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Cynthia Magro

Publications and source records attributed to Cynthia Magro.

At least 19 recordsLinked to original sources
PubMed2006

Promising pharmacologic innovations in treating pulmonary fibrosis.

Idiopathic pulmonary fibrosis is the most common form of the interstitial lung diseases and is characterized by chronic progressive pulmonary parenchymal fibrosis. Although the diagnosis and pathophysiology of this disease have been better characterized over the past few years, there remains no effective therapy for this disease. Therapies initially aimed at inflammation have proven ineffective, and newer strategies targeting aspects of aberrant wound repair involving alveolar epithelial cells or septal endothelial cells are now being investigated. Therapeutic strategies include the anti-fibrotic agents pirfenidone and interferon-gamma. Agents targeting specific cytokines, including connective tissue growth factor, transforming growth factor-beta and chemokines, are being evaluated. The restoration of oxidant balance and inhibition of leukotrienes represent other strategies. Additionally, the role of the coagulation/fibrinolytic systems and angiogenesis has also been examined.

Angiogenesis Inhibitors↗
PubMed2006

Natural killer cells produce T cell-recruiting chemokines in response to antibody-coated tumor cells.

In the current report, we have examined the ability of natural killer (NK) cells to produce T cell-recruiting chemokines following dual stimulation with interleukin (IL)-2 or IL-12 and human breast cancer cells coated with an antitumor antibody (trastuzumab). NK cells stimulated in this manner secreted an array of T cell-recruiting chemotactic factors, including IL-8, macrophage-derived chemokine, macrophage inflammatory protein 1alpha (MIP-1alpha), monocyte chemoattractant protein 1, and regulated on activation, normal T-cell expressed and secreted (RANTES), whereas stimulation of NK cells with either agent alone had minimal effect. Furthermore, these factors were functional for T-cell chemotaxis as culture supernatants derived from costimulated NK cells induced migration of both naïve and activated T cells in an in vitro chemotaxis assay. T-cell migration was significantly reduced when neutralizing antibodies to IL-8, MIP-1alpha, or RANTES were added to culture supernatants before their use in the chemotaxis assay. In addition, coadministration of trastuzumab-coated tumor cells and IL-12 to mice led to enhanced serum MIP-1alpha. As a clinical correlate, we examined the chemokine content of serum samples from breast cancer patients enrolled on a phase I trial of trastuzumab and IL-12, and found elevated levels of IL-8, RANTES, IFN-gamma inducible protein 10, monokine induced by IFN-gamma, and MIP-1alpha, specifically in those patients that experienced a clinical benefit. Sera from these patients exhibited the ability to direct T-cell migration in a chemotaxis assay, and neutralization of chemokines abrogated this effect. These data are the first to show chemokine production by NK cells, specifically in response to stimulation with antibody-coated tumor cells, and suggest a potential role for NK cell-derived chemokines in patients receiving therapeutic monoclonal antibodies.

Adenocarcinoma↗
PubMed2006

Incorporation of photodynamic therapy as an induction modality in non-small cell lung cancer.

BACKGROUND AND OBJECTIVES: Incorporation of photodynamic therapy (PDT) into the induction therapy regimen utilized for treatment of locally advanced primary non-small cell bronchogenic carcinoma (NSCLC) is explored. STUDY DESIGN/MATERIALS AND METHODS: We present a retrospective review of 41 patients diagnosed with non-metastatic NSCLC who underwent induction PDT with chemotherapy and/or radiation. RESULTS: Fifty percent of patients initially deemed unresectable, were able to undergo definitive surgical resection after trimodality induction therapy. Twenty-seven percent of patients considered to require pneumonectomy were able to have a lobectomy. The pathological stage was less than the preinduction clinical stage in 14 of 22 cases; of which four patients had no residual tumor. There was no 30/90-day postoperative mortality. Mean survival was 35.9 months (lobectomy), 25.5 months (pneumonectomy) and 14.7 months (no surgery). Median survival was 78% (12 months) and 46% (36 months). The main postoperative complication following pneumonectomy was bronchopleural fistula formation. All patients who developed this complication had undergone trimodality induction therapy. Incorporation of PDT into the induction arsenal for patients with loco-regionally advanced NSCLC may be safely performed. CONCLUSIONS: PDT may define an alternative induction strategy for patients requiring pneumonectomy; further studies exploring the true efficacy of PDT as an induction modality are encouraged.

Adult↗
PubMed2006

Unusual histologic and clinical variants of melanoma: implications for therapy.

Unusual histologic variants of melanoma may prove problematic to the histopathologist. Several of these variants are sufficiently rare that their biological behavior remains obscure. Because identification of some of these melanoma subtypes has specific implications for the therapeutic approach and some may mimic other forms of epithelial or mesenchymal neoplasia, their recognition is key to patient management.

Diagnosis, Differential↗
PubMed2005

Expression of STAT1 and STAT2 in malignant melanoma does not correlate with response to interferon-alpha adjuvant therapy.

Interferon-alpha (IFN-alpha) is used as an adjuvant therapy in patients with malignant melanoma and who have undergone surgical resection of high-risk lesions. Defective expression or activation of STAT1 or STAT2 has been shown to correlate with IFN-alpha or resistance in vitro; however, recent data from our laboratory suggest that the anti-tumor effects of IFN-alpha are dependent on STAT1 signaling within host immune cells. We measured STAT1 and STAT2 expression in 28 melanoma biopsies (8 cutaneous lesions; 1 lung metastasis; 19 nodal metastases) obtained from patients prior to the initiation of adjuvant IFN-alpha therapy. Disease recurrence following IFN-alpha treatment did not correlate with the staining intensity of either STAT1 (P = 0.61) or STAT2 (P = 0.52). Tumors with minimal STAT1 or STAT2 expression (< 20% positive) were present in four patients with tumor-positive lymph nodes, who exhibited prolonged relapse-free survival (> 44 months) following adjuvant therapy. Conversely, high levels of STAT1 were present in a patient who recurred during the course of IFN-alpha therapy. A case study of one patient who experienced recurrent disease during IFN-alpha treatment revealed that STAT1 levels were greater in the recurrent tumor when compared to the original lesion. These studies provide direct evidence to suggest that levels of STAT1 and STAT2 within the tumor do not influence a patient's response to adjuvant IFN-alpha.

Adult↗
PubMed2005

Cytomegalovirus-associated pulmonary septal capillary injury sine inclusion body change: a distinctive cause of occult or macroscopic pulmonary hemorrhage in the immunocompetent host.

The authors describe four patients with symptomatic lung disease morphologically representing a septal capillary injury syndrome temporally associated with serologic and culture evidence of active cytomegalovirus (CMV) infection but without classic cytopathic changes. The authors conducted a thorough review of clinical data, microscopic examination, and in situ hybridization to detect CMV mRNA encoding immediate early protein. The assay detects transcripts that encode early and immediate early proteins. In two cases additional tissue was available for direct immunofluorescent studies. The disease process in each of the patients was morphologically indistinguishable from the pattern of organ injury associated with autoimmune diseases including a small vessel microvascular injury syndrome involving skin and lung and immune complex- mediated glomerulonephritis. Cytopenias were seen in all cases, most commonly thrombocytopenia. All treated patients demonstrated improvement on combined ganciclovir and low-dose steroid therapy. CMV infection may be of pathogenetic importance in some cases of alveolar hemorrhage, especially when accompanied by peripheral blood cytopenia in otherwise healthy patients and if clinical worsening occurs in the setting of a traditional immunosuppressive regimen typically used to treat vasculitis.

Capillaries↗
PubMed2004

The antitumor effects of interferon-alpha are maintained in mice challenged with a STAT1-deficient murine melanoma cell line.

INTRODUCTION: Interferon-alpha (IFN-alpha) is currently administered to patients with metastatic malignant melanoma and those who are at risk for recurrence following surgery for high-risk lesions. Signal transducer and activator of transcription 1 (STAT1) is a transcription factor that is activated by IFN-alpha and is thought to mediate the majority of its antitumor effects. Loss of STAT1 has been found in IFN-resistant melanoma cells. We developed a murine melanoma cell line in a STAT1-deficient mouse. We also transfected B16 melanoma cells with a wild-type form of STAT1 to induce its overexpression. Using the resulting cell lines and STAT1-deficient mice, we tested whether IFN-alpha could exert an antitumor effect on melanoma cells in the absence of STAT1-mediated signal transduction. MATERIALS AND METHODS: A melanoma tumor was induced in STAT1-deficient mice via the application of DMBA (tumor initiator) followed by croton oil (tumor promoter). Immunohistochemical analysis confirmed that the resulting tumor was a malignant melanoma. Immunoblot analysis, intracellular flow cytometry, and gel-shift analysis were used to confirm the lack of STAT1 in the derivative cell line (AGS-1). In addition, the STAT1 protein was overexpressed in B16 melanoma cells by stable transfection with a plasmid construct encoding wild-type STAT1. The effects of IFN-alpha on these cell lines were studied in vitro and in vivo. RESULTS: STAT1 was not expressed in the AGS-1 murine melanoma cell line. Treatment with IFN-alpha did not lead to activation of STAT1. Cell proliferation assays revealed that while IFN-alpha did not exert an antiproliferative effect on this cell line, it was capable of prolonging the survival of STAT1-competent C57BL/6 mice bearing 1 x 10(6) AGS-1 tumor cells in the intraperitoneal position (n = 20, P < 0.05), as compared to PBS-treated controls. Also, the survival of IFN-alpha-treated mice (as compared to PBS-treated controls) was not affected by the overexpression of STAT1 in B16 tumor cells. CONCLUSIONS: This data suggests that IFN-alpha can enhance survival in an animal model where STAT1-mediated signal transduction and gene regulation is absent within the tumor but is present within the host. This data also indicates that the overexpression of STAT1 within the tumor does not significantly enhance the effects of exogenously administered IFN-alpha in this model. These findings indicate that the bulk of the antitumor actions of IFN-alpha may be derived from its effects on host tissues.

Animals↗
PubMed2004

Assessment of T-cell clonality via T-cell receptor-gamma rearrangements in cutaneous T-cell-dominant infiltrates using polymerase chain reaction and single-stranded DNA conformational polymorphism assay.

Discerning the pathologic significance of cutaneous T-cell infiltrates can pose a diagnostic challenge for dermatopathologists. Reactive conditions such as drug-associated lymphomatoid hypersensitivity and lymphomatoid lupus erythematosus can demonstrate lymphoid atypia and a phenotype resembling cutaneous T-cell lymphoma (CTCL). Further, lymphoid dyscrasias such as pityriasis lichenoides chronica, large plaque parapsoriasis, and atypical pigmentary purpura confuse the picture because they not only mimic CTCL but also represent prelymphomatous states with inherent malignant potential. Although the emergence of a dominant clone has been considered a clue indicative of a T-cell dyscrasia, there are reports concerning the identification of monoclonality in biopsies of reactive lymphoid infiltrates. We have conducted a modified single-stranded DNA conformational polymorphism (SSCP) assay using paraffin-embedded, formalin-fixed tissue on 92 T-cell-rich biopsies to determine the relative specificity and sensitivity of this methodology. In addition, laser capture microdissection (LCM) was performed on 22 of the 92 samples to isolate the area of interest and to compare its specificity and sensitivity with those SSCP assays performed without LCM. We found that monoclonality or oligoclonality is 86% specific for preneoplastic and neoplastic states, whereas the finding of polyclonality appears to be relatively specific for a reactive process. Some cases of reversible T-cell dyscrasia produced a molecular profile mimicking lymphoma or prelymphomatous states by virtue of monoclonality or oligoclonality. Although LCM appears to improve the sensitivity for detecting preneoplastic conditions, the relative specificity appears to be the same as that encountered with routine SSCP.

Clone Cells↗
PubMed2003

Cutaneous manifestations of Crohn's disease, its spectrum, and its pathogenesis: intracellular consensus bacterial 16S rRNA is associated with the gastrointestinal but not the cutaneous manifestations of Crohn's disease.

The classic pathology of skin disease discontinuous from the inflamed gastrointestinal (GI) tract in patients with Crohn's disease (CD) includes pyoderma gangrenosum (PG), erythema nodosum (EN), and so-called metastatic Crohn's disease. The purpose of this study was two-fold: First, we explored the full spectrum of cutaneous lesions associated with Crohn's disease, and second, we sought to explore a potential molecular basis of the skin lesions in patients with CD. In this regard, we analyzed skin and GI tract biopsies from affected patients for the consensus bacterial SrRNA to determine whether direct bacterial infection was associated with either condition. Formalin-fixed, paraffin-embedded sections were studied and correlated to clinical presentation and histories from 33 patients with CD. Consensus bacterial RNA sequences were analyzed using an RT in situ PCR assay on both skin biopsy and GI biopsy material. The GI tract material included biopsies from 3 patients who had skin lesions and from 7 patients in whom there were no known skin manifestations. There were 8 cases of neutrophilic dominant dermal infiltrates, including pyoderma gangrenosum, 6 cases of granuloma annulare/necrobiosis lipoidica-like lesions, 5 cases of sterile neutrophilic folliculitis, 5 cases of panniculitis, 4 cases of vasculitis, 2 cases of psoriasis, 2 cases of lichenoid and granulomatous inflammation, and 1 case of classic metastatic CD. Intracellular bacterial 16S rRNA was detected in 8 of 10 tissues of active CD in the GI tract, of which 3 of the cases tested were from patients who also developed skin lesions at some point in their clinical course; in contrast, none of the skin biopsies had detectable bacterial RNA. The dermatopathological manifestations of CD discontiguous from the involved GI tract mucosa have in common a vascular injury syndrome, typically with a prominent extravascular neutrophilic and/or histiocytic dermal infiltrate. In addition, this study, the first to document in situ intracellular consensus bacterial SrRNA in the GI tract in CD, suggests that hematogenous dissemination of viable microbes is not associated with the cutaneous manifestations of this disease. Bacteria do, however, appear to play a role in bowel lesions of patients with CD.

Adolescent↗
PubMed2003

Pyoderma gangrenosum: a review.

Since its first description in 1930, the pathogenesis of pyoderma gangrenosum (PG) has remained obscure even as an ever-widening array of systemic diseases has been described in association with it. The histopathologic distinction of PG from other ulcerative processes with dermal neutrophilia is challenging and at times impossible. In consequence, when confronted with a biopsy from such a lesion, the pathologist has an obligation to obtain a full and detailed clinical history. In short, as a diagnosis of PG does not hinge exclusively upon the biopsy findings in isolation from other studies, a solid knowledge of the clinical features, the systemic disease associations and the differential diagnosis will help the pathologist to avoid diagnostic pitfalls or the generation of a report which is non-contributory to patient care. In this review, we describe in detail the different clinicopathologic forms of PG, summarize the diseases associated with this process in the literature and in our experience, and briefly review the treatment options.

Adult↗
PubMed2003

Automated kappa and lambda light chain mRNA expression for the assessment of B-cell clonality in cutaneous B-cell infiltrates: its utility and diagnostic application.

INTRODUCTION: Primary cutaneous B-cell lymphoma (1 degrees CBCL) accounts for 25% of all lymphomas. The difficulty in distinction of reactive from neoplastic B-cell infiltrates prompts the use of molecular diagnostic adjuncts. While T-cell clonality can be seen in various reactive states, clonal B-cell infiltrates are often neoplastic; standard assays employed include polymerase chain reaction (PCR) or Southern blot analysis to assess heavy chain rearrangement. We sought to assess the utility of kappa (kappa) and lambda (lambda) mRNA expression using the Ventana automated assay (Ventana Medical Systems, Tucson, AZ, USA) in the analysis of atypical cutaneous B-cell lymphoid infiltrates. MATERIALS AND METHODS: Multiple 4 micro m sections of paraffin-embedded, formalin-fixed skin biopsies from 31 patients with CBCL were placed on silane-coated slides, deparaffinized, then digested in pepsin (5 mg/ml) for 30 min at 37 degrees C. Fluorescein-tagged oligoprobes and tissue mRNA were denatured at 80 degrees C for 5 min, hybridized for 2 h at 37 degrees C, and incubated with antifluorescein alkaline phosphatase conjugates. Detection of the probe target complex employed nitroblue tetrazolium and bromochloroindolyl phosphate conjugates with a nuclear fast red counterstain. A kappa : lambda ratio > 3 : 1 was held to represent kappa light chain restriction and a kappa : lambda ratio </= 1 : 1 to indicate lambda light chain restriction. RESULTS: The diagnosis in each case was determined by careful integration of clinical, histologic, and phenotypic data. The diagnoses included: pseudolymphoma (PL), marginal zone lymphoma (MZL), 1 degrees CBCL of the trunk, scalp or leg, 2 degrees lymphoma, and plasma cell dyscrasia. All but one case of lymphoma were light chain restricted. All cases of PL were proven to be polyclonal by this methodology. In non-plasmacytic small cell lymphomas, only 5-10% of the infiltrate expressed kappa or lambda, with clonality established through the abnormal kappa : lambda ratio. Interpretations were most difficult in the 2 degrees small cell-dominant follicular center cell lymphomas and easiest in cases with significant plasmacytic differentiation (i.e. MZL, immunocytomas, or plasma cell dyscrasias). CONCLUSION: The Ventana kappa/lambda assay is a reliable, quick, and inexpensive way to determine B-cell clonality in cutaneous lymphoid infiltrates in paraffin-embedded formalin-fixed tissue.

B-Lymphocytes↗
PubMed2003

Mammographic findings in pseudoxanthoma elasticum.

BACKGROUND: There have been isolated case reports of arterial and skin calcification in mammograms of patients with pseudoxanthoma elasticum (PXE), and unpublished anecdotes of many women with PXE undergoing breast biopsy for evaluation of microcalcifications. OBJECTIVE: Our aim was to systematically evaluate mammography and breast pathology in PXE. METHODS: The mammograms of 51 women with confirmed PXE were compared with those of a control sample of 109 women without PXE, noting each of the following characteristics on each mammogram: breast density, skin thickening, skin microcalcifications, vascular calcification, breast microcalcifications and macrocalcifications, and masses. The characteristics of the 2 samples were compared using the 2-tailed t test with a pooled estimate of variance. The indications for mammography and data for each of the mammographic findings were analyzed using the chi(2) test. Available breast biopsy material was reviewed. RESULTS: The PXE and control groups were similar in age and indications for mammography. There was a statistically significant increase in skin thickening, vascular calcification, and breast microcalcifications in the PXE group (P <.001 each). Breast density, masses, macrocalcifications, and skin calcification did not differ statistically in the 2 groups, but no control patient had axillary calcification, or both vascular calcification and microcalcifications (P <.001). Nearly 1 in 7 of the patients with PXE demonstrated at least 3 of the following: microcalcifications, skin calcifications, vascular calcification, and skin thickening; whereas none of the control group did. Histopathologic findings of breast tissue showed calcification of dermal elastic fibers, subcutaneous arteries, and elastic fibers of the deep fascia and interlobular septae of the fat adjacent to breast parenchyma. CONCLUSION: Breast microcalcification and arterial calcification are not rare in the normal population and are not of diagnostic value. The presence of both of these findings, especially with skin thickening or axillary skin calcification, should suggest a diagnosis of PXE. The majority of breast calcifications in PXE are benign.

Adult↗
PubMed2003

Recent developments in the biology and therapy of T-cell and natural killer-cell lymphomas.

PURPOSE OF REVIEW: T-cell/natural killer (T/NK)-cell lymphomas represent a group of poor-risk lymphoproliferative disorders that have only recently been recognized as distinct clinicopathologic entities. The average outcome with currently available therapy is substantially inferior to that of aggressive B-cell lymphomas. Significant gaps remain in our knowledge of their origin, diagnosis, and clinical spectrum. This review outlines recent developments in the biology and molecular genetics of these disorders, current diagnostic challenges, and future avenues for therapy. RECENT FINDINGS: Several cancer-prone transgenic mouse models that develop predominantly T/NK-cell lymphomas have been produced in the past 2 to 3 years. These models point to an important role for chronic cytokine stimulation and for disruption of genes involved in the control of chromatin remodeling and maintenance of genome integrity in the pathogenesis of T-cell lymphomas. The recognition of T/NK-cell lymphomas has been greatly facilitated by the broad acceptance of standard diagnostic criteria and by the increasing availability of assays for the analysis of T-cell receptor rearrangement and a more precise definition of functional T/NK-cell subsets. New drugs with potential for use in T/NK-cell lymphomas, including monoclonal antibodies, tyrosine kinase inhibitors, synthetic retinoids, immunoconjugates, and immunosuppressive molecules with novel mechanisms of action are in the early phase of clinical investigation. SUMMARY: Much remains to be learned in the pathogenesis, clinical spectrum, and optimal therapy of T/NK-cell lymphomas. The availability of animal models of disease, new diagnostic tools, and targeted drugs with novel mechanisms of action should lead to rapid progress in this group of malignancies in the near future.

Animals↗
PubMed2003

Rapid diagnosis of smallpox infection and differentiation from its mimics.

The potential for a bioterrorism-induced smallpox outbreak has been much discussed of late. The literature of the late 1960s stressed that the distinction between smallpox and the other viral-induced vesicle-forming diseases, namely varicella zoster and disseminated herpes simplex, was difficult to make. Given that the cutaneous manifestations of smallpox would be among the initial symptoms, we reviewed 2 cases of smallpox diagnosed in South America in the 1970s in conjunction with 9 cases of multiple skin vesicles diagnosed as either disseminated herpes simplex or varicella-zoster. These were examined by routine hematoxylin and eosin stain (H&E) as well as by in situ hybridization. A blind review of the cases demonstrated that each showed striking intraepithelial vesicles containing multinucleated squamous cells exhibiting a ground glass appearance of the nuclear chromatin. Thus, as expected, routine H&E examination could not differentiate the 2 smallpox cases from the other 9 samples. In situ hybridization easily distinguished the 2 cases of smallpox from the other 9 samples, 5 of which contained varicella-zoster (two had been misdiagnosed as herpes) and the other 4 were disseminated herpes simplex. The in situ test, readily accomplished in any histology-based molecular laboratory in 4 hours, allows for the rapid and specific identification of smallpox infection and, importantly, its distinction from its mimics. Formalin fixation, which is optimal for in situ hybridization, guarantees the inactivation of the smallpox virus.

Bioterrorism↗
PubMed2003

The antitumor effects of IFN-alpha are abrogated in a STAT1-deficient mouse.

IFN-alpha activates the signal transducer and activator of transcription (STAT) family of proteins; however, it is unknown whether IFN-alpha exerts its antitumor actions primarily through a direct effect on malignant cells or by stimulating the immune system. To investigate the contribution of STAT1 signaling within the tumor, we generated a STAT1-deficient melanoma cell line, AGS-1. We reconstituted STAT1 into AGS-1 cells by retroviral gene transfer. The resulting cell line (AGS-1STAT1) showed normal regulation of IFN-alpha-stimulated genes (e.g., H2k, ISG-54) as compared with AGS-1 cells infected with the empty vector (AGS-1MSCV). However, mice challenged with the AGS-1, AGS-1STAT1, and AGS-1MSCV cell lines exhibited nearly identical survival in response to IFN-alpha treatment, indicating that restored STAT1 signaling within the tumor did not augment the antitumor activity of IFN-alpha. In contrast, STAT1-/- mice could not utilize exogenous IFN-alpha to inhibit the growth of STAT1+/+ melanoma cells in either an intraperitoneal tumor model or in the adjuvant setting. The survival of tumor-bearing STAT1-/- mice was identical regardless of treatment (IFN-alpha or PBS). Additional cell depletion studies demonstrated that NK cells mediated the antitumor effects of IFN-alpha. Thus, STAT1-mediated gene regulation within immune effectors was necessary for mediating the antitumor effects of IFN-alpha in this experimental system.

Animals↗
PubMed2003

Granulomatous eccrinotropic lymphomatoid papulosis.

We describe 9 patients with a novel variant of lymphomatoid papulosis characterized by prominent localization of the infiltrate around the eccrine coil, resulting in nodular expansion of the coil accompanied by variable granulomatous inflammation. Light microscopy, immunohistochemical analysis using antibodies to CD2, CD3, CD4, CD5, CD7, CD8, and CD30 in 6 cases, and polymerase chain reaction--single-stranded conformational polymorphism analysis for T-cell receptor gamma chain gene rearrangement in 5 cases revealed 2 cytomorphologic patterns (large cell dominant with polymorphous inflammation, small cell lymphocyte--rich with an inconspicuous large cell component [phenotypes, CD30+/CD3+/CD4+/CD7-for large atypical cells; reactive for small lymphocytes]) and clonal restriction in 4 and polyclonality in 1 of the lymphocyte-dominant cases. During an average 6-year follow-up, no lymphomas developed. Recognition of this variant is important--accentuation of the infiltrate around the eccrine coil and cutaneous nerves, presence of granulomatous inflammation, dominance of small lymphocytes in the dermis, and variable extension into the panniculus may lead to diagnostic confusion with entities such as discoid lupus erythematosus, Jessner lymphocytic infiltrate of skin, subcutaneous T-cell lymphoma, and persistent arthropod bite reaction. Our findings suggest that pruritus, a younger age at diagnosis, and a more indolent course are defining clinical features.

Adult↗
PubMed2003

The histopathologic spectrum of cryofibrinogenemia in four anatomic sites. Skin, lung, muscle, and kidney.

Although the histologic characteristics of cryofibrinogenemia have been described in skin lesions, the literature is largely devoid of descriptions of this disorder in other organs. This series is the first to document the histopathologic manifestations of intrapulmonary, intramuscular, and renal cryofibrinogenemia. We describe the histopathologic manifestations of cryofibrinogenemia in 10 cases with manifestations in 4 organ systems: skin in 7 cases, skeletal muscle in 2, lung in 2, and kidney in 1. Irrespective of anatomic site, all lesions showed an occlusive thrombotic diathesis comprising eosinophilic refractile deposits within vessel lumina with extension into the intima, with or without an accompanying characteristic granulomatous vasculitic component. Ultrastructural examination of the renal deposits showed fibrillary material within glomerular capillary lumina with unique morphologic features not previously described. Analysis of plasma from several cases revealed a cold-precipitable protein, which in most cases included a monoclonal paraprotein. The laboratory and histologic distinctions between cryofibrinogenemia and cryoglobulinemia are addressed. We provide guidelines for the proper handling of patient specimens in the workup of cryofibrinogenemia.

Adult↗