorable after complete excision.

Head and neck desmoplastic melanoma: Utility of sentinel node biopsy.

PURPOSE: The utility of sentinel lymph node biopsy in desmoplastic melanoma has been questioned due to multiple reports of a low rate of occult nodal metastasis in this variant of melanoma. We describe a single institution experience with management of desmoplastic melanoma of the head and neck and discuss the utility of sentinel lymph node biopsy. MATERIALS AND METHODS: A retrospective review was performed of 49 patients with desmoplastic melanoma of the head and neck at a tertiary care center from 1994 to 2014. RESULTS: Sentinel lymph node biopsy was performed in 15 patients. Only 1 (6.7%) of these patients was found to have a positive sentinel node. Of the 46 patients without evidence of neck disease at presentation, 3 (6.5%) were found to have occult nodal disease or developed neck recurrences. When looking at the entire cohort, there were a total of 16 recurrences in 14 patients (28.6%). The majority (85.7%) of recurrences were either local or distant metastasis with only 2 (14.3%) recurrences being in regional lymph node basins. The overall rates of local, regional, and distant recurrences were 14.2%, 4.1%, and 10.2% respectively. The mixed pathologic subtype was not associated with a higher rate of nodal metastasis. CONCLUSIONS: Desmoplastic melanoma has a low rate of occult nodal metastasis and a high propensity to recur locally or as a distant metastasis, regardless of regional node status. Our experience combined with the uncertain impact that sentinel node status has on survival raises the question of the utility of routine sentinel node biopsy in this specific variant of melanoma.

Validation of diagnostic accuracy with whole-slide imaging compared with glass slide review in dermatopathology.

BACKGROUND: Teledermatopathology has evolved from static images to whole slide imaging (WSI), which allows for remote viewing and manipulation of tissue sections. Previous studies of WSI in teledermatopathology predated College of American Pathologists (CAP) telepathology validation guidelines. OBJECTIVE: We conducted a comprehensive retrospective WSI validation study of routine dermatopathology cases, adhering to CAP guidelines. METHOD: In all, 181 consecutive cases arranged into 3 categories (inflammatory, melanocytic, nonmelanocytic proliferations) were reviewed by 3 board-certified dermatopathologists via traditional microscopy (TM) and WSI. Intraobserver (TM vs WSI), TM intraobserver and interobserver (TM vs TM), and WSI interobserver (WSI vs WSI) concordance was interpreted using a 3-tier system. RESULTS: TM versus WSI intraobserver concordance (86.9%; 95% confidence interval [CI] 83.7-89.6) did not differ from TM versus TM intraobserver concordance (90.3%; 95% CI 86.7-93.1) or interobserver concordance (WSI: 89.9%; 95% CI 87.0-92.2, and TM: 89.5%; 95% CI 86.5-91.9). Melanocytic proliferations had the lowest TM versus WSI intraobserver concordance (75.6%; 95% CI 68.5-81.5), whereas inflammatory lesions had the highest TM versus WSI intraobserver concordance (96.1%; 95% CI 91.8-98.3). Nonmelanocytic proliferations had an intraobserver concordance of 89.1% (95% CI 83.4-93.0). LIMITATIONS: Efficiency and other logistical WSI parameters were not evaluated. CONCLUSION: Intraobserver and interobserver diagnostic concordance between WSI and TM was equivalent. Therefore, WSI appears to be a reliable diagnostic modality for dermatopathology.

Frequency of cutis laxa-like clinical features and elastolysis in scleromyxedema: a retrospective clinicopathologic study of 19 patients with scleromyxedema.

BACKGROUND: Cutis laxa-like features were observed in a subset of patients with scleromyxedema. Given this observation, clinical and histopathologic features of scleromyxedema were reviewed in correlation with elastic tissue staining. METHODS: We retrospectively reviewed clinical records and histopathologic features from patients with scleromyxedema seen at our institution from 1992 through 2013. We also evaluated available skin biopsies with an elastin stain and assessed whether dermal elastin fibers were diminished in density or were fragmented (or both). RESULTS: Nineteen patients with scleromyxedema and 34 skin biopsies were identified. Alcian blue (mucin) stain was used to grade mucin deposition as weakly positive (24%), positive (44%) and markedly positive (32%). Eight patients (42%) had clinical findings of cutis laxa, which were often observed in conjunction with areas of papular eruption or induration. Elastic tissue fibers were normal in 9 of 34 skin specimens (26%), 18 of 34 specimens (53%) had diminished elastic fiber density and 7 of 34 (21%) had markedly decreased density. The elastic tissue was fragmented in 25 specimens (74%). CONCLUSIONS: A cutis laxa-like clinical presentation and decreased elastic tissue density on skin biopsy were consistent findings. Dermatologists and dermatopathologists should be aware of these previously unreported clinical and histopathologic findings.

A Primary Cutaneous CD30-Positive T-Cell Lymphoproliferative Disorder Arising in a Patient With Multiple Myeloma and Cutaneous Amyloidosis.

CD30-positive cutaneous lymphoproliferative disorders, a group of T-cell neoplasms, including lymphomatoid papulosis (LyP) and cutaneous anaplastic large cell lymphoma, require careful clinicopathologic correlation for diagnosis. An association between LyP and the development of a second hematolymphoid malignancy has been established in the literature. LyP has also been reported with systemic amyloidosis, but no such reports have documented coexisting cutaneous amyloid deposition with LyP to our knowledge. A 66-year-old woman with cutaneous amyloidosis, secondary to multiple myeloma, in remission, presented with erythematous and dark-brown papules involving the right arm, scalp, and torso. Punch biopsy of the arm showed a dermal infiltrate of intermediate-sized lymphocytes, some of which displayed a plasmacytoid morphology and prominent nodular subepidermal amyloid deposition. Punch biopsy of the scalp similarly showed a nonepidermotropic dense dermal infiltrate of intermediate-sized plasmacytoid lymphocytes and multifocal amyloid deposition. Both infiltrates were immunophenotypically CD30-positive, anaplastic lymphoma kinase-negative T-cell lymphoproliferative processes. Subsequent studies showed no systemic involvement, and clinical correlation suggested a final diagnosis of LyP. We present this case of LyP, which histologically mimics a B-cell proliferation with a plasmacytoid morphology arising in association with cutaneous amyloidosis to highlight the importance of clinicopathologic correlation, a thorough battery of immunohistochemical studies, and consideration for a second hematologic malignancy arising in the setting of LyP.

Penile and Scrotal Swelling: An Underrecognized Presentation of Crohn's Disease.

BACKGROUND: Penile and scrotal swelling can occur as an extraintestinal manifestation of Crohn's disease (CD) and is thought to be an uncommon form of metastatic CD (MCD). Because of the rarity of this manifestation, much is unknown concerning the presentation, treatment, and response to therapy in children with genital MCD. METHODS: Boys ages 1 to 17 years presenting with genital edema and a confirmed diagnosis or strong suspicion of CD who were evaluated at the Mayo Clinic between 1996 and 2014 were included for review. We sought to characterize the clinical and pathologic features of genital MCD and response to treatment in our cohort of patients. RESULTS: Eight patients with genital MCD were identified from our institution (mean age 11.4 yrs, range 7-16 yrs). Seven (88%) patients experienced cutaneous symptoms before a formal diagnosis of CD was made, and two of the seven had no adverse gastrointestinal symptoms at that time. Patients were prescribed an average of 3.4 medications (topical and systemic) for management of their gastrointestinal CD and MCD. CONCLUSIONS: Penile and scrotal swelling can occur as an extraintestinal manifestation of CD and is thought to be an uncommon form of MCD. In boys, genital swelling typically precedes intestinal CD. Treatment of the underlying CD with systemic medications was most helpful in this series. An evaluation for CD is necessary in all patients presenting with unexplained genital swelling.

Incidence of bullous pemphigoid and mortality of patients with bullous pemphigoid in Olmsted County, Minnesota, 1960 through 2009.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune blistering disease that is associated with increased mortality. OBJECTIVE: We sought to determine the incidence and mortality of patients with BP. METHODS: A total of 87 residents of Olmsted County, Minnesota, were identified who had their first lifetime diagnosis of BP from January 1960 through December 2009. Incidence and mortality were compared with age- and sex-matched control patients from the same geographic area. RESULTS: The adjusted incidence of BP was 2.4 per 100,000 person-years (95% confidence interval, 1.9-2.9). Incidence of BP increased significantly with age (P < .001) and over time (P = .034). Trend tests indicate increased diagnosis of localized disease (P = .006) may be a contributing factor. Survival observed in the incident BP cohort was significantly poorer than expected (P < .001). Survival was not different among patients with multisite versus localized disease (P = .90). LIMITATIONS: Retrospective study design and study population from a small geographic area are limitations. CONCLUSION: Incidence of BP in the United States is comparable with that found in Europe and Asia. The mortality of BP is lower in the United States than Europe, but higher than previous estimates.