JAK2 R683S Mutation Resulting in Dual Diagnoses of Chronic Eosinophilic Leukemia and Myelodysplastic/Myeloproliferative Overlap Syndrome.

A 66-year-old male presented with hypereosinophilia, thrombocytosis, extensive thrombosis refractory to direct oral anticoagulant therapy, and evidence of end-organ damage, including rash, splenic infarcts, and pulmonary infiltrates. Bone marrow biopsy revealed myeloid malignancy consistent with both chronic eosinophilic leukemia and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) with SF3B1 mutation and thrombocytosis. Next-generation sequencing of the patient's eosinophils and neutrophil compartments revealed pathologic variants in EZH2 and SF3B1 in addition to a noncanonical JAK2 R683S mutation that has not been previously described in myeloproliferative disorders or other chronic myeloid neoplasms. These mutations were not present in the patient's lymphoid cell fraction, suggesting that the hematopoietic malignancy arose in a myeloid-committed progenitor cell. Based on this case and previous work from our group, we propose that noncanonical JAK2 mutations may permit signal transduction that biases toward eosinophilic differentiation in chronic myeloid neoplasms. Although the patient's blood counts initially responded to ruxolitinib and hydroxyurea, the response was not durable. Early referral for allogenic bone marrow transplant appears necessary to prevent long-term complications and disease progression in myeloid neoplasms with clonal hypereosinophilia driven by noncanonical JAK2 mutations.

A Single-Institution Cohort Study With Nevi of Special Site: Recurrence, Progression to Melanoma, and Patterns of Management.

ABSTRACT: Nevi of specialized sites (NOSS) occur on the scalp, ears, flexural, acral, and genital areas and display atypical clinical and histologic features. We assessed NOSS recurrence and progression to melanoma, management patterns, and associations between histologic features and treatment recommendations. We queried all histologic diagnoses of NOSS (n = 275) from 2012 to 2017 from a large U.S. academic medical center with reference dermatopathology laboratory and matched these to clinical records. A blinded panel of dermatopathologists re-evaluated lesions, catalogued histologic findings, and gave management recommendation. Associations with dermatopathologist decision and concordance between new and original recommendations were assessed. Of 117 cases with follow-up, 2 locally recurred (1.46%) and none eventuated in melanoma. Clinical features were not associated with original treatment recommendations. After histopathologic review, large melanocytes [odds ratio ratio (ORR) = 8.00, 95% CI, 1.35-47.4] and junctional mitotic figures (ORR = 65.0, 6.5-650) predicted excision recommendation. Likewise, accumulation of many (>9) high-risk features was associated with excision recommendation. Panel review changed treatment recommendation in 27% of cases. Fair concordance existed between original and panel recommendations (κ = 0.29, 0.15-0.44). The low rate of recurrence and lack of melanoma occurrence suggest that despite an atypical clinical and histopathologic appearance, these nevi have limited potential for malignant transformation. Histopathologic findings seem to be principal drivers behind the recommendation for excision in this analysis. Variability existed in treatment recommendations; the panel's consensus recommendation tended to downgrade treatment. This highlights the importance of further outcomes-based studies to identify true high-risk features and refine management guidelines.

Pretibial Pruritic Papular Dermatitis: A Comprehensive Clinical and Pathologic Review of Cases at a Single Institution.

BACKGROUND: Studies characterizing clinical and pathologic details of pretibial pruritic papular dermatitis (PPPD) are scarce. Several cases of PPPD at our institution have displayed lymphocyte atypia and CD30 positivity, resembling lymphomatoid papulosis (LyP). We explore the clinical and histological spectrum of PPPD, with emphasis on lymphocyte atypia. METHODS: Retrospective observational study of 40 archived pathological specimens (hematoxylin/eosin, CD3, CD20, and CD30 immunohistochemistry) from 38 PPPD patients in an academic center. Clinical photographs were available in 22 cases. RESULTS: Microscopic epidermal changes were focal, but common (spongiosis 75%, parakeratosis 90%, interface changes 43%, Langerhans cell microgranulomas 25%, multinucleated keratinocytes 55%, Civatte bodies 55%, erosion 20%, and more than focal irregular psoriasiform hyperplasia 37%) and certain dermal changes were universal (papillary dermal fibrosis 100%, stellate fibroblasts 100%, and multinucleated fibroblasts 93%). At least focal lymphocyte atypia was present in all cases. Lymphocytes were almost exclusively CD3 T cells with rare CD20 B cells. Up to 30% of lymphocytes exhibited weak CD30 staining. Clinically, all cases exhibited discrete papules, but plaques and erosions were not uncommon. LIMITATIONS: As a retrospective series, clinical images were not available for all cases. CONCLUSION: This study suggests a broader histological and clinical spectrum of PPPD than previously described. Epidermal changes are common in PPPD, as are atypical lymphocytes and focal CD30 positivity. Although the papular clinical appearance, lymphocyte atypia, and focal CD30 positivity may resemble LyP, the relatively low number of atypical lymphocytes, low intensity of CD30 staining, and absence of spontaneous resolution help to distinguish PPPD from LyP.

Histopathologic vasculitis from the periulcer edge: A retrospective cohort study.

BACKGROUND: Histopathologic vasculitis is often reported in periulcer specimens, but the frequency and clinical significance of this finding have not been evaluated. OBJECTIVE: We evaluated the sensitivity, specificity, negative predictive value, and positive predictive value of histopathologic vasculitis from the periulcer edge for detecting ulcers due to cutaneous vasculitis. METHODS: We performed a retrospective chart review of patients with leg ulcers at a tertiary hospital between 2009 and 2016. Histopathologic slides were evaluated by 2 dermatopathologists who were blinded to the etiology of ulcer. Focal vasculitis was defined as involvement of fewer than 3 vessels. RESULTS: Vasculitis at the periulcer edge was seen in 51.6% of the specimens (32 of 62). Of the specimens with histopathologic vasculitis, focal vasculitis was seen in the majority of specimens (71.9% [23 of 32]), whereas diffuse vasculitis was observed in 28.1% (9 of 32). Periulcer vasculitis yielded a high sensitivity (100% [95% confidence interval, 29%-100%]). Furthermore, the specificity was low (50.9% [95% confidence interval, 38.1%-63.6%]) for detecting vasculitis-induced ulcers. LIMITATIONS: Small number of vasculitis-induced ulcers. CONCLUSION: Focal vasculitis from the periulcer edge is a nonspecific finding and provides little diagnostic value in determining the etiology of lower leg ulcers. Emphasis should be placed on the combination of clinical history and examination, histology, and laboratory findings when diagnosing ulcers.

Cutaneous carcinosarcoma: a series of six cases and a review of the literature.

BACKGROUND: Cutaneous carcinosarcoma is a rare tumor with distinct malignant epithelial and mesenchymal cell populations. The histologic subtypes of epithelial and mesenchymal components in cutaneous carcinosarcoma are variable, as an assortment of carcinomatous and sarcomatous patterns have been described in the literature. METHODS: Clinical information was obtained from patient charts and archival slides were retrieved and reviewed. RESULTS: We present a novel series of six distinct cases of cutaneous carcinosarcoma and review the literature. Our cases consisted of basal cell, pilomatrical, squamous cell, and trichoblastic variants. These cases occurred in elderly men on sun exposed skin with treatment and follow up was available for 4 of 6 cases. The four cases were treated with Mohs micrographic surgery with mean follow up of nine months. CONCLUSION: We report six cases of cutaneous carcinosarcoma with distinctive clinical and histologic characterization not previously described in a single series.

Benign melanocytic lymph node deposits in the setting of giant congenital melanocytic nevi: the large congenital nodal nevus.

BACKGROUND: Benign melanocytic rests are a frequent finding in superficial lymph nodes removed during sentinel lymph node biopsies for melanoma. Whereas the histopathology of these deposits is well understood, very little is known regarding melanocytic lymph node deposits in the setting of giant congenital melanocytic nevi. METHODS: We analyzed lymph nodes removed from the drainage basin of giant congenital melanocytic nevi in three patients who had developed melanoma within their giant congenital nevi. RESULTS: Two of three patients showed widespread, capsular and parenchymal melanocytic deposits in multiple nodes (9 of 11 nodes in one patient and 6 of 8 in the other). Melanocytes were small, non-mitotically active and resembled those in the associated giant congenital melanocytic nevus. Melanocytes were arranged singly and in small nests ∼0.05 mm in diameter, with some larger sheets up to 1 mm. Nodal melanocytes stained for Melan A and S100 on immunohistochemical evaluation, but showed negative or minimal HMB-45 reactivity. CONCLUSIONS: Evaluation of lymph nodes in the setting of giant congenital melanocytic nevi is complicated by the presence of often numerous, parenchymal melanocytic nevic deposits. Bland cytology and minimal or absent HMB-45 staining may be helpful in differentiating these nodal melanocytic nevi from metastatic melanoma. We term this phenomena large congenital nodal nevus.

Neutrophilic sebaceous adenitis with intralobular Demodex mites: a case report and review of the literature.

A 61-year-old white man presented with a 1-week history of an asymptomatic erythematous, annular plaque with minimal scale limited to the nasal bridge. Histological examination showed a mixed infiltrate of lymphocytes and neutrophils within sebaceous glands. The clinical and histopathological presentation was consistent with a diagnosis of neutrophilic sebaceous adenitis. Several Demodex brevis mites were present deep within the affected sebaceous lobules. Demodex brevis mites are uncommon inhabitants of sebaceous glands of the nose, presenting more commonly on other body sites. The cause of neutrophilic sebaceous adenitis is unknown, but the presence of D. brevis in affected sebaceous glands in this case suggests a possible association.

Resident Rounds: Part III - Case Report: Argyria ­ A Case of Blue-Gray Skin.

Argyria is an uncommon blue-gray pigmentation of the skin (increased in sun-exposed areas), nail unit, and mucous membranes caused by prolonged silver exposure. Commonly occurs in the setting of occupational exposure, silver-containing medications, or systemic absorption from use of silver sulfadiazine on extensive burns/wounds. Recently, there appears to be an increase in the practice of colloidal silver ingestion given the popularity and easy availability of alternative medicines and dietary supplements containing various silver-containing compounds. We report a case of argyria in a 72-year-old male following ingestion of colloidal silver as a supplement for over 10 years. He had a diffuse, blue-gray discoloration of his face and nails. A skin biopsy was performed and histology supported the clinical diagnosis of argyria. Our objective is to increase the awareness for this rare dermatologic entity by highlighting the clinical and histological features through a case report. Dermatologists should warn patients in regards to the use of colloidal silver for alternative health practices.

Polarizable elements in scabies infestation: a clue to diagnosis.

The diagnosis of scabies infestation is straightforward in cases where mite parts are largely visible; however, mites are often not captured in a specimen's planes of section. Polariscopic examination is a fast and simple adjunctive diagnostic tool to light microscopy. We describe the unique polariscopic findings in scabies infestation. Two cases of crusted scabies and eight cases of typical scabies were subjected to polariscopic examination. Diagnostic mite parts were visualized in at least one section in all cases. Attached and detached spines as well as scybala (fecal material) are polarizable. Specifically, spines show a polarizable outer sheath with dark central core while scybala show peripherally concentrated, stippled birefringence. Similar stippled birefringence is visible within the gut of some mites whereas significant birefringence is not appreciated in other mite parts. These results suggest that polariscopic examination is a helpful clue in the diagnosis of scabies infestation, especially in cases where the body of the mite is not visualized.

Use of proliferation rate, p53 staining and perforating elastic fibers in distinguishing keratoacanthoma from hypertrophic lichen planus: a pilot study.

BACKGROUND: Distinguishing keratoacanthoma (KA) and hypertrophic lichen planus (LP) histopathologically can be difficult, and the challenge is compounded by the tendency of KA to arise in association with hypertrophic LP. METHODS: In this pilot study, we compared 18 cases each of KA and hypertrophic LP for proliferation index (MIB-1), p53 staining and the presence of perforating elastic fibers (elastic Verhoeff-van Gieson) to determine the utility of these staining modalities in distinguishing KA from hypertrophic LP. RESULTS: Proliferation index in KA compared to hypertrophic LP is 88.2 (mean positive MIB-1 cells/×100 field), SD = 56.6 and 47.3, SD = 68.4, respectively. p53 staining in KA compared to hypertrophic LP is 251 (mean positive cells/×100 field), SD = 117 and 158, SD = 119, respectively. Fifteen of eighteen (83%) keratoacanthomata demonstrate perforating elastic fibers compared to 1/18 (6%) for hypertrophic LP. CONCLUSION: Proliferation index is not significantly different between KA and hypertrophic LP (p = 0.059). Expression of p53 is increased in KA over hypertrophic LP (p = 0.024). The presence of perforating elastic fibers in KA is significantly different from hypertrophic LP (p < 0.0001) and suggests that elastic Verhoeff-van Gieson staining may be of practical benefit in distinguishing KA from hypertrophic LP in difficult cases.

Immunohistochemical staining with Melan-A of uninvolved sun-damaged skin shows features characteristic of lentigo maligna.

BACKGROUND: The greater density and unusual patterning of melanocytes in chronically sun-exposed skin complicates interpretation of intraoperative Melan-A immunohistochemical stained margins during margin-controlled surgery for lentigo maligna (LM) and lentigo maligna melanoma (LMM). OBJECTIVE: To identify the immunohistochemical similarities and differences in melanocyte distribution between LM and LMM and chronically sun-exposed skin. METHODS: Retrospective review of Melan-A-stained original biopsy specimens of LM and LMM and uninvolved sun-damaged skin (negative controls), from 70 LM and LMM cases from the University of Utah in 2008. RESULTS: Histologic features commonly associated with LM were common in negative controls from chronically sun-exposed skin. Melanocyte confluence (27/70, 39%), stacking (34/70, 49%), theque formation (9/70, 13%), adnexal extension (59/68, 87%), and suprabasilar scatter (23/70, 33%) were observed in the negative controls from sun-damaged skin. Such features were present nearly uniformly in the LM and LMM specimens. Epidermal melanocyte density in LM and LMM differed significantly from that in negative controls (82.7 ± 29.3 and 25.6 ± 9.3 per × 400 field, respectively; p<.001). CONCLUSION: Epidermal melanocytic features often ascribed to LM, such as melanocyte confluence, stacking, theque formation, adnexal extension, and suprabasilar scatter, are frequently observed in chronically sun-exposed Caucasian skin and may lead to overestimation of surgical margins.

Orf parapoxvirus infection from a cat scratch.

A 53-year-old woman presented with an enlarging, tender, ulcerated nodule on her dorsal hand after being scratched by a stray kitten. Histology was consistent with orf parapoxvirus infection. The lesion resolved without scarring after several weeks of treatment with imiquimod 5 percent cream. Orf is a zoonosis transmitted to humans from sheep and goats by direct contact or by fomites. Transmission by cat scratch has not been previously described in the literature.

Severe retention hyperkeratosis occurring with Susac syndrome.

A 50-year-old woman presented for asymptomatic yellow hyperkeratotic plaques limited to her face. The plaques reportedly arose over the six months prior to her clinic visit. She was healthy prior to the diagnosis of Susac syndrome (retinocochleocerebral vasculopathy) two years before. A punch biopsy was performed and revealed retention hyperkeratosis. Retention hyperkeratosis is a benign and commonly seen skin condition in primary care and dermatology. Retention hyperkeratosis occurs when there is abnormality of routine desquamation that can be associated with poor hygeine. It can be associated with acne or ichthyosis. Our case of retention hyperkeratosis is unique because of the profound presentation in a setting of an untreated psychiatric condition. Treatment consisted of daily topical exfoliative care. We also encouraged her family members to help her to seek medical attention for Susac syndrome.

The role of vulvar skin biopsy in the evaluation of chronic vulvar pain.

Sixty-one percent of refractory vulvodynia patients evaluated in a tertiary care vulvovaginal clinic had clinically relevant dermatoses based on dermatopathologist-analyzed vulvar biopsy including: lichen sclerosus, allergic/irritant dermatitis, lichen planus, and other inflammatory or neoplastic dermatoses. Given the frequency of dermatologic disease, vulvar biopsy and analysis by a dermatopathologist are recommended in patients with vulvodynia.