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J R Goldblum

Publications and source records attributed to J R Goldblum.

At least 19 recordsLinked to original sources
PubMed2003

Can extent of high grade dysplasia in Barrett's oesophagus predict the presence of adenocarcinoma at oesophagectomy?

BACKGROUND: Optimal management of Barrett's oesophagus complicated by high grade dysplasia is controversial. Recently, the extent of high grade dysplasia was described as a predictor of subsequent development of cancer in patients undergoing continued surveillance. However, there is no universal agreement on the definition of extent of high grade dysplasia. AIM: To determine if extent of high grade dysplasia in Barrett's oesophagus is a predictor of the presence of adenocarcinoma at the time of oesophagectomy. METHODS: Forty two patients with Barrett's oesophagus and high grade dysplasia who underwent oesophagectomy between 1985 and 1999 were identified from a prospective database. All pathological specimens, including preoperative endoscopic biopsies and post-oesophagectomy sections, were reviewed in a blinded fashion by one expert gastrointestinal pathologist to determine the extent of high grade dysplasia. The extent of high grade dysplasia was defined using two different criteria, one from the Cleveland Clinic and one from the Mayo Clinic. RESULTS: Twenty four of 42 patients (57%) had unsuspected cancer at the time of oesophagectomy. Using the Cleveland Clinic definition, 10 of 21 (48%) patients with focal high grade dysplasia had carcinoma compared with 14 of 21 patients (67%) with diffuse high grade dysplasia (p=0.35). Using the Mayo Clinic definition, adenocarcinoma was found in five of seven (72%) patients with focal high grade dysplasia compared with 19 of 35 (54%) with diffuse high grade dysplasia (p=0.68). CONCLUSIONS: The extent of high grade dysplasia, regardless of how it is defined, does not predict the presence of unsuspected adenocarcinoma at oesophagectomy. There is no evidence as yet that the extent of high grade dysplasia can be used as a basis for decision making in these patients.

Adenocarcinoma↗
PubMed2002

Leiomyosarcoma of the head and neck: a clinicopathological study.

AIMS: The behaviour of leiomyosarcoma is site-related and there are few data on such tumours located in the head and neck. We studied the clinicopathological features of these lesions. METHODS AND RESULTS: Cases diagnosed as leiomyosarcoma of the head and neck were retrieved from the archives of three institutions. Immunohistochemistry was performed and follow-up information was obtained. There were seven men and six women, aged 21-73 years, and lesions involved the neck (n=3), maxilla (n=4), buccal area (n=3), and maxillary sinus, nose, and pharynx (n=1 each). Tumours ranged from 10 to 80 mm. All tumours showed at least focally typical histological features of leiomyosarcoma with perpendicularly arranged fascicles of smooth muscle cells with blunt-ended nuclei, eosinophilic cytoplasm and paranuclear vacuoles. They expressed muscle-specific actin (8/9), smooth muscle actin (7/9), and desmin (10/12). Follow-up information was available on nine patients. All had surgery, with radiation and/or chemotherapy in seven. Three (27%) recurred at 6-24 months; in one case twice. Five (56%) had metastases, including the three with prior recurrences at 1-128 months. Five (including two who received adjuvant therapy) were disease-free at a median of 47 months, one was alive with metastatic disease at 24 months), and three were dead of disease (median 13 months). CONCLUSIONS: Head and neck leiomyosarcomas are rare and aggressive neoplasms which metastasize. Adjuvant therapy has limited effect.

Actins↗
PubMed2002

Observer variation in the diagnosis of superficial oesophageal adenocarcinoma.

BACKGROUND AND AIMS: When to perform oesophagectomy for neoplastic progression in Barrett's oesophagus is controversial. Some resect for high grade dysplasia whereas others defer treatment until intramucosal adenocarcinoma is diagnosed. Interobserver agreement for a diagnosis of high grade dysplasia or intramucosal adenocarcinoma remains unknown and may have therapeutic implications. METHODS: Histological slides from 75 oesophagectomy specimens with high grade dysplasia or T(1) adenocarcinoma were blindly reviewed by two gastrointestinal pathologists and one general surgical pathologist, and classified as high grade dysplasia, intramucosal adenocarcinoma, or submucosal adenocarcinoma. A subsequent re-review of all 75 cases by the same observers following establishment of uniform histological criteria was undertaken. Interobserver agreement was determined by kappa statistics. Coefficients <0.21, 0.21-0.40, 0.41-0.60, 0.61-0.80, and >0.80 were considered poor, fair, moderate, good, and very good agreement, respectively. RESULTS: Interobserver agreement among all pathologists and between gastrointestinal pathologists when comparing high grade dysplasia with intramucosal adenocarcinoma was only fair (k=0.42; 0.56, respectively) and did not substantially improve on subsequent re-evaluation following establishment of uniform histological criteria (K=0.50; 0.61, respectively). CONCLUSIONS: When evaluating resection specimens and after implementation of uniform histological criteria, even experienced gastrointestinal pathologists frequently disagree on a diagnosis of high grade dysplasia versus intramucosal adenocarcinoma. Treatment strategies based on the histological distinction of high grade dysplasia from intramucosal adenocarcinoma using limited biopsy specimens should be re-evaluated.

Adenocarcinoma↗
PubMed2001

The utility of cytokeratin 5/6 in the recognition of cutaneous spindle cell squamous cell carcinoma.

BACKGROUND: Cutaneous spindle cell squamous cell carcinoma (SSCC) is a challenging diagnosis since it may be difficult to distinguish from spindle cell melanoma, leiomyosarcoma and atypical fibroxanthoma. Furthermore, it may be difficult to demonstrate epithelial differentiation by a traditional immunohistochemical panel. We performed an expanded immunohistochemical evaluation of ultrastructurally documented SSCC to assess its utility in diagnosing this entity. METHODS: We identified 16 cases of SSCC that were composed predominantly of spindle-shaped cells and with ultrastructural evidence of epithelial differentiation (i.e. at least rudimentary cell junctions). Immunohistochemical analysis using antibodies to a variety of cytokeratins (AE1/3, K903, CK5/6) and S-100 protein was performed. The extent of immunostaining was graded on a scale of 0 to 4+ (0: no staining; 1+: < or =25%; 2+: 26-50%; 3+: 51-75%; 4+: >75%). RESULTS: Of the 16 cases, 6 expressed AE1/3 (38%), 8 expressed K903 (50%) and 11 (69%) expressed CK5/6. Six cases were positive for all three CK markers and two cases were positive for both K903 and CK5/6 but negative for AE1/3. Three cases (19%) stained for CK5/6 without any staining for AE1/3 or K903. Five cases (31%) were negative for all epithelial markers. The extent of CK5/6 staining was either similar to or greater than K903 staining in 7 of 8 cases that stained with both markers. All 16 cases were negative for S-100 protein. CONCLUSIONS: Including CK5/6 in the initial battery of immunostains performed on a cutaneous spindle cell neoplasm can help demonstrate epithelial differentiation in SSCC, even in the absence of AE1/3 or K903 staining. However, some cases of cutaneous SSCC can only be confirmed ultrastructurally, as up to one-third may not show evidence of epithelial differentiation using an expanded immunohistochemical panel.

Carcinoma, Squamous Cell↗
PubMed2001

Pleomorphic liposarcoma: a clinicopathologic analysis of 19 cases.

Pleomorphic liposarcoma is a variant of liposarcoma defined morphologically by the presence of pleomorphic lipoblasts. Because of its rarity, there are limited studies with long-term follow-up information. Nineteen pleomorphic liposarcomas were studied. Unequivocal pleomorphic lipoblasts were required for inclusion. In each case, the following features were noted: tumor site; tumor size; tumor depth; predominant histologic pattern (epithelioid or malignant fibrous histiocytoma [MFH]-like); extent of necrosis (absent, less than 15%, or at least 15%); mitotic counts; treatment and clinical follow-up. Patients were 11 females and 8 males, aged 33-87 years (mean, 64.5 y; median, 70 y). Tumors involved the extremities (13 patients: intramuscular in 10, subcutaneous in 2, depth unknown in 1), retroperitoneum (4 patients), mediastinum (1 patient), and paratesticular region (1 patient). Size ranged from 4.5--31 cm (mean, 11.9 cm; median, 12.0 cm). Predominant pattern was epithelioid in 7 and MFH-like in 12. Necrosis was present in 15 (79%) and was extensive (36 15%) in 14 patients. Mitotic counts ranged from 0.2--3.4/10 high-power fields (mean, 1.4; median, 1.4) by the average-count method and from 1--6/10 high power fields by the highest count method (mean, 2.9; median, 3.0). All patients were treated surgically; 10 patients received adjuvant chemotherapy and/or radiation therapy. On follow-up of 18 patients (range, 2--129 mo; mean, 35.4 mo; median, 23 mo) nine (50%) were dead of disease (range, 2--48 mo; mean, 20.1 mo; median, 12 mo), one died of other causes 2 months after diagnosis, two were alive with disease, five were disease free, and one was alive at 129 months (tumor status unknown). Five had recurrences (range, 3--28 mo; mean, 14.4 mo; median, 8 mo), and four of five (80%) with recurrences were dead of disease. Metastases developed in eight patients (range, 4--48 mo; mean, 19.5 mo; median, 11.5 mo), most commonly to the lungs. In conclusion, pleomorphic liposarcoma is a rare tumor of adulthood that occurs most commonly in the deep, soft tissues of the extremities. It behaves as a high-grade sarcoma that frequently metastasizes, most commonly to the lungs. Although this tumor has a wide range of histologic appearances, no clinical or pathologic feature is predictive of a more aggressive clinical course.

Adult↗
PubMed2001

Florid vascular proliferation of the colon related to intussusception and mucosal prolapse: potential diagnostic confusion with angiosarcoma.

With the exception of angiodysplasia, vascular abnormalities of the intestines are unusual. We describe a florid benign vascular proliferation of the colon in five adult patients, three of whom presented with idiopathic intussusception. In all cases, the proliferation was sufficiently exuberant to raise the possibility of angiosarcoma as a diagnostic consideration. The group included 2 males and 3 females with a median age of 43 years. Two patients were HIV positive. Four patients presented with a colonic mass; other symptoms at presentation included abdominal pain, diarrhea, bleeding, and bowel obstruction. In all cases, a florid lobular proliferation of small vascular channels lined by plump endothelial cells extended from the submucosa through the entire thickness of the bowel wall. The endothelial cells showed minimal nuclear atypia, and mitotic figures were infrequent. The overlying mucosa showed ulceration with ischemic-type changes, and had features of mucosal prolapse. A possible underlying arteriovenous malformation was identified in two cases. All patients were alive and well at last follow-up (interval, 6 months to 5 years). The presence of intussusception or mucosal prolapse in all of the cases suggests repeated mechanical forces applied to the bowel wall as a possible etiologic factor. The role of HIV infection in the pathogenesis of these lesions remains to be determined.

Adult↗
PubMed2001

The utility of cytokeratin subsets in distinguishing Barrett's-related oesophageal adenocarcinoma from gastric adenocarcinoma.

AIMS: Accurate tumour classification is critical for meaningful epidemiological studies in the assessment of cancer incidence rates and trends. Differentiating primary gastric carcinoma from oesophageal carcinoma can be difficult, especially when tumours are large and involve both the oesophagus and stomach. Furthermore, adenocarcinomas of both organs typically are of intestinal histological type and arise in a background of intestinal metaplasia. Consequently, histological markers that reliably distinguish Barrett's-related oesophageal adenocarcinoma from gastric adenocarcinoma would be useful. Cytokeratins (CK)7 and 20 are cytoplasmic structural proteins with restricted expression that help to determine the origin of many epithelial tumours including those of the gastrointestinal tract. The aim of this study was to determine the utility of co-ordinate CK7 and 20 expression in the distinction of Barrett's-related oesophageal adenocarcinoma from gastric adenocarcinoma arising in a background of intestinal metaplasia. METHODS AND RESULTS: CK7 and 20 immunostaining was performed on randomly selected surgical resection specimens from patients with Barrett's-related oesophageal adenocarcinoma (n = 30) and intestinal type gastric adenocarcinoma (n = 14) arising in a background of intestinal metaplasia. A CK7+ CK20- immunophenotype was demonstrated in 27 of 30 (90%) patients with Barrett's-related oesophageal adenocarcinoma and only three of 14 (21%) gastric adenocarcinomas. The sensitivity, specificity and positive predictive value of a CK7+/20- immunophenotype for a diagnosis of Barrett's-related oesophageal adenocarcinoma was 90%, 79%, and 90%, respectively. CONCLUSIONS: A CK7+/20- tumour immunophenotype is associated with Barrett's-related oesophageal adenocarcinoma and may be useful in accurate tumour classification, thus facilitating improving epidemiological evaluation of tumours at the oesophagogastric junction.

Adenocarcinoma↗
PubMed2001

Immunohistochemical analysis of anaplastic lymphoma kinase expression in deep soft tissue calcifying fibrous pseudotumor: evidence of a late sclerosing stage of inflammatory myofibroblastic tumor?

Calcifying fibrous pseudotumor (CFT) is a rare benign soft tissue lesion composed of dense hyalinized fibrous tissue containing bland spindle-shaped cells admixed with a lymphoplasmacytic infiltrate and foci of dystrophic and often psammomatous calcifications. It has been suggested that CFT represents a late sclerosing stage of inflammatory myofibroblastic tumor (IMT). Recently, clonal cytogenetic abnormalities involving the anaplastic lymphoma kinase (ALK) gene on chromosome 2p have been identified in IMT, particularly those arising in deep soft tissue sites. We evaluated seven cases of deep soft tissue CFT diagnosed at the Cleveland Clinic Foundation and the University of Florida with available paraffin-embedded blocks using a monoclonal antibody to ALK (Dako, Carpenteria, CA) and a modified avidin-biotin complex method. The cohort included six women and one man with a median age at diagnosis of 43 years (range, 26 to 67 years). Sites of CFT included mesentery (3), peritoneum (1), omentum (1), serosa of small bowel (1), and anterior mediastinum (1). Immunohistochemically, only one case showed focal staining for ALK. The remaining six cases were negative, with appropriate positive and negative control staining. In conclusion, unlike IMT, CFT in deep soft tissue locations rarely expresses ALK by immunohistochemistry, suggesting that CFT is a different clinicopathologic entity than IMT, as opposed to representing a "burned out" IMT. Ann Diagn Pathol 5:10-14, 2001.

Adult↗
PubMed2001

Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation.

Morphologic assessment of dysplasia in Barrett esophagus, despite limitations, remains the basis of treatment. We rigorously tested modified 1988 criteria, assessing intraobserver and interobserver reproducibility. Participants submitted slides of Barrett mucosa negative (BE) and indefinite (IND) for dysplasia, with low-grade dysplasia (LGD) and high-grade dysplasia (HGD), and with carcinoma. Two hundred fifty slides were divided into 2 groups. The first 125 slides were reviewed, without knowledge of the prior diagnoses, on 2 occasions by 12 gastrointestinal pathologists without prior discussion of criteria. Results were analyzed by kappa statistics, which correct for agreement by chance. A consensus meeting was then held, establishing, by group review of the index 125 slides, the criteria outlined herein. The second 125-slide set was then reviewed twice by each of the same 12 pathologists, and follow-up kappa statistics were calculated. When statistical analysis was performed using 2 broad diagnostic categories (BE, IND, and LG v HG and carcinoma), intraobserver agreement was near perfect both before and after the consensus meeting (mean kappa = 0.82 and 0.80). Interobserver agreement was substantial (kappa = 0.66) and improved after the consensus meeting (kappa = 0.70; P =.02). When statistical analysis was performed using 4 clinically relevant separations (BE; IND and LGD; HGD; carcinoma), mean intraobserver kappa improved from 0.64 to 0.68 (both substantial) after the consensus meeting, and mean interobserver kappa improved from 0.43 to 0.46 (both moderate agreement). When statistical analysis was performed using 4 diagnostic categories that required distinction between LGD and IND (BE; IND; LGD; HGD and carcinoma), the pre-consensus meeting mean intraobserver kappa was 0.60 (substantial agreement), improving to 0.65 after the meeting (P <.05). Interobserver agreement was poorer, with premeeting and postmeeting mean values unchanged (kappa = 0.43 at both times). Interobserver agreement was substantial for HGD/carcinoma (kappa = 0.65), moderate to substantial for BE (kappa = 0.58), fair for LGD (kappa = 0.32), and slight for IND (kappa = 0.15). The intraobserver reproducibility for the diagnosis of dysplasia in BE was substantial. Interobserver reproducibility was substantial at the ends of the spectrum (BE and HG/carcinoma) but slight for IND. Both intraobserver and interobserver variation improved overall after the application of a modified grading system developed at a consensus conference but not in separation of BE, IND, and LGD. The criteria used by the group are presented. HUM PATHOL 32:368-978.

Algorithms↗
PubMed2001

Dysplasia as a predictive marker for invasive carcinoma in Barrett esophagus: a follow-up study based on 138 cases from a diagnostic variability study.

The objective of endoscopic surveillance in Barrett esophagus (BE) is to assess the risk of subsequent development of invasive carcinoma. Criteria for morphologic evaluation of dysplasia, the presumed precursor lesion, have been established, although there are surprisingly few data in the literature correlating biopsy diagnosis of dysplasia with outcome. We collected follow-up information on 138 patients with BE whose initial endoscopic biopsy specimens had been selected for submission in an interobserver variability study performed by 12 pathologists with special interest in gastrointestinal pathology and reviewed blindly twice each by all the participants. Cases were scored as BE with no dysplasia, atypia indefinite for dysplasia (IND), low-grade dysplasia (LGD), high-grade dysplasia (HGD), intramucosal carcinoma, and frankly invasive carcinoma, thus generating 24 scores on each biopsy specimen. Clinical follow-up was obtained and correlated with both the submitting diagnoses and majority diagnoses. Kaplan-Meier statistics were used to compare both the submitting and majority diagnoses with outcome using detection or documentation of invasive carcinoma as the endpoint. Using the submitting diagnoses, no invasive carcinomas were detected in 44 cases diagnosed as BE (median follow-up, 38.5 months). Carcinomas were detected in 4 of 22 (18%) cases submitted as IND (median progression-free survival of 62 months), in 4 of 25 (15%) cases of LGD (median progression-free survival of 60 months), in 20 of 33 cases of HGD (median progression-free survival, 8 months), and all 13 (100%) cases submitted as adenocarcinoma. Grade on initial biopsy correlated significantly with progression to invasive carcinoma (log-rank P =.0001). Majority diagnosis was achieved in 99 of the cases. Using the majority diagnoses, no invasive carcinomas were found in 50 cases of BE (median follow-up, 48 months), and carcinomas were detected in 1 of 7 (14%) IND cases (80% progression-free survival at 2 months), 3 of 15 (20%) LGD (median progression-free survival, 60 months), 9 of 15 (60%) HGD (median progression-free survival, 7 months), and all 12 (100%) carcinoma. Initial grading again correlated significantly with progression to invasive carcinoma (log-rank P =.0001). However, there were 39 cases without a majority diagnosis. Among these, no carcinomas developed in 8 cases with an average score between BE and IND. Carcinomas were detected in 9 of 21 (43%) cases with an average score between IND and LGD, and 7 of 10 (70%) cases with an average score between LGD and HGD. There were ulcers in 8 of 39 cases (20%) of the "no-majority" group and in 13 of 99 (13%) of the majority cases. Of 21 total ulcerated cases, cancer was demonstrated in 15 (71%) of these on follow-up. These data support combining the IND and LGD categories for surveillance purposes. Cases without dysplasia may be followed up conservatively. The data obtained from submitted diagnoses as opposed to those from blind review suggest that knowledge of the clinical findings aids in diagnosis. The data also support the assertion that HGD is strongly associated with invasive carcinoma. Rebiopsy of ulcerated areas should be considered because they may harbor malignancy. Histologic grading of dysplasia using established criteria is a powerful prognosticator in BE. HUM PATHOL 32:379-388.

Adolescent↗
PubMed2001

N1 esophageal carcinoma: the importance of staging and downstaging.

OBJECTIVE: To evaluate the effects of clinical staging and downstaging by induction chemoradiation therapy in patients with N1 esophageal carcinoma. METHODS: Sixty-nine consecutive patients with regional lymph node metastases (cN1) according to clinical staging received induction therapy before surgery. These were compared to 75 patients both clinically and pathologically N1 (cN1/pN1) who underwent surgery without induction therapy and 79 patients clinically and pathologically not N1 (cN0/pN0) who underwent surgery without induction therapy. Analyses focused on survival and the cost and benefit of therapy. RESULTS: For comparison, the extremes of 5-year survival were 69% for cN0/pN0 patients who underwent surgery alone and 12% for cN1/pN1 patients who underwent surgery alone. Of 69 patients who received induction therapy, 37 were pN0 at resection (downstaged); they had an intermediate survival of 37% at 5 years. Those patients not downstaged with induction therapy had a 12% 5-year survival, similar to patients with cN1/pN1 who underwent surgery alone. After adjusting for the strongest predictors of poor outcome, pN1, and increasing N1 burden, a modest increased risk of death after induction therapy was identified. However, this cost of induction therapy was more than counterbalanced by the benefit of improved survival of downstaging to pN0. CONCLUSIONS: (1) pN1 is the strongest determinant of poor outcome. (2) cN1 patients who are downstaged by induction chemoradiation therapy to pN0 have an intermediate outcome. (3) cN1 patients who are not downstaged by induction therapy have a poor outcome.

Adenocarcinoma↗
PubMed2001

Superficial adenocarcinoma of the esophagus.

OBJECTIVE: Experience with treatment and outcome of superficial adenocarcinoma of the esophagus is limited. The purpose of this study was to evaluate the results of surgical management and identify predictors of survival. METHODS: Between September 1985 and December 1999, 122 patients underwent resection. Eighty-nine percent were men (mean age 63 +/- 10 years; range 35-83 years). Sixty (49%) patients were in endoscopic surveillance programs and 48 (39%) had the preoperative diagnosis of high-grade dysplasia. Forced expiratory volume in 1 second was less than 2 L in 12 (12%). Seventy-five (61%) patients underwent transhiatal esophagectomy. Pathologic stage was N1 in 8 (7%). Pulmonary complications necessitating reintubation (respiratory failure) occurred in 10 (8%) patients. Time-related survival models were developed for decision-making (preoperative), prognosis (operative), and hospital care (postoperative). RESULTS: Operative mortality was 2.5%. Survival at 1, 5, and 10 years was 89%, 77%, and 68%. Preoperative decision-making factors associated with ideal outcome were 1-second forced expiratory volume of more than 2 L, surveillance, preoperative diagnosis of high-grade dysplasia, and planned transhiatal esophagectomy. Prognosis was decreased in younger patients and in those with N1 disease. Postoperative respiratory failure increased mortality. CONCLUSIONS: Surgery is the treatment of choice for superficial adenocarcinoma of the esophagus. The ideal patient has a preoperative diagnosis of high-grade dysplasia found at surveillance, good pulmonary function, and undergoes a transhiatal esophagectomy. Discovery of N1 disease or development of postoperative respiratory failure reduces the benefits of surgery.

Adenocarcinoma↗
PubMed2001

Myofibrosarcoma: a clinicopathologic study.

The concept of soft tissue sarcomas composed predominantly of myofibroblasts has been controversial. We examined a series of such lesions of low- and intermediate-grade malignancy to further define their clinical and pathologic features. Histologic appearances of four cases diagnosed as myofibrosarcoma by electron microscopy were reviewed. Eleven additional cases with similar morphology were then identified from 249 tumors originally indexed as fibrosarcoma. Electron microscopy was performed on five of these, and immunohistochemistry was carried out on all cases for which material was available. There were 11 men and 4 women aged 33 to 73 years (median, 54 yrs; mean, 53 yrs). Lesions mainly involved the head and neck, extremities, and trunk and ranged in size from 1.5 to 12 cm. The tumors were composed of bland or pleomorphic stellate to spindled cells with eosinophilic cytoplasm and tapered nuclei in a collagenous stroma; 10 were grade 1 and five were grade 2. All sarcomas displayed fascicular or storiform patterns, and some of the grade 1 lesions superficially mimicked nodular fasciitis. Electron microscopy of nine cases showed myofibroblastic differentiation, and immunohistochemistry showed smooth muscle actin in 13 of 15 cases, muscle-specific actin in 7 of 9, desmin in 6 of 14, and cytokeratin in 0 of 11. Four of nine grade 1 and three of four grade 2 tumors recurred (one twice), and one grade 2 tumor metastasized to the lungs. Myofibrosarcomas are indolent low-grade or occasionally aggressive intermediate-grade sarcomas which can be recognized by light microscopy. Their clinical importance lies in the resemblance, particularly of low-grade examples, to reactive or pseudosarcomatous conditions.

Adult↗
PubMed2001

Expression of Fli-1, a nuclear transcription factor, distinguishes vascular neoplasms from potential mimics.

Fli-1 protein, a member of the ETS family of DNAbinding transcription factors, is involved in cellular proliferation and tumorigenesis. Approximately 90% of Ewing's sarcoma/primitive neuroectodermal tumors (ES/PNET) have a specific translocation, t(11;22)(q24;q12), which results in fusion of EWS to Fli-1, and production of an EWS-Fli-1 fusion protein. We have recently shown that immunohistochemistry for the carboxy terminal of Fli-1 protein is sensitive and highly specific for the diagnosis of ES/PNET. In our earlier study we noted that among normal tissues only endothelial cells and small lymphocytes expressed Fli-1. Fli-1 expression in vascular neoplasms has not been previously studied. Formalin-fixed paraffin-embedded tissue from 54 vascular tumors and 75 nonvascular tumors were immunostained for Fli-1 (1:120, Sc 356, Santa Cruz Biotechnology, Santa Cruz, CA), after steam heat-induced epitope retrieval. Only cases with >10% of cells showing nuclear staining were accepted as positive. Cases without positive internal controls (endothelium and small lymphocytes) were not scored. Positive internal controls were present in 122 of 129 cases (95%). One vascular tumor (Kaposi's sarcoma) and 7 nonvascular tumors (2 epithelioid sarcomas and 5 carcinomas) without internal controls were not scored. Fli-1 was expressed by 50 of 53 vascular tumors scored (94%), including 20 of 22 angiosarcomas, 11 of 12 hemangioendotheliomas, 7 of 7 hemangiomas, and 12 of 12 Kaposi's sarcomas. In contrast, Fli-1 expression was absent in the 68 nonvascular tumors scored (0 of 68), including 16 sarcomas, 7 melanomas, and 45 carcinomas. The results of this study strongly suggest a role for Fli-1 as a novel marker of both benign and malignant vascular tumors. The sensitivity (94%) and specificity (100%) of Fli-1 with regards to the cases evaluated in this study equal or exceed those of the established vascular markers, CD31, CD34, and von Willebrand factor. As the first nuclear, rather than cytoplasmic or membranous marker of endothelium, Fli-1 immunostaining also generally lacks cytoplasmic staining artifacts that are the result of endogenous peroxidases or biotin.

Biomarkers, Tumor↗
PubMed2001

Leiomyosarcoma of the paratesticular region: a clinicopathologic study.

The behavior of leiomyosarcoma (LMS) is site related, but there are limited data on such tumors presenting in the paratesticular region. Cases diagnosed as LMS of the paratesticular region from the files of three institutions were reviewed. Immunohistochemistry was performed in cases with available blocks, and follow-up information was obtained. From 31 cases originally diagnosed as LMS, 24 were retained after review. These were from men aged 34-86 years (mean 62 years; median 64 years) and involved the testicular tunica (10), spermatic cord (10), scrotal subcutis and dartos muscles (1 each), and the epididymis (1). Tumors ranged in size from 2-9 cm (mean 5 cm; median 4 cm). On immunohistochemical staining they expressed muscle-specific actin (13 of 14), smooth muscle actin (10 of 10), desmin (16 of 17), and CD34 (3 of 9); all of the latter three were strongly desmin-positive. Focal reactivity for cytokeratin (3 of 8) and S-100 protein (1 of 8) was seen. Follow-up information was available in 14 patients. Four (29%) had recurrences, in one case four times. Metastases to lymph nodes, lungs, or liver were seen in four patients (29%), of whom two had prior recurrences. Ten were alive with no evidence of disease (ANED), and four were dead of disease (DOD). Comparing outcome with tumor grade, all seven patients with grade 1 tumors (of whom two had recurrences) and all three with grade 2 tumors were ANED, whereas all four patients with grade 3 tumors were DOD. In summary, paratesticular LMSs are rare neoplasms. The majority in this site are low-grade, although high-grade lesions behave aggressively.

Adult↗
PubMed2001

Squamous mucosal alterations in esophagectomy specimens from patients with end-stage achalasia.

Achalasia is an esophageal motor disorder in which the primary morphologic changes are found in the myenteric plexus. However, a number of secondary alterations are characteristically found in esophagectomy specimens, including the mucosa. In addition, these patients are at increased risk of developing esophageal squamous cell carcinoma. We studied the squamous mucosal alterations in 35 esophagectomy specimens from patients with end-stage achalasia and compared them with those found in the squamous mucosa near the esophagogastric junction from pediatric autopsies (</=18 years) from patients with no known esophageal disease. A representative block was immunostained for p53 (DO7), CD3, and CD20. p53 immunoreactivity was graded as follows: 0 = no staining; 1+ = rare basal cell staining; 2+ = extensive basal cell staining; 3+ = suprabasilar staining. Intraepithelial lymphocyte counts were performed by counting five high power fields (HPF) and calculating an average/HPF. Ages of achalasia patients at esophagectomy ranged from 21 to 78 years (mean 56 years), including 20 men and 15 women. Disease duration ranged from 1 to 44 years (mean 17 years). In all cases the squamous mucosa from achalasia patients was markedly hyperplastic with papillomatosis and basal cell hyperplasia. p53 staining in the squamous mucosa from achalasia patients was significantly more common than in controls (32 of 35 [91%] vs 1 of 17 [6%]; p <0.05). In all achalasia cases CD3+ cells far outnumbered CD20+ cells. There was a significantly greater number of CD3+ cells in achalasia cases (range 32-239/HPF; mean 107/HPF) compared with controls (range 0.8-12/HPF; mean 6/HPF) (p <0.05). In conclusion, the squamous mucosa in esophagectomy specimens from patients with end-stage achalasia shows significant alterations including marked squamous hyperplasia, an increased frequency of p53 immunoreactivity, and increased numbers of CD3+ cells when compared with controls. These changes may be related to the increased risk of squamous cell carcinoma in these patients.

Adolescent↗