Biomedical subjects

Cynthia M Magro

Publications and source records attributed to Cynthia M Magro.

At least 37 records · Page 2Linked to original sources

PubMed2006

Lipodermatosclerosis as a form of vascular compromise-associated radiation recall dermatitis: case report and a review of literature.

Lipodermatosclerosis (LDS) is a prototypic ischemic dermopathy that is most commonly associated with venous insufficiency. There have been no prior reports describing LDS as a form of radiation recall dermatitis (RRD). We present a case of a 47-year-old female affected by squamous cell carcinoma of the anus who underwent irradiation and subsequent chemotherapy with 5-fluorouracil and cisplatin. She then developed tender, erythematous, indurated plaques on skin of the buttocks, corresponding closely to one of the previous radiotherapy fields. As histopathological studies were compatible with LDS and the skin eruption coincided with drug intake 3 months after radiotherapy, the diagnosis of RRD with LDS features was rendered. This is the first case providing evidence of the causative role of 5-fluorouracil and cisplatin in potentially inducing RRD.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

Pediatric primary cutaneous marginal zone lymphoma: in association with chronic antihistamine use.

Primary cutaneous marginal zone lymphoma of the mucosa-associated lymphoid tissue predominantly occurs in adults and is rare in children. There have been no prior reports of this lymphoma occurring in American children. We present a case of a 15-year-old male with a history of atopic diathesis and chronic use of antihistamine agents who presented with an asymptomatic lesion on his left forearm of 6 months duration. Because histopathological and immunohistochemical studies were compatible with marginal zone lymphoma, and the patient had no associated extracutaneous disease, the diagnosis of primary cutaneous marginal zone lymphoma was rendered. Based on the patient's past medical history prior to appearance of lesion, it was postulated that the development of lymphoma was associated with the ingestion of antihistamines and further propagated by his underlying atopic diathesis.

Adolescent↗

PubMed2006

Primary CD20+CD10+CD8+ T-cell lymphoma of the skin with IgH and TCR beta gene rearrangement.

Most cutaneous T-cell lymphomas are derived from mature postthymic T cells of the CD4 subtype. When other less common profiles are encountered, a diagnostic challenge is posed. Accurate categorization is critical because of the specificity of therapeutic regimens, including biologics. A 65-year-old woman was seen in 2001 because of a thigh mass manifesting an unusual phenotype eventually categorized as a mature postthymic CD8+ T-cell lymphoma with CD10 and weak CD20 expression. Molecular studies revealed T-cell receptor and heavy chain immunoglobulin rearrangement. Her cutaneous disease progressed despite several cycles of chemotherapy and radiation therapy. However, a therapeutic trial with denileukin diftitox resulted in a striking response. The importance of this case lies in the novel phenotype and dual T- and B-cell rearrangements. Rather than representing an aberrant phenotype, this tumor may represent the malignant counterpart of a benign population of weakly CD20+ T cells of the CD8 subset.

Aged↗

PubMed2006

CD8+ lymphomatoid papulosis and its differential diagnosis.

We describe 5 cases (4 males, 14-43 years old; 1 female, 61 years old) of primary cutaneous T-cell lymphoproliferative lesions expressing a CD8/granzyme/CD30-positive phenotype. Four cases were compatible with lymphomatoid papulosis (LyP) based on the clinical course, which was recurrent asymptomatic papular nodular lesions over years responding to methotrexate; granulomatous inflammation and lack of other inflammatory cell elements were characteristic. In 1 case, an initial erroneous diagnosis was made of aggressive epidermotropic CD8+ T-cell lymphoma. The fifth case in this series was first interpreted as representing primary cutaneous anaplastic large cell lymphoma but was later recategorized as primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma owing to the extent of extracutaneous dissemination, including testicular involvement and disease progression despite chemotherapeutic intervention. Although all cases of LyP showed sharp cytoplasmic membrane staining with perinuclear Golgi accentuation with CD30, the recategorized case of aggressive epidermotropic CD8 cytotoxic T-cell lymphoma manifested only a weak cytoplasmic staining pattern. CD8 LyP defines a distinctive entity with characteristic light microscopic and phenotypic findings and has a predilection for young males. CD30 expression can occur in other forms of CD8 lymphoproliferative disease unrelated to primary cutaneous anaplastic large cell lymphoma or LyP.

Adolescent↗

PubMed2005

Clonal light chain restricted primary intrapulmonary nodular amyloidosis.

Primary intrapulmonary nodular amyloidosis is a rare form of immunoglobulin associated amyloidosis, also falling under the alternative appellation of amyloidoma. Although amyloidomas in other organ sites may be reflective of a localized or more generalized plasma cell dyscrasia, in the context of its presentation in the lung the presumptive basis has long been held to be one of chronic inflammation. We encountered 2 patients with nodular amyloidosis in whom the pathologic examination disclosed the basis to be one of a light chain restricted clonal lymphocytic plasma cell infiltrate, although without morphologic features of coexisting pulmonary lymphoma. These 2 patients serve to underscore the potential categorization of some cases of pulmonary nodular amyloidosis as a form of low grade B cell lymphoproliferative disease.

Aged↗

PubMed2005

Epstein-Barr virus- and human herpesvirus 8-associated primary cutaneous plasmablastic lymphoma in the setting of renal transplantation.

BACKGROUND: Plasmablastic lymphoma (PBL) is a recently recognized entity most often reported in the oral cavity, mainly in the setting of underlying human immunodeficiency viral infection whereby a role for Epstein-Barr virus (EBV) and more recently human herpesvirus 8 (HHV8) has been described. Although EBV has been implicated in a variety of lymphoproliferative lesions, until recently HHV8 has only been associated with primary effusion lymphoma, multicentric Castleman's disease, and Kaposi's sarcoma. We describe a case of PBL occurring in the setting of renal transplantation. METHODS: We encountered a case of PBL occurring in the setting of renal transplantation. We characterized the tumor by routine immunohistochemistry and evaluated for the presence of immunoglobulin light chain restriction and EBV RNA by in situ hybridization. We assessed for the presence of HHV8 RNA by reverse transcriptase in situ hybridization. RESULTS: The tumor showed a histomorphology compatible with a PBL. In addition, there was strong RNA expression in the neoplastic cells for EBER-1, EBER-2, and HHV8. CONCLUSION: This case suggests a possible role of both viruses in the pathogenesis of PBL in sites other than the oral cavity and expands the spectrum of post-transplantation lymphoproliferative disease to include PBL.

Adult↗

PubMed2005

The application of a monoclonal antibody to CD62L on paraffin-embedded tissue samples in the assessment of the cutaneous T-cell infiltrates.

BACKGROUND: A reduction in the expression of the pan T-cell markers CD7 and CD62L supports an endogenous T-cell dyscrasia. Previously, clone availability for CD62L restricted its application to frozen tissue sections. MATERIALS AND METHODS: A nonavidin/biotin technique to examine CD3, CD62L, and CD7 in paraffin formalin-fixed tissue in non-neoplastic and neoplastic T-cell infiltrates. RESULTS: In the reactive group, CD62L manifested a 15 and 22% reduction in epidermal and dermal staining, respectively; there was a 42 and 31% reduction in epidermal and dermal CD7 staining. In lymphomatoid hypersensitivity, CD62L showed a 24 and 9% reduction in epidermal and dermal staining, respectively; CD7 staining demonstrated reduced staining by 70 and 66% in the epidermis and dermis. In the non-lymphomatous endogenous T-cell dyscrasia and lymphoma categories, an 80% diminution in CD62L and CD7 expression was seen. CONCLUSIONS: CD62L can be successfully applied in formalin-fixed tissue and exhibits enhanced specificity compared to CD7 in the evaluation of cutaneous T-cell infiltrates. Both CD62L and CD7 in paraffin-embedded, formalin-fixed tissue are useful diagnostic adjuncts, especially in regard to the discrimination of lymphomatoid hypersensitivity reactions from true endogenous T-cell dyscrasia.

Antibodies, Monoclonal↗

PubMed2005

Light-chain-restricted plasmacellular infiltrates in necrobiosis lipoidica -- a clue to an underlying monoclonal gammopathy.

BACKGROUND: Necrobiosis lipoidica (NL) is a member of the palisading granulomatous dermatitides that is associated, in most cases, with diabetes mellitus. However, there are an increasing number of cases of NL associated with other forms of systemic disease. We describe a novel case of NL associated with a light-chain-restricted plasmacellular infiltrate; subsequent investigations established an underlying monoclonal gammopathy. METHODS: Skin biopsy material was obtained and was processed in the usual fashion for hematoxylin and eosin (H and E) examination. Immunohistochemical staining was performed by utilizing kappa and lambda monoclonal antibodies (Dako Corporation, Carpentiera, CA, USA). Kappa and lambda in situ hybridization was also performed (Ventana Medical Systems, Tucson, AZ, USA). RESULTS: A 55-year-old woman with a 5-year history of bilateral thigh subcutaneous nodules underwent a skin biopsy, showing typical changes of NL; there was a concomitant prominent perivascular plasmacellular infiltrate. Kappa light chain restriction was observed amid the plasmacellular infiltrate. Bone marrow biopsy and immunophenotyping studies revealed a clonal plasmacytosis with kappa light chain restriction. CONCLUSIONS: Granulomatous inflammation, including NL, may be a cutaneous paraneoplastic expression of low-grade B-cell lymphoproliferative disease in the context of an underlying plasma cell dyscrasia.

Female↗

PubMed2005

Alpha-1 anti-trypsin deficiency and Henoch-Schönlein purpura associated with anti-neutrophil cytoplasmic and anti-endothelial cell antibodies of immunoglobulin-A isotype.

Alpha-1 anti-trypsin (A1AT) deficiency is an inherited enzyme deficiency that manifests with fatal lung and liver complications. In addition to pulmonary and hepatic involvement, the disease has also been linked to an increased incidence of vasculitic syndromes and autoimmune diseases, including Wegener's granulomatosis, microscopic polyarteritis nodosa and Henoch-Schonlein purpura (HSP). HSP, a systemic, small-vessel vasculitis syndrome, is characterized by a non-thrombocytopaenic purpuric rash, arthralgia, abdominal pain and nephritis. Both A1AT deficiency and HSP have been associated with anti-neutrophil cytoplasmic antibodies (ANCA) and anti-endothelial cell antibodies (AECA). We report a case of a 40-year-old man with severe A1AT deficiency, who developed HSP associated with AECA, ANCA and anti-phospholipid antibodies of the immunoglobulin-A isotype.

Adult↗

PubMed2005

The absence of CD20 messenger RNA in recurrent cutaneous B-cell lymphoma following rituximab therapy.

BACKGROUND: Rituximab has been used to treat relapsed low-grade or advanced non-Hodgkin's lymphoma since 1997, targeting the CD20 antigen expressed by B cells. Single-agent rituximab therapy is safe and well tolerated. Recurrences showing a loss of CD20 expression following rituximab therapy have been reported. METHODS: Four patients with CD20-positive cutaneous B-cell lymphoma received rituximab therapy with subsequent recurrences. The biopsies were assessed for cytoplasmic CD20 expression; CD20 messenger RNA was also assessed where tissue was available. RESULTS: Cutaneous relapses occurring within 1.5-3 months following the last dose of rituximab were CD20 negative. In three cases, subsequent relapses showed renewed expression of CD20. Those biopsies demonstrating a loss of surface and cytoplasmic CD20 by immunohistochemistry also showed no evidence of messenger RNA for CD20 using an in situ polymerase chain reaction-based methodology. CONCLUSIONS: Rituximab may be associated with the emergence of CD20-negative B-cell clones, potentially rendering a tumor insensitive to this drug. Conversely, following cessation of the drug, a re-expression of CD20 within the neoplastic cells may occur allowing therapeutic intervention with this monoclonal antibody. The loss of CD20 expression appears to be a direct effect of the drug on CD20 messenger RNA synthesis.

Adult↗

PubMed2005

De novo intraepidermal epithelioid melanocytic dysplasia as a marker of the atypical mole phenotype -- a clinical and pathological study of 75 patients.

BACKGROUND: We encountered a distinctive pattern of dysplastic intraepidermal melanocytic proliferation, which defies classification as a dysplastic melanocytic nevus, but in which the morphologic features fall short of a diagnosis of melanoma in situ. We designate such lesions as de novo intraepidermal epithelioid melanocytic dysplasia. METHODS: From 75 patients, 82 skin biopsies were encountered that showed this distinctive morphology. Hematoxylin- and eosin-stained histologic sections were studied and the features were correlated with personal and family histories of dysplastic nevi and melanoma. RESULTS: The diagnosis of de novo melanocytic dysplasia was made in 27 male patients and 48 female patients (mean age: 44 years). The histologic hallmark was a pagetoid (single-cell) array of moderately to severely atypical epithelioid melanocytes within the epidermis. Seventy-three lesions were located on sun-exposed skin and nine on sun-protected skin. In 41 patients, there was an atypical mole phenotype, whereas 20 patients had a prior or subsequent diagnosis of melanoma with five of 16 patients questioned revealing a family history of melanoma. CONCLUSIONS: De novo intraepidermal epithelioid melanocytic dysplasia is a distinct entity associated with an atypical mole phenotype and a personal and/or family history of melanoma.

Adolescent↗

PubMed2005

Chondrodermatitis nodularis helicis as a marker of internal disease [corrected] associated with microvascular injury.

Chondrodermatitis nodularis helicis (CNH) is held to be an idiopathic degenerative process involving the upper dermis of the auricular rim. Chondrodermatitis typically occurs in elderly men where associations with underlying trauma and sun exposure have been postulated as potential inciting triggers. Its association as a marker of systemic disease is not well established. We describe 24 patients with CNH, in whom there were also significant underlying diseases largely associated with vascular injury including those of immune-based etiology and/or conditions which have been previously linked with granuloma annulare, another necrobiotic process of collagen. These patients with concomitant systemic disease were characteristically younger compared to the classic demographics described for CNH. In some cases, chondrodermatitis may represent an ischemic necrobiotic disorder of collagen, potentially defining an important sign of underlying systemic disease in younger patients.

Adolescent↗

PubMed2005

Epstein--Barr virus-associated B-cell lymphoma in the setting of iatrogenic immune dysregulation presenting initially in the skin.

BACKGROUND: Epstein-Barr virus (EBV) has been implicated in B-cell lymphoma associated with iatrogenic immune dysregulation, primarily in the context of extracutaneous lymphoma. METHODS: We describe six patients, five transplant recipients receiving cyclosporine and one patient with rheumatoid arthritis receiving methotrexate, who developed cutaneous presentations of EBV-associated B-cell lymphoma. Human herpesvirus 8 (HHV8) and EBV thymidine kinase (vTK) expression were also explored. RESULTS: The cases comprised plasmablastic lymphoma (one case), plasmacytic marginal zone lymphoma (two cases), and diffuse large B-cell lymphoma (three cases). There was a monoclonal gammopathy in one and concurrent extracutaneous disease in two of the six patients. EBV-associated latent small nuclear RNA was detected in all cases with coexpression of HHV8 in one of the five cases and of vTK in three of the six cases. Three patients responded to a reduction in the immunosuppressive regimen and antiviral therapy. Recurrent disease developed in two, with one patient succumbing to multiorgan dissemination. CONCLUSIONS: EBV-associated cutaneous B-cell lymphoma is characterized by a long interval between the initiation of immunosuppression and the development of lymphoma. Although previous reports have reported an indolent clinical course, an aggressive clinical course may occur. HHV8 and lytic phase EBV antigens are detected in some cases, possibly suggesting a pathogenetic role.

Adult↗

PubMed2005

CD34 expression in primary cutaneous malignant melanoma: apropos of a case and review of the aberrant melanoma phenotype.

BACKGROUND: The histological diagnosis of malignant melanoma can be challenging. Immunohistochemical techniques may define a critical role in certain cases, specifically in establishing a primary diagnosis of melanoma. CD34 is a hemopoietic stem cell antigen expressed in bone marrow and endothelial cells, and may also be expressed in vascular and spindle cell tumors; it is generally negative in malignant melanoma. CASE REPORT: An 83-year-old white female presented with a 3-4 mm area on her right upper back, which had been present for several years. Histologic sections showed a polypoid distortion by sheets and nodules of transformed amelanotic melanocytes lying in intimate apposition to an attenuated epidermis without a concomitant radial growth phase. Tumor cells were extensively S-100 and CD34 positive and showed focal immunoreactivity with melan-A and HMB-45. DISCUSSIONS: We present a case of malignant melanoma of nodular subtype, which strongly expressed CD34. The spectrum of abnormal phenotypes in malignant melanoma is reviewed, and a possible explanation for the presence of CD34 is discussed. This case demonstrates the potential of malignant melanoma to express CD34, defining an infrequently recognized aberrant phenotype. Whether or not expression of this marker is associated with a more aggressive clinical course remains to be determined.

Aged, 80 and over↗

PubMed2005

Endobronchial mimics of primary endobronchial carcinoma: a clinical study of 25 cases.

While endobronchial lesions that present with symptoms of obstruction may be reflective of primary bronchogenic malignancy, there have been a number of reports of bronchial lesions other than primary bronchogenic carcinoma simulating primary endobronchial epithelial malignancy clinically. Twenty-five cases of symptomatic endobronchial disease were encountered with pathological assessment demonstrating an endobronchial process other than carcinoma, representing metastatic disease (breast, colon, renal, head and neck origin), fungal infection, Hodgkin's lymphoma, primary bronchogenic melanoma, lipoma, broncholith and inflammatory pseudopolyp. The present report underscores the potential pathogenetic heterogeneity encountered in lesions presenting with signs and symptoms of endobronchial obstruction, emphasizing the critical role of biopsy for establishing a definitive diagnosis.

Adult↗

PubMed2004

A phase I study of interleukin 12 with trastuzumab in patients with human epidermal growth factor receptor-2-overexpressing malignancies: analysis of sustained interferon gamma production in a subset of patients.

PURPOSE: On the basis of preclinical studies, we hypothesized that interleukin (IL)12 would potentiate the antitumor actions of an antihuman epidermal growth factor receptor-2 (HER2) monoclonal antibody (trastuzumab). We conducted a Phase I trial to determine the safety and optimal biological dose of IL-12 when given in combination with trastuzumab. PATIENTS AND METHODS: Patients with metastatic HER2-positive malignancies received trastuzumab on day 1 of each weekly cycle. Beginning in week 3, patients also received intravenous injections of IL-12 on days 2 and 5. The IL-12 component was dose-escalated within cohorts of 3 patients (30, 100, 300, or 500 ng/kg). Correlative assays were conducted using serum samples and peripheral blood cells obtained during the course of therapy. RESULTS: Fifteen patients were treated, including 12 with HER2 2+ or 3+ breast cancer. The regimen was well tolerated with IL-12-induced grade 1 nausea and grade 2 fatigue predominating. Evaluation of dose-limiting toxicity and biological end points suggested that the 300 ng/kg dose was both the maximally tolerated dose and the optimal biological dose of IL-12 for use in combination with trastuzumab. Two patients with HER2 3+ breast cancer within the 500 ng/kg dose level experienced grade 1 asymptomatic decreases in left ventricular ejection fraction of 12% and 19% after 3 and 10 months of therapy, respectively. There was one complete response in a patient with HER2 3+ breast cancer metastatic to the axillary, mediastinal, and supraclavicular nodes, and 2 patients with stabilization of bone disease lasting 10 months and >12 months, respectively. Correlative assays showed sustained production of interferon (IFN)gamma by natural killer cells only in those patients experiencing a clinical response or stabilization of disease. Elevated serum levels of macrophage inflammatory protein-1alpha, tumor necrosis factor-alpha, and the antiangiogenic factors IFN-gamma inducible protein-10 and monokine induced by gamma were also observed in these patients. Patient genotyping suggested that a specific IFN-gamma gene polymorphism might have been associated with increased IFN-gamma production. The ability of patient peripheral blood cells to conduct antibody-dependent cellular cytotoxicity against tumor targets in vitro did not correlate with clinical response or dose of IL-12. CONCLUSIONS: The addition of IL-12 to trastuzumab therapy did not appear to enhance the efficacy of this antibody treatment. Sustained production of IFN-gamma and other cytokines were observed in three patients: One who exhibited a complete response and two others who had stabilization of disease lasting over 6 months. Given the small sample size and heterogeneity of the patient population, the effects of IL-12 on the innate immune response to trastuzumab therapy should be further explored in the context of a larger clinical trial.

Adult↗

PubMed2004

Endobronchial histoplasmosis: a masquerade of primary endobronchial neoplasia--a clinical study of four cases.

BACKGROUND: Histoplasma capsulatum is a dimorphic fungus with both hyphal and microconidial elements and is endemic in certain areas of the central United States. Most clinically recognized syndromes are self-limited, presenting in more than 80% of cases as an influenza-like acute pulmonary illness. We encountered four patients with an endobronchial presentation of histoplasmosis masquerading as a bronchogenic malignancy. METHODS: The patient files from one of the authors (PR) uncovered four patients diagnosed with, and treated for, endobronchial histoplasmosis; all cases were referred for a presumptive diagnosis of endobronchial neoplasia. RESULTS: The case study group comprised three women, ages 52, 68, and 81 years, respectively, and one man age 29 years, all presenting with recurrent hemoptysis. An obstructing adherent lesion was apparent on bronchoscopy in three, involving the right upper lobe bronchus in two, and right mainstem bronchus in one. In one patient, blood was observed in the bronchus intermedius; there was no gross lesion. Recurrent hemoptysis necessitated a right upper sleeve lobectomy in one, a right upper lobe lobectomy and right lower wedge resection in one, a right middle lobectomy in one, and wedge resection of the right upper lobe in one. CONCLUSIONS: Endobronchial histoplasmosis may mimic primary bronchogenic carcinoma, presenting as a fixed obstructing endobronchial lesion associated with hemoptysis; the latter potentially necessitating surgical intervention. Endobronchial histoplasmosis should be considered in the differential diagnosis of obstructing endobronchial lesions associated with hemoptysis, especially when prior and(or) concurrent biopsies fail to disclose malignancy.

Adult↗

PubMed2004

Atypical thymoma: a report of seven patients.

BACKGROUND: Most thymic neoplasms fall under the designation of thymoma, consisting of well-differentiated epithelial cells, resembling normal thymus. At the opposite spectrum are thymic carcinomas; the cell of origin while similar is malignant. Recently a third category of thymic neoplasms, atypical thymomas, has been recognized representing thymic neoplasms manifesting atypia although without overt cytomorphologic criteria of malignancy. METHODS: Seven patients with a diagnosis of atypical thymoma were encountered over a 6-year period from the patient files of the cardiothoracic division of The Ohio State Medical Center. RESULTS: In all patients there was gross or light microscopic invasive disease with involvement of the capsule, phrenic nerve, diaphragm, chest wall, and lung. Surgical extirpation/de-bulking along with radiation therapy in six and chemotherapy in one led to complete disease regression. Intrathoracic recurrences developed in 4 involving lung, pleura, chest wall and diaphragm. All patients are well. CONCLUSIONS: Atypical thymomas are locally aggressive tumors with a high incidence of intrathoracic recurrence; extrathoracic spread is not seen. Our study corroborates other reports that death attributable to atypical thymoma is uncommon.

Adult↗