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Earl J Glusac

Publications and source records attributed to Earl J Glusac.

At least 19 recordsLinked to original sources
PubMed2006

Transimmunization for cutaneous T cell lymphoma: a Phase I study.

Extracorporeal photochemotherapy (ECP) is a widely used immunotherapy for cutaneous T cell lymphoma (CTCL). It involves four sequential steps: conversion of blood monocytes into dendritic antigen presenting cells (DC) by repetitive adherence and disadherence to plastic surface; reinfusion of the new DC; presumed in vivo loading of the new DC with apoptotic malignant leukocytes; and expansion of the anti-tumor CD8 T cell pool. To assess the safety of a methodology designed to increase ex vivo contact between the apoptotic malignant cells and new DC prior to reinfusion, a single-center, open-label Phase I clinical study of a revised procedure--referred to as "Transimmunization"--was conducted in CTCL patients. Twenty-seven subjects were treated monthly for 3 to 5 months, alone or in combination with electron beam therapy. For those receiving Transimmunization alone, there was an overall diminution in infiltrative lesions in eleven (55%) of twenty patients. In the twelve leukemic CTCL patients, there was a significant mean reduction of 50.1% in the circulating malignant cells, as determined with family-specific anti-T cell receptor Vbeta monoclonal antibodies (P <or= 0.021). Because this therapy permits the synchronous induction and tumor loading of DC, with minimal toxicity, Transimmunization may merit further investigation in CTCL and other malignancies.

Adult↗
PubMed2006

p63 is a useful marker for cutaneous spindle cell squamous cell carcinoma.

BACKGROUND: Cutaneous spindle cell squamous cell carcinoma (SCSCC) is a rare variant of SCC. This lesion is sometimes difficult to diagnose based purely on morphologic features. p63 is a member of the p53 gene family that can be identified in epithelial malignancies. METHODS: Thirteen cases of spindle SCC were stained with p63, CK34betaE12, MNF116, vimentin, and S100. Control cases included desmoplastic melanoma (eight cases), atypical fibroxanthoma (AFX) (10 cases), dermatofibrosarcoma protuberans (eight cases), and cutaneous leiomyosarcoma (LMS) (four cases). RESULTS: p63 was expressed diffusely in the nuclei of 100% (13/13) of SCSCCs. Of controls, p63 showed focal labeling of two LMS and two AFX. MNF116 and CK34betaE12 were positive in 13/13 SCSCCs. Of controls, one LMS was focally positive for MNF116. All SCSCCs and all control cases were positive for vimentin. CONCLUSIONS: In the given differential diagnosis, p63 appears relatively specific to SCSCC and adds a useful nuclear marker to the available repertoire. The findings also suggest that cytokeratins MNF116 and CK34betaE12 may be more useful than standard cytokeratins in labeling SCSCC.

Adult↗
PubMed2005

The characteristic histopathologic features of nevi on and around the ear.

BACKGROUND: Nevi on certain areas of the body such as the acral, genital, and flexural regions may exhibit uncommon but characteristic histopathologic features. The purpose of this study was to characterize the distinctive features of nevi with a junctional component located on and around the ear. MATERIALS AND METHODS: A total of 101 compound and junctional nevi of the ear received at the Yale Dermatopathology Laboratory during a 10-year period were examined in this study. The most characteristic feature of the majority of these nevi was irregularity of nesting pattern, with nests, which varied in size and shape and which were sometimes located between rete ridges. RESULTS: Forty-two (42%) of nevi on and around the ear showed poor circumscription, lateral extension of the junctional component beyond the dermal component, and elongation of rete ridges with bridging between them. A subset of these nevi (26 cases) showed uniformly large melanocytes with large vesicular nuclei without prominent nucleoli, and abundant pale, finely granular cytoplasm. These lesions did not show a tendency to recur. CONCLUSIONS: This study supports the existence of a subset of nevi on or near the ear that, like certain nevi located on other special sites, exhibit unusual but characteristic features, which may be misinterpreted as atypical or malignant.

Adolescent↗
PubMed2005

Fatal subcutaneous panniculitis-like T-cell lymphoma with interface change and dermal mucin, a dead ringer for lupus erythematosus.

We report a 48-year-old man who presented with ulcerated plaques and nodules of the lower extremities. Skin biopsies revealed a dense lymphocytic infiltrate involving the dermis and the subcutis in a lobular and septal pattern. No overt cytological atypia was present. Notably, several features resembling lupus erythematosus were present, including vacuolar interface change and abundant dermal mucin deposition. The patient developed pulmonary nodules, and a lung biopsy showed a perivascular and interstitial lymphoid infiltrate without overt atypia. The cutaneous and pulmonary lymphoid infiltrates showed similar immunohistochemical profiles: CD3(+) CD4(-) CD8(+/-) CD56(+). Monoclonal rearrangements of the T-cell receptor gamma gene with similar migration patterns were identified from both locations. The patient developed fatal hemophagocytic syndrome, involving liver, spleen, lymph nodes, and bone marrow. This case is one amongst the rare reports of subcutaneous panniculitis-like T-cell lymphoma with systemic involvement.

Dermis↗
PubMed2005

Cellular digital fibromas: distinctive CD34-positive lesions that may mimic dermatofibrosarcoma protuberans.

BACKGROUND: Digital fibromas are common benign acral tumors typically reported as angiofibromas (AFs) or acquired digital fibrokeratomas (ADFs). Cellular variants are not well recognized. METHODS: We collected 14 acral fibrocytic lesions showing a spindle cell morphology from our files, and evaluated CD34, Factor XIIIa, epithelial membrane antigen (EMA), and S100 protein staining of these lesions. We compared the histologic and immunohistochemical features of these cellular fibromas with five digital AFs, five ADFs, and five digital dermatofibromas. RESULTS: The 14 cellular digital fibromas showed intersecting fascicles of thin delicate bland spindle cells in the superficial reticular dermis with a fibrotic-to-slight myxoid stroma. The spindle cells in all cases stained strongly for CD34, and only scattered stromal cells stained for Factor XIIIa. Five tested cases were negative for EMA and S100 protein. The digital AFs, fibrokeratomas, and dermatofibromas stained predominately for Factor XIIIa, with no or minimal staining for CD34. CONCLUSIONS: These findings suggest that a subset of digital fibromas is characterized by a dense cellular proliferation of CD34-positive spindle cells. Awareness of this variant of digital fibroma and its staining pattern is critical in preventing misdiagnosis as dermatofibrosarcoma protuberans, particularly in superficial biopsies.

Adult↗
PubMed2005

CD56 staining in Merkel cell carcinoma and natural killer-cell lymphoma: magic bullet, diagnostic pitfall, or both?

BACKGROUND: Antibodies to CD56 label natural killer (NK) cell lymphomas and neuroendocrine tumors such as Merkel cell carcinoma (MCC). In MCC altered by crush artifact or obscured by lymphocytes, the histologic features coupled with CD56 positivity can lead to an erroneous impression of NK-cell lymphoma. METHODS: Eighteen cases of MCC were stained for CD56, CK20, MNF116, and pankeratin. The results were compared to histologic features and CD56 staining pattern of three NK-cell lymphomas. RESULTS: Three of 18 cases of MCC histologically resembled lymphoma, and CD56 positivity with CD3 and CD20 negativity initially raised the possibility of NK-cell lymphoma. Two additional cases were obscured by dense inflammation, again suggesting the diagnosis of lymphoma. Seventeen of 18 MCC labeled for CD56 and an equal number stained for CK20. All MCC tested were positive for CAM5.2 (14/14) and MNF116 (17/17). Antibodies to pankeratin labeled only one of 18 MCC. Staining for CD56 was stronger in MCC than NK-cell lymphomas. CONCLUSIONS: CD56 is a sensitive marker for MCC as well as for NK-cell lymphoma, but is not specific. Importantly, CD56 positivity in crushed or inflamed biopsies of MCC may lead to an erroneous impression of NK lymphoma. Awareness of this potential pitfall will prevent misdiagnosis. McNiff JM, Cowper SE, Lazova R, Subtil A, Glusac EJ. CD56 staining in Merkel cell carcinoma and natural killer-cell lymphoma: Magic bullet, diagnostic pitfall, or both?

Aged↗
PubMed2004

Primary cutaneous B-cell lymphoma treated with radiotherapy: a comparison of the European Organization for Research and Treatment of Cancer and the WHO classification systems.

PURPOSE: To determine the relationship between the WHO and European Organization for Research and Treatment of Cancer (EORTC) pathologic classifications for primary cutaneous B-cell lymphoma (CBCL) and the implication of this relationship on initial treatment. PATIENTS AND METHODS: Patients with primary CBCL treated with radiotherapy were identified retrospectively. Initial biopsy specimens were reviewed by two dermatopathologists and classified according to the EORTC and WHO systems. Primary outcomes were recurrence-free and overall survival. RESULTS: Thirty-four patients were identified; initial biopsy specimens were adequate for classification in 32 patients. Four different composite histopathologic subtypes of lymphoma were identified: 53% (17 of 32) follicle center cell by EORTC and diffuse large B-cell by WHO (FCC/DLB), 25% (eight of 32) follicle center cell by EORTC and follicular by WHO (FCC/Fol), 13% (four of 32) marginal zone by EORTC and WHO (MZ/MZ), and 9% (three of 32) large B-cell of the leg by EORTC and diffuse large B-cell by WHO (Leg/DLB). Five-year relapse-free survival ranged from 62% to 73% for FCC/DLB, FCC/Fol, and MZ/MZ but was 33% for Leg/DLB (P =.6). Five-year overall survival was 100% for FCC/DLB, FCC/Fol, and MZ/MZ but was 67% for Leg/DLB (P =.07). At 5 years, 21% of all patients had developed extracutaneous disease. CONCLUSION: Two-thirds of primary cutaneous FCC lymphomas by EORTC criteria satisfy WHO criteria for DLB lymphoma. Unlike DLB lymphoma presenting in nodal or noncutaneous sites, these lesions are associated with an indolent course and may be treated with local radiotherapy alone.

Aged↗
PubMed2004

Characterizing the protective component of the alphabeta T cell response to transplantable squamous cell carcinoma.

There is increasing promise that cellular immune response may be manipulated to combat cancer; however, it is also clear that the immune response to cutaneous malignancy comprises different T cell activities that variably inhibit or promote tumor development. Thus, a better understanding of each of these activities is crucial to more effective clinical manipulation. To better characterize the protective anti-tumor effects of alphabeta T cells, we examined the growth of the transplantable squamous cell carcinoma (SCC) line, PDV, which is markedly inhibited in immunocompetent versusalphabeta T cell-deficient mice. We show that the protective response is composed of CD8(+) and interferon-gamma (IFNgamma)-producing CD4(+) cells, and that the most overt effects of these components on tumor growth in situ are to provoke overt focal necroses and to decrease the stromal bed. Tumors growing in the presence of any of these components also show reduced expression of Rae-1, a ligand for the activating NK receptor, NKG2D. Collectively, these data illustrate which components of the alphabeta T cell response against SCC have protective potential, and indicate which aspects of tumor physiology may be most susceptible to their activities.

Animals↗
PubMed2004

Early histopathologic changes in purple glove syndrome.

An 86-year-old African-American man presented with tonic-clonic seizures. Intravenous phenytoin was urgently administered into the dorsum of the right hand. The patient developed a raised purple area of discoloration around the intravenous insertion site within 2 h and edema and vesiculobullous lesions of the distal forearm, hands, and fingers within 8 h. Microscopic sections from a biopsy at 12 h revealed epidermal necrosis, superficial ulceration, and a mild superficial and deep perivascular lymphoid infiltrate, associated with numerous thrombi of small vessels throughout the dermis. The findings were judged to be consistent with soft-tissue injury associated with intravenous administration of phenytoin, also termed purple glove syndrome. Purple glove syndrome, named for its distinctive purple discoloration and swelling of the hands in the distribution of a glove, is an uncommon complication of intravenous phenytoin administration through small dorsal veins of the hands. It is comprised by pain, discoloration, and edema in the vicinity of intravenous infusion of phenytoin through dorsal veins of the hand. The histopathologic features of fully developed lesions have been reported; however, early-stage findings have not been previously described, and the histogenesis of this lesion is controversial. The presence of thrombi in this early-stage lesion suggests that thrombosis plays a role in the initial pathogenesis of this condition.

Aged↗
PubMed2004

The clinical appearance of clonal nevi (inverted type A nevi).

BACKGROUND: The term "clonal nevus" is used to describe a variant of melanocytic nevus that histologically exhibits a localized proliferation of pigmented epithelioid dermal melanocytes within an otherwise ordinary nevus (Ball NJ, Golitz LE. Melanocytic nevi with focal atypical epithelioid cell components: a review of seventy-three cases. J Am Acad Dermatol 1994; 30: 724-729). Reports to date have focused on the histologic appearance of these lesions. AIM: To characterize the clinical appearance of clonal nevi. METHODS: Clinical and histologic examinations were performed of a single clonal nevus from each of five patients (two men and three women; age range, 37-80 years). RESULTS: All nevi were round to oval in shape with smooth, well-defined borders. They were uniformly tan to light brown in color, except for a single blue-gray to blue-black focus of hyperpigmentation. The diameters of the nevi ranged from 2.5 to 10 mm. In individual nevi, the hyperpigmented focus was either centrally or eccentrically located and measured 1-2 mm in diameter. Histologically, these lesions showed banal melanocytes associated with a localized proliferation of melanocytes with abundant pigmented cytoplasm in the dermis, admixed with melanophages. CONCLUSIONS: The appearance of clonal nevi--tan with a focus of blue-gray to blue-black pigmentation--allows one to recognize the lesion clinically.

Adult↗
PubMed2003

Sezary syndrome: cutaneous immunoperoxidase double-labeling technique demonstrates CD4/CD8 ratio non-specificity.

BACKGROUND: Sezary syndrome (SS) is an erythrodermic cutaneous T-cell lymphoma with a leukemic component. Biopsies from these patients may suggest erythrodermic mycosis fungoides or SS but most often are not diagnostic. Additional methods are therefore usually needed to diagnose SS. These include a peripheral blood morphological assessment, flow cytometry, and gene rearrangement studies. The Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer has proposed criteria for the diagnosis of SS based on peripheral blood analysis. These include an increased T-cell count with a CD4/CD8 ratio of > or =10, in conjunction with evidence of a T-cell clone in the blood (Willemze et al., Blood 1997; 90: 354-371). METHODS: We have conducted a study designed to obtain CD4/CD8 ratios by immunoperoxidase staining of skin biopsies, as opposed to flow cytometry. Fourteen biopsies from eight patients with SS and 14 control biopsies were evaluated for CD4/CD8 ratio via double immunostaining. RESULTS: A CD4/CD8 ratio of >10:1 was seen in 85% of SS biopsies and 43% of controls with horseradish peroxidase used as the CD4 antibody. With alkaline phosphotase used as the CD4 antibody, 54% of SS biopsies and 21% of control biopsies exhibited a >10:1 ratio. We demonstrate that double-labeling immunoperoxidase staining with antibodies to CD4 and CD8 on skin biopsies is not specific for SS. By comparing the CD4/CD8 ratios from skin biopsies in Sezary cases with those from biopsies in inflammatory dermatoses cases, we conclude that flow cytometry remains the most specific method for determining the CD4/CD8 ratios in patients with cutaneous eruptions. Although immunohistochemistry would be useful for laboratories with limited access to flow cytometry, we dismiss such a use, as CD4/CD8 ratios > or =10 were also found in 21-43% of non-Sezary cases examined. CONCLUSIONS: We conclude that a CD4/CD8 ratio >10:1 on skin biopsy is not sufficiently specific to support a diagnosis of SS.

Alkaline Phosphatase↗
PubMed2003

Brainstem involvement by mycosis fungoides in a patient with large-cell transformation: a case report and review of literature.

BACKGROUND: Central nervous system (CNS) involvement by mycosis fungoides (MF) is rare. As compared to meningeal involvement, intraparenchymal spread is especially rare. It is usually seen in advanced disease in conjunction with lymph node or visceral involvement. However, CNS involvement in the absence of progressive skin lesions or other extracutaneous involvement has been reported rarely in patients with transformed MF. METHOD: Case report and review of literature. RESULTS: A 71-year-old female with long-standing MF developed lymphomatous CNS involvement 10 years after the diagnosis of tumor stage MF. At this time, the patient presented with a transient episode of garbled speech followed by generalized weakness. Computerized tomography scan (CT scan) and magnetic resonance imaging scan (MRI scan) of the head revealed a subcortical lesion in the left temporo-frontal lobe. Cerebrospinal fluid (CSF) examination showed atypical T cells, and brain biopsy confirmed parenchymal involvement by T-cell lymphoma. Meanwhile, a biopsy of a skin lesion showed large-cell transformation. No lymph node or other systemic involvement was noted at this time, and the patient was treated with chemotherapy. Twelve months later, the patient developed recurrent CNS lymphoma with multiple organ involvement and expired soon thereafter. CONCLUSIONS: This case illustrates the importance of awareness of the possibility of CNS involvement by MF, especially in transformed MF. CNS involvement may be the only site of extracutaneous involvement in patients with transformed MF, and mental status changes warrant CNS surveillance for this disease.

Aged↗
PubMed2003

Epithelioid cell histiocytoma--histogenetic and kinetics analysis of dermal microvascular unit dendritic cell subpopulations.

BACKGROUND: Epithelioid cell histiocytoma (ECH), also known as epithelioid fibrous histiocytoma, is a peculiar dermal tumor, which can mimic melanocytic, vascular, epithelial, or other histiocytic lesions. Thought to arise from dermal dendrocytes, most ECH contain approximately 50% FXIIIa+ histiocytic dendrocytes, but not all lesional cells express FXIIIa. A putative fibroblastic component has not been characterized. METHODS: We analyzed the differentiation and cell kinetics of dermal microvascular unit cells in 12 previously reported ECH using antibodies to FXIIIa, CD68 (KP1), CD34, CD117, CD31, smooth muscle actin, collagen type 1 aminopropeptide, and MIB-1, using single and double immunostains. RESULTS: In ECH, many variably sized CD34/CD31+ tumor vessels with actin+ myopericytes were surrounded by epithelioid-to-dendritic cells of three types. About 5-80% were dendritic histiocytes that expressed FXIIIa but not CD31 or KP1. Fibroblasts, in some cases showing mild nuclear pleomorphism, were usually collagen type 1+, but CD34 and actin- in 11/12 cases. One 'early' ECH had 40% CD34+ epithelioid cells, admixed with 50% FXIIIa+ histiocytes. Most ECH had about 2-20% KP1+, CD117+ mast cells. Mast cell numbers increased with FXIIIa+ histiocyte numbers and the intensity of FXIIIa expression. MIB-1/FXIIIa double-labeling showed only rare cycling histiocytes, with numerous cycling fibroblasts and endothelial cells. CONCLUSIONS: Our findings support the impression that ECH is a vascular fibrous histiocytoma. The constituent cells appear to arise from the activation of resident microvascular CD34+ dermal fibroblasts and the accumulation of FXIIIa+ dendritic stromal assembly histiocytes. The CD34+ cells appear to differentiate toward collagenous fibrocytes in association with histiocytes and mast cells in forming collagenous stroma and vessels. ECH is a tumor composed of all requisite cell types consistent with the origin from the dermal microvascular unit.

Antigens, CD↗
PubMed2003

Histologic features of melanocytic nevi seen in association with mycosis fungoides.

BACKGROUND: Many different tumors have been reported to occur simultaneously as collision lesions. To date, no such events have been reported between mycosis fungoides (MFs) and melanocytic neoplasms. METHODS: Two cases are presented in which patches of MF were superimposed on melanocytic nevi. In addition, 967 biopsies of MF from 411 patients were identified in an 8-year retrospective database search. Patient pathology history summaries were reviewed to identify inflamed nevi, atypical nevi, and melanoma submitted for histologic evaluation from this population. RESULTS: The occurrence of MF in a congenital nevus was associated with a halo phenomenon restricted to the affected region of the nevus in one patient. In the other patient, nests of two morphologies (lymphocytic and melanocytic) in the same biopsy presented a potentially confusing histologic picture. No other cases of MF superimposed on a nevus were identified in 967 biopsies from 411 patients with a histological diagnosis of MF seen over the past 8 years. In this population, 57 biopsies of melanocytic lesions were identified from 28 patients, including three atypical nevi and three melanomas. CONCLUSIONS: The presence of MF superimposed on a nevus is rare and may lead to confounding histologic features or the development of a halo nevus phenomenon.

Adult↗