Chronic Progressive Pink-Yellow Papules and Nodules in a Middle-Aged Man.

A 38-year-old man presented with numerous pink-yellow firm papules and nodules on the bilateral elbows for 10 years spreading to the hands and knees in the past year. What is your diagnosis?

IDH2-mutated near ETP-ALL with aggressive leukemia cutis and brisk response to venetoclax and decitabine.

Near early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a rare hematologic malignancy, for which second line therapeutic options are limited. T-cell leukemias are also rarely associated with leukemia cutis, which is more often seen in leukemias of myeloid origin. We present the case of an adult male diagnosed with near ETP-ALL, with IDH2 and DNMT3A mutations, suggestive of a myeloid origin, and leukemia cutis. After the patient progressed on hyper-CVAD and nelarabine, we treated him with the BCL-2 inhibitor venetoclax and the hypomethylating agent decitabine. The regimen induced a rapid bone marrow response and resolution of the leukemia cutis.

Congenital syphilis presenting with granulomatous scalp nodules.

We describe a case of congenital syphilis in an adopted infant with a unique dermatologic presentation of scalp granulomas, along with lymphadenopathy, anemia, and elevated liver transaminases. To our knowledge, this cutaneous morphology has not been previously reported in the literature. This case highlights the varied clinical presentation of congenital syphilis and the diagnostic challenge it poses for clinicians, especially in the context of unknown prenatal history/unknown risk factors, or if syphilis is acquired during pregnancy after routine screening is performed. As the incidence of congenital syphilis has more than tripled in recent years, this diagnosis should be considered when a neonate or infant presents with unexplained skin nodules.

Neurotropic Cutaneous Malignancies: Case Report on Keratinocyte Derived Malignancies of the Head and Neck With Perineural Invasion.

Background: The recent addition of immunotherapy as a treatment modality to surgery and radiation has vastly improved disease control for patients with keratinocyte-derived carcinomas (KCs) that are incurable with local therapies alone. With the advent of immune checkpoint inhibitors (ICPis) in non-melanoma skin cancers comes diagnostic and therapeutic challenges when considering treatment strategies for patients presenting with clinical perineural invasion (cPNI) of locally advanced KC of the head and neck. Objectives: We report four cases that convey the diagnostic and therapeutic complexity of managing patients with neuropathic symptoms from cutaneous neurotropic carcinomas of the head and neck. We also discuss an updated review regarding immunotherapies and perineural invasion within KC management. Conclusion: Patients presenting with symptoms suspicious for cPNI warrant an expanded diagnostic evaluation to correlate neurological findings with neurotropic spread of disease. While nerve biopsies can be precarious in sensitive areas, a history of skin cancer and clinical presentation suggestive of neurotropism may be enough to pursue timely management in the form of surgery, radiation, and/or systemic therapy given each patient's individual priorities, comorbidities, and prognosis. When adding ICPi as a treatment modality for patients with disease not amenable to local therapies, the potential for immune-related adverse events must be considered. A multi-disciplinary review and approach to the management of patients with KC and cPNI is essential for obtaining optimal patient outcomes.

Leukocytoclastic Vasculitis Induced by Immune Checkpoint Inhibition in a Patient With Advanced Renal Cell Carcinoma.

A Mexican woman, aged 60 years, presented with fevers and abdominal pain. She had initially presented to an outside emergency department with weakness, malaise, nausea, vomiting, tachycardia to 110s, and fever to 102 °F. Her medical history was relevant for hypertension, prediabetes, and tobacco use (4-5 cigarettes/day for 12 years). There was no significant family history. Pertinent labs included hemoglobin 8.0 g/dL, white blood cells 13.1 × 109/L, absolute neutrophil count 10.2 × 109/L, creatinine 1.3 mg/dL, calcium 9.2 mg/dL, and lactate dehydrogenase 682 U/L. Initial imaging showed a large 14-cm right renal mass, with tumor in vein in the right renal vein and inferior vena cava, and extensive bilateral pulmonary emboli. A pulmonary thrombectomy was performed, with pathology on the right lung thrombus consistent with metastatic clear cell renal cell carcinoma (RCC), cT4N0M1, categorized as intermediate risk per the International Metastatic RCC Database Consortium.

USP6 rearrangement in pediatric nodular fasciitis.

Nodular fasciitis (NF) is a myofibroblastic proliferation that is uncommonly present in pediatric patients. These benign neoplasms can masquerade as more insidious sarcomatous proliferations on both clinical exam and initial histopathologic review, often prompting undue concern in patients, parents, and providers. While immunohistochemical analysis of NF can be variable, adding to the diagnostic uncertainty, molecular analysis documenting ubiquitin-specific protease 6 (USP6) gene rearrangement can help confirm the diagnosis as an association between NF and USP6 overexpression was first identified 10 years ago in an analysis that found rearrangements of the involved locus in over 90% of studied samples. In this report, we review one case of NF located on the chin of a nine-year-old girl in which molecular testing was essential to secure the correct diagnosis, and provide a summary of documented cases of USP6 overexpression in transient pediatric neoplasms.

Histopathologic and genetic findings in atypical spindle cell/pleomorphic lipomatous tumors and atypical pleomorphic fibromas.

BACKGROUND: Spindle cell lipomas, pleomorphic lipomas (SCL/PLs), and pleomorphic fibromas (PF) are tumors with loss of retinoblastoma (RB). The latest World Health Organization classification includes a category of atypical spindle cell/pleomorphic lipomatous tumors (ASPLT), which encompasses tumors in this spectrum that show atypical histopathologic features. We have observed PFs that show similar atypical features. METHODS: Cases of SCL/PL and PF with atypical features were collected from tissue archives between 2010 and 2019. Genetic alterations were investigated using array comparative genomic hybridization (aCGH). RESULT: Of 15 cases found, most tumors were dermal based with fibrocytic or fibroadipocytic appearance and occasional lipoblasts. All cases had a high proliferation index with atypical mitotic figures in 71% of cases. Chromosome 13q loss was present in all cases with CGH data. Additional recurrent chromosomal losses included 17p, 16q, 17q, 20p, 4, and 10. No recurrence was found in limited follow-up. CONCLUSIONS: ASPLTs are characterized by loss of RB, prominent nuclear pleomorphism, mitotic activity including atypical mitotic figures, and genomic instability with multiple chromosomal aberrations. A similar group of tumors with these histopathologic features lacks lipomatous differentiation, and we propose the diagnosis of atypical PF as a fibromatous variant of ASPLT. Limited clinical follow-up appears benign.

Atypical Presentation of Transcranial Extension of Intracranial Meningiomas.

ABSTRACT: Meningiomas are the most common primary central nervous system tumors. These tumors predominantly arise from the neural crest-derived meningothelial cells of the arachnoid dural layer. Intracranial meningiomas are stratified with the World Health Organization classification of tumors. Cutaneous meningiomas present rarely and have their own criteria classification (Lopez classification) of 3 types. The first type is congenital. The second consists of ectopic soft-tissue meningiomas. The third involves tumors that extended into the dermis or subcutis that include the neuroaxis. We present a case of a 56-year-old woman with 4 facial tumors that clinically seemed to be cutaneous cysts or lipomas. She reported a history of surgical resection of an intracranial meningioma on the left forehead scalp line 15 years ago. A recent surgical resection of a glabellar tumor revealed a glistening white mass. Pathologic examination revealed a poorly circumscribed mass in the deep dermis and subcutaneous area with sheets of epithelioid and plasmacytoid tumor cells with nuclear pleomorphism. Mitotic figures and necrosis were also evident. Immunohistochemistry revealed positivity for epithelial membrane antigen, p63, and ERG. The tissue had negative staining for p40, CK7, SOX10, CD68, SMA, desmin, and CD34. The patient's medical history was remarkable in that these tumors had only been growing for several months. Brain magnetic resonance imaging demonstrated widespread tumors in bilateral frontal lobes, skull, orbits, and sinuses. Considering the transcranial extensions and 15-year recurrence time, she was diagnosed with a recurrent atypical brain meningioma type II and cutaneous meningioma Lopez type III.

Targeting CD70 in cutaneous T-cell lymphoma using an antibody-drug conjugate in patient-derived xenograft models.

CD70 is a member of the tumor necrosis factor receptor superfamily. Emerging data indicate that CD70 may be a suitable target for various malignancies. We investigated the expression of CD70 in cutaneous and systemic T-cell lymphomas and conducted preclinical studies of SGN-CD70A, a CD70-directed antibody-drug conjugate (ADC), using patient-derived xenograft cutaneous T-cell lymphoma (CTCL PDX) models. CD70 expression was examined by immunohistochemical (IHC) stains in 49 diagnostic specimens of T-cell lymphomas. The activities of SGN-CD70A in growth inhibition and apoptosis induction were examined in CTCL cell lines and primary CTCL tumor cells. Using previously established CTCL PDXs, we conducted a dose-finding trial followed by a phase 2-like trial to evaluate the optimal dosing and the efficacy of SGN-CD70A in tumor-bearing PDX animals. The therapeutic efficacy of SGN-CD70A was measured by tumor-associated cell-free DNA (cfDNA) and survival of treated PDXs. We found that CD70 is highly expressed in T-cell lymphomas, especially in CTCL. SGN-CD70A inhibited cell growth and induced apoptosis in CD70-expressing CTCL cell lines and primary tumors cells. Additionally, SGN-CD70A at 100 µg/kg and 300 µg/kg prolonged the survival of PDXs in a dose-dependent manner. Finally, treatment with 3 doses of SGN-CD70A at 300 µg/kg was superior to a single-dose treatment in survival prolongation (median survival: 111 days vs 39 days; P = .017). Most importantly, multiple dosing of SGN-CD70A induced complete eradication of established tumors in PDXs measured by cfDNA. Our results demonstrated marked antitumor activity of SGN-CD70A in CTCL PDXs, providing compelling support for its clinical investigation.

Atypical keratosis pilaris-like lesions in a patient with Bethlem myopathy.

Bethlem myopathy is a collagen VI-related myopathy. Collagen VI is primarily not only associated with the extracellular matrix of skeletal muscle, but is also found in the skin, blood vessels, and other organs. Dermatologic findings described for Bethlem myopathy include follicular hyperkeratosis and abnormal scar formation, although clinical and histopathologic photographs remain elusive in the literature. We present a case of atypical keratosis pilaris-like follicular lesions in a patient with Bethlem myopathy and provide histopathologic correlation to better characterize the development of skin lesions in this rare neuromuscular disease.

Characteristics of Superficial Basal Cell Carcinomas Containing More Aggressive Subtypes on Final Histopathologic Diagnosis.

BACKGROUND: The prognosis and treatment of basal cell carcinoma (BCC) are largely dependent on tumor subtype, which is typically determined by punch or shave biopsy. Data regarding concordance between BCC subtype on initial biopsy and final histopathology for Mohs micrographic surgery (MMS) or excision with frozen sections (EFS) are limited. OBJECTIVES: To determine the concordance between initial biopsy and final MMS or EFS subtyping of BCC. We aim to investigate the incidence and clinical characteristics of lesions initially diagnosed as superficial BCC (sBCC) that are later found to have a nodular, micronodular, or infiltrative component. METHODS: We conducted a retrospective review of all MMS or EFS cases performed at a single academic center from August 1, 2015, to August 31, 2017. Inclusion criteria were a biopsy-proven diagnosis of sBCC and presence of residual tumor following stage I of MMS or EFS. Fisher’s exact test was used to evaluate significance of clinical characteristics and outcomes associated with the presence of a nodular, micronodular, or infiltrative BCC component. RESULTS: A total of 164 MMS or EFS cases had an initial biopsy showing sBCC. Of these, 117 had residual BCC on stage I, and 43 (37%) were found to have a nodular, micronodular, or infiltrative component. Significant predictors of reclassified BCC subtype included age over 60 years (P= 0.006) and location on the head or neck (P=0.043). Reclassified lesions required significantly more stages of MMS to clear (P=0.036). Shave biopsy was used to diagnose 114 (97%) of the included cases. CONCLUSIONS: Over one third of shave biopsies that initially diagnosed sBCC failed to detect a nodular, micronodular, or infiltrative component. Management of biopsy-proven sBCC should take into account the possible presence of an undiagnosed deeper tumor component with appropriate margin-assessment treatment modalities when clinically indicated. J Drugs Dermatol. 2021;20(8):874-879. doi:10.36849/JDD.5838.

Characteristics of Superficial Basal Cell Carcinomas Containing More Aggressive Subtypes on Final Histopathologic Diagnosis.

BACKGROUND: The prognosis and treatment of basal cell carcinoma (BCC) are largely dependent on tumor subtype, which is typically determined by punch or shave biopsy. Data regarding concordance between BCC subtype on initial biopsy and final histopathology for Mohs micrographic surgery (MMS) or excision with frozen sections (EFS) are limited. OBJECTIVES: To determine the concordance between initial biopsy and final MMS or EFS subtyping of BCC. We aim to investigate the incidence and clinical characteristics of lesions initially diagnosed as superficial BCC (sBCC) that are later found to have a nodular, micronodular, or infiltrative component. METHODS: We conducted a retrospective review of all MMS or EFS cases performed at a single academic center from August 1, 2015 to August 31, 2017. Inclusion criteria were a biopsy-proven diagnosis of sBCC and presence of residual tumor following stage I of MMS or EFS. Fisher’s exact test was used to evaluate significance of clinical characteristics and outcomes associated with the presence of a nodular, micronodular, or infiltrative BCC component. RESULTS: A total of 164 MMS or EFS cases had an initial biopsy showing sBCC. Of these, 117 had residual BCC on stage I, and 43 (37%) were found to have a nodular, micronodular, or infiltrative component. Significant predictors of reclassified BCC subtype included age over 60 years (P=0.006) and location on the head or neck (P=0.043). Reclassified lesions required significantly more stages of MMS to clear (P=0.036). Shave biopsy was used to diagnose 114 (98%) of the included cases. CONCLUSIONS: Over one third of shave biopsies that initially diagnosed sBCC failed to detect a nodular, micronodular, or infiltrative component. Management of biopsy-proven sBCC should take into account the possible presence of an undiagnosed deeper tumor component with appropriate margin-assessment treatment modalities when clinically indicated. J Drugs Dermatol. 2021;20(3):283-288. doi:10.36849/JDD.5383.

Congenital cutaneous non-neural granular cell tumor mimicking herpetic infection: Case report and review of the literature.

We present a case of a female neonate with a cluster of six skin colored to yellowish pseudovesicular papules on her right forearm present since birth, initially thought to be a herpes simplex virus infection. Punch biopsy with immunostaining revealed a diagnosis of S100-negative, CD163-positive congenital cutaneous non-neural granular cell tumor. Only four other reports are presented in the literature of this entity, three of which also presented on the arm with somewhat similar clinical findings. We briefly reviewed the subtypes of classic and S100-negative non-neural granular cell tumors.

The Relationship Between Epidermal Mitotic Density, Atypical Mitotic Figure Density, Breslow Depth, Ulceration, and Dermal Mitotic Rate in Cutaneous Melanoma: A Retrospective Cohort Study.

Prognostic factors for melanoma include Breslow depth (BD), ulceration, and dermal mitotic rate (DMR). No studies have queried the effect of epidermal mitotic density (EMD) or atypical mitotic figure density (AMD) in an outcome-based assessment. Our objective was to determine if there is a relationship between EMD, AMD, BD, DMR, and ulceration and patient outcomes. This was a retrospective cohort study of 185 cases of thick and thin melanomas. Univariate and multivariate cause-specific regression analysis was performed. There was a positive correlation between EMD and BD (P = .0001). The difference between AMD in thick and thin melanomas was statistically significant. For every unit increase in EMD, patients had a 2.8-fold increase in the risk of distant metastasis; however, statistical significance was lost in the multivariate analysis. In adjusted analyses, ulceration, DMR, and BD were associated with outcomes. There were no statistically significant correlations between AMD and outcomes. This study is limited by its small sample size, diminution of the epidermis in some thick melanomas preventing EMD estimates, and reproducibility of mitotic figure counting. EMD and AMD do not seem to have any independent value in multivariate analyses for melanoma. Ulceration, BD, and DMR were significantly associated with outcomes and further solidify these known predictors of prognosis.

Cutaneous intralymphatic anaplastic lymphoma kinase-negative anaplastic large-cell lymphoma arising in a patient with multiple rounds of breast implants.

Primary cutaneous anaplastic large-cell lymphoma and breast implant-associated ALCL (BIA-ALCL) are rare subtypes of anaplastic lymphoma kinase (ALK)-negative ALCLs originating from skin and breast implants, respectively. Herein, we report a unique case of cutaneous ALK-negative ALCL occurring in the skin of left medial breast from a patient with multiple rounds of bilateral breast implants and a history of breast carcinoma. The lymphoma cells are entirely confined to the lymphatic channels in the dermis, and the patient has no other areas of skin abnormality, no lymphadenopathy, peri-implant fluid accumulation, or masses from the bilateral capsules of implants. The differential diagnosis and its relationship with breast implants are further explored.