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.

Diagnostic utility and comparative immunohistochemical analysis of MITF-1 and SOX10 to distinguish melanoma in situ and actinic keratosis: a clinicopathological and immunohistochemical study of 70 cases.

The histologic assessment of intraepidermal melanocytic proliferations involving sun-damaged skin may be challenging in scant biopsy material. Melanoma in situ may occasionally be confused with intraepidermal melanocytic hyperplasia on sun-damaged skin; thus, dermatopathologists may use immunohistochemical studies to help distinguish these entities. Historically, melanoma antigen recognized by T-cells 1 (MART-1) has been regarded as a valuable stain to confirm intraepidermal melanocytes; however, MART-1 may overestimate the number of melanocytes because it labels the melanoma dendrites and might also label pigmented keratinocytes, including structures mimicking junctional melanocytic nests in the setting of a lichenoid infiltrate. A total of 70 cases were retrospectively chosen, including 50 cases of melanoma in situ and 20 cases of actinic keratoses. SOX10 and microphthalmia transcription factor 1 (MITF-1) were performed in all cases. In all cases, the number of cells within epidermis that were identified as melanocytes by immunohistochemistry was compared with the number of melanocytes observed by morphology on hematoxylin and eosin sections. All cases of melanoma in situ showed expression of SOX10; however, the proportion of atypical melanocytes showing strong nuclear positivity was variable and did not approach that seen in MITF-1. There was no expression of either MITF-1 or SOX10 in adjacent pigmented keratinocytes in the cases of actinic keratoses. Both MITF-1 and SOX10 can be used to differentiate melanoma in situ from actinic keratosis with melanocytic hyperplasia; however, MITF-1 exhibits slight superior sensitivity and seems to be a more effective immunostain than SOX10 for the identification and quantification of melanocytes in the setting of melanoma in situ, especially in cases where there is limited tissue.

Atypical melanocytic lesions of the thigh with spitzoid and dysplastic features: a clinicopathologic study of 29 cases.

Melanocytic nevi in certain anatomic locations can display unusual histopathologic features potentially creating diagnostic uncertainty. Benign melanocytic nevi in sites such as acral, genital, and flexural areas may show unusual architecture and cytologic atypia, which can mimic dysplastic nevi and, sometimes, melanoma. Twenty-nine benign melanocytic skin lesions were identified in the thigh of 26 women and 3 men who showed atypical histologic features, including both dysplastic and spitzoid features. All lesions measured less than 1 cm in diameter. Eighteen cases showed features of compound nevi, and 11 were junctional. In all cases, the lesions displayed spitzoid features including large epithelioid and/or spindle cells, some melanocytes with ganglion-like cytomorphology, and focal suprabasilar upward migration. All cases showed dysplastic features. Clinical follow-up was available in 26 patients; no recurrences or metastases were observed. The demographic features and the anatomical sites of these melanocytic nevi appear to be reproducible, and in the assessment of histologically difficult cases, these data are helpful. It is our opinion that the malignant potential of these lesions with hybrid patterns (spitzoid/dysplastic) has yet to be determined, and although we favor these lesions to be benign, longer follow-up may yield a more complete understanding of their biologic potential.

Role of CD10, wide-spectrum keratin, p63, and podoplanin in the distinction of epithelioid and spindle cell tumors of the skin: an immunohistochemical study of 81 cases.

Cutaneous epithelioid and spindle cell neoplasms occasionally pose a significant diagnostic challenge on purely histologic grounds. Given the substantial clinicopathologic overlap between these lesions, especially in small biopsies, the use of immunohistochemical studies are essential. We evaluated the utility of a battery of immunohistochemical markers, including podoplanin (D2-40), CD10, p63, and wide-spectrum cytokeratin, for distinguishing cutaneous epithelioid and spindle cell tumors. A total of 81 cases, including 42 atypical fibroxanthoma (AFX), 13 spindle cell melanoma, 10 sarcomatoid carcinoma, 9 leiomyosarcoma (LMS), and 7 leiomyoma, formed the basis of our study. Immunohistochemical results were as follows-AFX: CD10 (35 of 42), p63 (1 of 42), CK (1 of 42), and podoplanin (19 of 42); spindle cell melanoma: CD10 (7 of 13), p63 (0 of 13), CK (0 of 13), and podoplanin (2 of 13); sarcomatoid carcinoma: CD10 (5 of 10), p63 (7 of 10), CK (4 of 10), and podoplanin (7 of 10); LMS: CD10 (4 of 9), p63 (0 of 9), CK (2 of 9), and podoplanin (1 of 9); and leiomyoma: CD10 (0 of 7), p63 (0 of 7), CK (0 of 7), and podoplanin (1 of 7). Our findings showed that the combination of certain immunohistochemical markers may be a useful adjunct in the evaluation of epithelioid and spindle cell tumors of the skin. In this study, we found that a combination of wide-spectrum cytokeratin and p63 are most helpful in the distinction of sarcomatoid carcinomas from other tumors; however, there remains a substantial minority of cases of sarcomatoid carcinoma that will consistently demonstrate negative staining for these markers. We also found that CD10 and podoplanin (D2-40) have limited diagnostic utility in epithelioid and spindle cell tumors of the skin; however, a strong and diffuse pattern of staining will favor the diagnosis of AFX. Caution should also be observed in the diagnosis of spindle cell malignant melanoma because some cases may express CD10, p63, and podoplanin while being nonreactive to S100 protein. Awareness of the limitations of the use of these stains and familiarity with their staining patterns in spindle and epithelioid cell tumors of the skin are extremely important because the prognostic and therapeutic implications for such neoplasms may be quite different.

The histomorphologic spectrum of primary cutaneous diffuse large B-cell lymphoma: a study of 79 cases.

Primary cutaneous large B-cell lymphomas (PCLBCL) have historically been a matter of debate in the literature. The 2005 World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification scheme segregated cutaneous B-cell lymphomas into 3 groups: primary cutaneous marginal zone B-cell lymphoma, primary cutaneous follicle center cell lymphoma, and primary cutaneous diffuse large B-cell lymphoma (PCDLBCL), "leg type" (PCDLBCL-LT). Additionally, the WHO-EORTC classification scheme utilized the term PCLBCL "other" not otherwise specified (NOS) type for rare cases of PCLBCL not belonging to either the "leg type" or the primary cutaneous follicle center cell lymphoma group. In this study, we retrospectively assessed the histomorphologic features of 79 cases of PCDLBCLs, including those of "leg type" and "other" NOS type, to further categorize the histologic spectrum of these unusual cutaneous neoplasms. The histologic diagnosis of PCLBCL usually poses little diagnostic difficulty; however, some cases may adopt unusual or unfamiliar appearances mimicking other lymphoproliferative disorders or other malignant neoplasms. Seventy-nine cases, occurring in 37 men and 42 women, aged 34-94 years, were analyzed. Fifty-three cases were classified as "leg type" and 26 cases were classified as "other" NOS type using the WHO-EORTC classification. Of the 53 cases classified as "leg type," 33 were women and 20 were men; of the 26 cases of "other" NOS type, 9 were women and 17 were men. In the "leg type" category, 31 cases were located on the lower extremities, 5 cases on the face, 5 cases on the arm, 3 cases on the chest, 2 cases on the shoulder, 2 cases on the back, 1 case on the trunk, 1 case on the buttock, 1 case on the supraclavicular area, 1 case on the head, and 1 case on the flank. Of the "other" NOS type category, 8 cases were located on the face, 5 cases on the shoulder, 3 cases on the head, 2 cases on the abdomen, 2 cases on the chest, 1 case on the trunk, 1 on the vulva, 1 on the axilla, 1 on the back, 1 on the neck, and 1 on the hip. Most cases assessed showed the classic morphologic appearance of PCDLBCL, but cases mimicking Burkitt lymphoma (starry-sky pattern), natural killer-cell (NK) lymphoma, mycosis fungoides (epidermotropism), low-grade B-cell lymphomas, epithelial malignancies, and Merkel cell carcinoma were encountered in this series. The high frequency of these rare histologic patterns can be explained by a bias associated with consultation practice. Careful histologic examination and immunohistochemical stains were used to establish the correct diagnosis. The differential diagnosis of PCDLBCL is broad and difficult to define histologically. Knowledge of these rare histologic variants is necessary to avoid misinterpretation of these cases as nonlymphoid malignancies.

Clinicopathologic analysis of the impact of CD23 expression in plasma cell myeloma with t(11;14)(q13;q32).

A recent study has shown that 10% of plasma cell myelomas (PCMs) express CD23 and that expression is associated with abnormalities of chromosome 11, mainly t(11;14)(q13;q32); however, only 40% of t(11;14)(+) PCMs express CD23. Because these results were generated in a limited patient cohort and because the clinical relevance of CD23 expression in PCMs with t(11;14)(q13;q32) has not been fully characterized, we addressed this question in a large series of patients with t(11;14)(+) PCM. Forty-two bone marrow biopsies from patients with t(11;14)(+) PCM were evaluated for CD23 expression by immunohistochemistry. CD23 expression was correlated with laboratory and clinical data and outcome after autologous stem cell transplantation, including event-free survival and overall survival (OS). Plasma cell myelomas with t(11;14)(q13;q32) were frequently CD20(+) (46.4%) and CD56(-) (53.8%) and had a nonhyperdiploid karyotype (97.6%) with frequent 13q deletion (33.3%). Of 42 cases, 19 (45.2%) expressed CD23. CD23(+) PCMs were more likely to present with platelet counts less than 150 × 10(3)/µL (100% vs 50%, P = .006). There were no significant differences in other laboratory or presenting clinical data. The median event-free survival in patients treated with autologous stem cell transplantation (n = 29) was similar regardless of CD23 status, whereas the median OS (all patients) was longer in CD23(-) than in CD23(+) PCMs: not reached vs 3365 days (P = .08). Our findings suggest that patients with t(11;14)(+)/CD23(+) PCM present with lower platelet counts and may have a shorter OS than those with t(11;14)(+)/CD23(-) PCM.

20-HETE increases survival and decreases apoptosis in pulmonary arteries and pulmonary artery endothelial cells.

20-Hydroxyeicosatetraenoic acid (20-HETE) is an endogenous cytochrome P-450 product present in vascular smooth muscle and uniquely located in the vascular endothelium of pulmonary arteries (PAs). 20-HETE enhances reactive oxygen species (ROS) production of bovine PA endothelial cells (BPAECs) in an NADPH oxidase-dependent manner and is postulated to promote angiogenesis via activation of this pathway in systemic vascular beds. We tested the capacity of 20-HETE or a stable analog of this compound, 20-hydroxy-eicosa-5(Z),14(Z)-dienoic acid, to enhance survival and protect against apoptosis in BPAECs stressed with serum starvation. 20-HETE produced a concentration-dependent increase in numbers of starved BPAECs and increased 5-bromo-2'-deoxyuridine incorporation. Caspase-3 activity, nuclear fragmentation studies, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays supported protection from apoptosis and enhanced survival of starved BPAECs treated with a single application of 20-HETE. Protection from apoptosis depended on intact NADPH oxidase, phosphatidylinositol 3 (PI3)-kinase, and ROS production. 20-HETE-stimulated ROS generation by BPAECs was blocked by inhibition of PI3-kinase or Akt activity. These data suggest 20-HETE-associated protection from apoptosis in BPAECs required activation of PI3-kinase and Akt and generation of ROS. 20-HETE also protected against apoptosis in BPAECs stressed by lipopolysaccharide, and in mouse PAs exposed to hypoxia reoxygenation ex vivo. In summary, 20-HETE may afford a survival advantage to BPAECs through activation of prosurvival PI3-kinase and Akt pathways, NADPH oxidase activation, and NADPH oxidase-derived superoxide.