Maria Yadira Hurley

State of the art in myeloid sarcoma

Introduction:  Myeloid sarcomas are extramedullary lesions composed of myeloid lineage blasts that typically form tumorous masses and may precede, follow, or occur in the absence of systemic acute myeloid leukemia. They most commonly involve the skin and soft tissues, lymph nodes, and gastrointestinal tract and are particularly challenging to diagnose in patients without an antecedent history of acute myeloid leukemia.

Mutations in the GGCX and ABCC6 Genes in a Family with Pseudoxanthoma Elasticum-Like Phenotypes

A characteristic feature of classic pseudoxanthoma elasticum (PXE), an autosomal recessive disorder caused by mutations in the ABCC6 gene, is aberrant mineralization of connective tissues, particularly the elastic fibers. Here, we report a family with PXE-like cutaneous features in association with multiple coagulation factor deficiency, an autosomal recessive disorder associated with GGCX mutations. The proband and her sister, both with severe skin findings with extensive mineralization, were compound heterozygotes for missense mutations in the GGCX gene, which were shown to result in reduced gamma-glutamyl carboxylase activity and in undercarboxylation of matrix gla protein. The probands mother and aunt, also manifesting with PXE-like skin changes, were heterozygous carriers of a missense mutation (p.V255M) in GGCX and a null mutation (p.R1141X) in the ABCC6 gene, suggesting digenic nature of their skin findings. Thus, reduced gamma-glutamyl carboxylase activity in individuals either compound heterozygous for a missense mutation in GGCX or with haploinsufficiency in GGCX in combination with heterozygosity for ABCC6 gene expression results in aberrant mineralization of skin leading to PXE-like phenotype. These findings expand the molecular basis of PXE-like phenotypes, and suggest a role for multiple genetic factors in pathologic tissue mineralization in general.

Use of classic and novel immunohistochemical markers in the diagnosis of cutaneous myeloid sarcoma

Cutaneous myeloid sarcoma is often challenging to diagnose based solely upon histopathological features. Although immunohistochemistry can aid in its diagnosis, specific markers have not been clearly identified. We evaluated the utility of immunohistochemical markers in 57 cutaneous myeloid sarcoma cases. In addition to classical markers (CD117, CD163, CD34, myeloperoxidase and lysozyme), we used CD33 and CD14, recently described markers in paraffin‐embedded tissue samples, and Kruppel‐like factor 4 (KLF‐4), a novel monocytic marker. Our results show that lysozyme was expressed in 91%, CD33 in 60%, myeloperoxidase in 54%, CD34 in 39% and CD117 in 36% of cases. An antibody panel that included lysozyme, CD117 and CD33 identified all cases. The monocytic markers CD14, KLF‐4 and CD163 were expressed in 60, 58 and 40% of all cases, respectively. CD14 and KLF‐4 expression was significantly more common in cases with monocytic differentiation. CD14 is the single most sensitive and specific marker for monocytic differentiation (79 and 80%). Although KLF‐4 in isolation is relatively insensitive (50 and 87%), it enhances sensitivity in detecting monocytic cutaneous myeloid sarcoma when combined with CD14. Our results indicate that in addition to classical immunohistochemical markers, targeted use of newer antibodies, including CD33, CD14 and KLF‐4 is useful in the diagnosis of cutaneous myeloid sarcoma and in the detection of monocytic differentiation.

Immunohistochemical differentiation of four benign eccrine tumors

Background:  The histogenesis and differentiation of eccrine tumors, including cylindroma, poroma, spiradenoma and syringoma, remains controversial. This controversy may be because of sporadic and incomplete studies of these neoplasms.

Psoriasis in the Geriatric Population

This article provides an overview of the diagnosis, epidemiology, and management of psoriasis, with a focus on the special characteristics of managing elderly patients. Complications particular to psoriasis patients and the side effects of treatment options are described.

Appropriate use criteria in dermatopathology: Initial recommendations from the American Society of Dermatopathology

Appropriate use criteria (AUC) provide physicians guidance in test selection, and can affect health care delivery, reimbursement policy and physician decision‐making.

Review of the medical literature and assessment of current utilization patterns regarding the use of two common fluorescence in situ hybridization assays in the diagnosis of dermatofibrosarcoma protuberans and clear cell sarcoma

Dermatofibrosarcoma protuberans (DFSP) is a tumor of intermediate malignancy, which in selected circumstances can pose difficulty in diagnosis. Clear cell sarcoma (CCS) is a very rare aggressive soft tissue sarcoma that can be difficult to distinguish histologically from melanoma.

Primary cutaneous perivascular epithelioid cell tumor (PEComa): Five new cases and review of the literature

PEComas represent a family of uncommon mesenchymal tumors composed of “perivascular epithelioid cells” with a distinct immunophenotype that typically shows both myogenic and melanocytic differentiation. The PEComa family includes angiomyolipoma (AML), clear cell “sugar” tumor of the lung and extra pulmonary sites, lymphangioleiomyomatosis and clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres. Very rarely, PEComas may arise in the skin. Primary cutaneous PEComas typically display a dermal proliferation of epithelioid cells with pale, clear, or granular pink cytoplasm arranged in nests and trabecula with an intervening arborizing network of delicate capillaries. Primary cutaneous PEComas have a lower frequency of myogenic marker expression than their deep soft tissue and visceral counterparts. They also often express strong diffuse CD10, leading to potential confusion with metastatic renal cell carcinoma. Most cases behave indolently. We report 5 additional cases of this rare entity. All showed classic histologic features and expression of either HMB‐45 and/or Melan‐A/MART‐1. Four cases were tested for myogenic markers (2 were positive & 2 were negative). Three cases were tested for CD10 (all 3 were positive). All of our cases with clinical follow‐up behaved indolently. Table 1 provides a summary of findings for all 5 cases in our series.

p53 Is a Helpful Marker in Distinguishing Langerhans Cell Histiocytosis From Langerhans Cell Hyperplasia.

Abstract: Langerhans cell histiocytosis (LCH) is a proliferative disorder of Langerhans cells that can be challenging to distinguish histologically from Langerhans cell (LC) hyperplasia, seen in a variety of inflammatory dermatoses. Lesional cells in both entities demonstrate positive staining for CD1a and S100. Previous studies have demonstrated positive staining of fascin, CD31, and p53 in cases of LCH, but currently, no studies have compared the staining profiles of these markers between LCH and LC hyperplasia. The authors compared immunohistochemical staining profiles of LCH (n = 15) and various inflammatory dermatoses with LC hyperplasia (n = 15) using fascin, CD31, and p53. Fascin, CD31, and p53 were graded as a percentage of CD1a staining cells in the epidermis and dermis of each specimen. Fascin showed no significant differences in staining between the 2 entities. CD31 was positive in the dermal infiltrate in 40% of cases of LCH and negative in all cases of LC hyperplasia. p53 was positive in the epidermal infiltrate in 50% of cases of LCH, and positive in the dermal infiltrate in 93% of cases of LCH, whereas negative in all cases of LC hyperplasia. Fascin was not a helpful marker in distinguishing LCH from LC hyperplasia. CD31, if positive in the dermal infiltrate, is suggestive of a diagnosis of LCH, but exhibits a relatively low sensitivity for this purpose. p53 proved to be a helpful and accurate diagnostic immunohistochemical stain when distinguishing between LCH and LC hyperplasia.

Diagnosis and Management of Bullous Disease

As the population ages, the prevalence of bullous skin diseases will escalate. Efficient management depends on timely recognition by the physician and reduces the morbidity associated with the disease course. This article outlines the common bullous dermatoses affecting older adults and provides tips for a streamlined approach to workup and treatment.