One-day or two-day procedure for sentinel node biopsy in melanoma?

PURPOSE: We compared the outcome of a 1-day and a 2-day sentinel node (SN) biopsy procedure, evaluated in terms of lymphoscintigraphic, surgical and pathological findings. METHODS: We studied 476 patients with melanoma from two melanoma centres using static scintigraphy and blue dye. A proportional odds model was used for statistical analysis. RESULTS: The number of SNs visualized at scintigraphy increased significantly with time from injection to scintigraphy and activity left in the patient at scintigraphy, and depended on the melanoma location. The number of SNs removed at surgery increased with the number of SNs visualized at scintigraphy and time from injection to surgery. The frequency of nodal metastasis increased with increasing thickness and Clark level of the melanoma, and was highest for two SNs visualized at scintigraphy. CONCLUSION: This study showed that early vs. late imaging and surgery do make a difference on the outcome of the SN procedure and confirmed the importance of the scintigraphic visualization of all true SNs.

Primary lymphoma of the lacrimal sac: an EORTC ophthalmic oncology task force study.

AIM: To define the clinical and histopathological characteristics of primary lacrimal sac lymphoma in a predominantly white population. METHODS: Specimens of lacrimal sac lymphoma and follow up data were solicited from members of the Ophthalmic Oncology Task Force of the European Organization for Research and Treatment of Cancer (EORTC) and the European Ophthalmic Pathology Society (EOPS). Specimens were stained with haematoxylin and eosin and an immunohistochemical panel against leucocyte antigens was applied. Diagnosis was reached by consensus of five experienced pathologists according to the World Health Organization classification system. The histopathological findings were correlated with the clinical data. RESULTS: Of 15 primary lacrimal sac lymphomas, five (33%) were diffuse large B cell lymphoma (DLBCL), five (33%) were extranodal marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT lymphoma), three were classified as "transitional MALT lymphoma," being in transition from MALT lymphoma to DLBCL, and two were unclassified B cell lymphomas. Nine of the patients were female, and the median age at the time of diagnosis was 71 years (range 45-95 years). The most frequent presenting symptoms were epiphora (85%), swelling in the region of the lacrimal sac (79%), and dacryocystitis (21%). All but one patient presented in stage I. Systemic spread occurred in three of nine patients (33%). The 5 year overall survival was 65%. CONCLUSIONS: DLBCL and MALT lymphoma are equally common in the lacrimal sac in contrast with the remaining periorbital and/or orbital region where MALT lymphoma predominates.

Epstein-Barr positive T-cell lymphoma in the ocular region.

PURPOSE: To present two cases of rapidly growing tumors in the ocular adnexa. Both tumors were Epstein-Barr virus (EBV) positive peripheral T-cell lymphoma. METHODS: Case 1 was a 60-year-old man with a non-tender ulcerating tumor involving the lateral third of both upper and lower right eyelid. Case 2 was a 55-year-old man with a swelling of the left eyelid expanding cranially and dislocating the left eye, resulting in proptosis and diplopia. Both patients underwent incisional biopsy that did not disclose the malignant nature of the tumors. Clinical evaluation resulted in suspicion of malignancy and surgical excision was performed. RESULTS: The tumors were found to be consistent with EBV-positive peripheral T-cell lymphoma. CONCLUSIONS: Peripheral T-cell lymphoma is uncommon but a diagnosis to be considered in a patient with a tumorous lesion in the eye region. Furthermore, peripheral T-cell lymphoma may be EBV-positive.

Loop diathermy or laser excisional conization for cervical intraepithelial neoplasia.

BACKGROUND: Cervical intraepithelial neoplasia (CIN) can be managed by ablative or excisional procedures. We have compared the excision time, effectiveness, and safety of loop diathermy (loop) against laser conization. METHODS: In a prospective study in two hospital departments 222 women were randomized to loop or laser conization. Data were collected by questionnaires after operation and at two follow-up examinations. RESULTS: At department A (122 women), two physicians performed 27% of the loop and 35% of the laser excisions; at department B (100 women), the corresponding figures were 69% and 59%. Loop was quicker than laser conization in both departments (median 3-4 min versus 10-20 min), while laser conization was more time consuming in department A (median A/B = 20/10 min). Peroperative bleeding dominated during the laser procedure in both departments and complicated the loop procedure more frequently in department A. Postoperative bleeding occurred with equal frequency in the four groups (41.8%, 52.7%, 59.2%, 64.7%). At both departments, bleeding for more than two weeks was reported twice as often after laser conization (A:13.8%, B:24.2%), when compared to loop excision (A:7.1%, B:13.7%). Residual CIN was found in all of three re-conizations and in one of eight hysterectomy specimens. CONCLUSIONS: Loop was quicker than laser excision, per- and postoperative bleeding diminished, and the success rates were comparable. Physicians mastered Loop excision after a few attempts. However, the results improved, when performed by a restricted number of physicians. Histological incomplete excision indicates close colposcopic and cytologic follow-up to identify residual CIN.

Fatal virus-associated hemophagocytic syndrome associated with coexistent chronic active hepatitis B and acute hepatitis C virus infection.

A 28-year-old man was admitted to our department with intermittent fever, hepatosplenomegaly and pancytopenia. Liver parameters and serum ferritin were markedly elevated. Bone marrow biopsy showed hypocellularity, histiocytic hyperplasia, and hemophagocytosis consistent with a virus-associated hemophagocytic syndrome (VAHS). There was serological evidence of chronic active hepatitis B and acute hepatitis C virus infection. The patient died despite aggressive immunosuppressive and supportive treatment. Autopsy revealed signs of acute viral hepatitis with cholestasis. Histiocytes engaged in hemophagocytosis were observed in bone marrow and spleen. The condition was interpreted as VAHS associated with chronic active hepatitis B and acute hepatitis C virus infection. To our knowledge this is the first report of a hemophagocytic syndrome in that setting.

[Sentinel node diagnostics in malignant melanoma]. / "Sentinel node"-diagnostik ved malignt melanom.

New trial have shown that immediate regional lymph node dissection offers increased survival in patients with regional lymph node metastases only. Introduction of isotope technique to identify the first node, the sentinel node (SN), receiving lymph from a tumour area has made it possible to avoid node dissection in SN metastasis negative patients. The feasibility of the technique is illustrated by to examples.

Expression of polypeptide GalNAc-transferases in stratified epithelia and squamous cell carcinomas: immunohistological evaluation using monoclonal antibodies to three members of the GalNAc-transferase family.

Mucin-type O-glycosylation is initiated by a large family of UDP-GalNAc: polypeptide N -acetyl-galactosaminyltransferases (GalNAc-transferases). Individual GalNAc-transferases appear to have different functions and Northern analysis indicates that they are differently expressed in different organs. This suggests that O-glycosylation may vary with the repertoire of GalNAc-transferases expressed in a given cell. In order to study the repertoire of GalNAc-transferases in situ in tissues and changes in tumors, we have generated a panel of monoclonal antibodies (MAbs) with well defined specificity for human GalNAc-T1, -T2, and -T3. Application of this panel of novel antibodies revealed that GalNAc- transferases are differentially expressed in different cell lines, in spermatozoa, and in oral mucosa and carcinomas. For example, GalNAc-T1 and -T2 but not -T3 were highly expressed in WI38 cells, and GalNAc-T3 but not GalNAc-T1 or -T2 was expressed in spermatozoa. The expression patterns in normal oral mucosa were found to vary with cell differentiation, and for GalNAc-T2 and -T3 this was reflected in oral squamous cell carcinomas. The expression pattern of GalNAc-T1 was on the other hand changed in tumors to either total loss or expression in cytological poorly differentiated tumor cells, where the normal undifferentiated cells lacked expression. These results demonstrate that the repertoire of GalNAc-transferases is different in different cell types and vary with cellular differentiation, and malignant transformation. The implication of this is not yet fully understood, but it suggests that specific changes in sites of O-glycosylation of proteins may occur as a result of changes in the repertoire of GalNAc-transferases.

BEAM+autologous stem cell transplantation in malignant lymphoma: 100 consecutive transplants in a single centre. Efficacy, toxicity and engraftment in relation to stem-cell source and previous treatment.

One hundred consecutive patients with malignant lymphoma treated with high-dose chemotherapy and autologous stem cell transplantation, followed at least 1 yr post-transplant, are reported, 68 with non-Hodgkin's lymphoma and 32 with Hodgkin's disease. At transplant, 23 patients were in first remission, 69 in later chemosensitive disease and 8 were chemotherapy resistant. Based on previous treatment and stem-cell source, the patients were subdivided into 3 cohorts: BMT1: bone-marrow harvest and transplant after > or =3 treatment regimens (38 patients); BMT2: bone marrow harvest and transplant after less than 3 treatment regimens (24 patients); PBSCT: peripheral-blood stem cell transplant (38 patients, 5 of these with CD34+ cell selected PBSC). The 4-yr survival and progression-free survival of all patients was 45 and 40%, respectively. Forty-one patients have died, 27 of lymphoma, evenly distributed in the cohorts. Fourteen treatment-related deaths occurred, 13 of these in the BMT1 cohort, significantly more than in the other cohorts (p=0.001). In univariate survival analysis cohort, age, disease status at transplant and number of previous treatment regimens were significant. In multivariate survival analysis cohort, age and sex were independently significant, women having a shorter survival. The patients transplanted with unselected PBSC had significantly shorter duration of pancytopenia and hospital stay than the otherwise comparable BMT2 patients, but their progression-free survival was identical. We confirm that high-dose therapy with autologous stem cell transplant from blood or bone marrow in not-too-heavily pretreated patients is a safe procedure but will cure only half the patients.

Combined bilateral submandibular and sublingual swelling, macroglossus, and carpal tunnel syndrome caused by light chain amyloidosis.

Three cases of light chain kappa amyloidosis in multiple myeloma patients are described with remarkable involvement of the tongue and swelling of the sublingual and submandibular regions, and without signs of nephropathy despite Bence Jones kappa proteinuria. All three patients had carpal tunnel syndrome at the beginning of their disease course and only moderate gastrointestinal involvement. Primarily for prognostic reasons, amyloidosis should be suspected in such cases, even in the presence of these highly unusual manifestations, and the diagnosis should be confirmed by unambigously-positive biopsies.

Carcinomas occurring in papillomas of the nasal septum associated with human papilloma virus (HPV).

Carcinomas arising in pre-existing sinonasal papillomas of the nasal septum are rare. To our knowledge only one case has been reported. We report two cases of carcinomas occurring in septal papillomas. In the first case a carcinoma developed in an exophytic papilloma 16 years after the first operation for a papilloma. In the second case a carcinoma was present at the first presentation within an inverted papilloma, and a metastasis had also developed. In the first case HPV type 6/11 was demonstrated by in-situ hybridisation and PCR in the original papilloma as well as in the recurrent papilloma and in the carcinoma. In the second case HPV type 18 was found in the nasal lesion as well as in the metastasis. All samples were examined for Epstein-Barr virus (EBV) by PCR, but with negative results. We believe that case one is the first reported case of carcinomatous transformation within an exophytic septal papilloma.

The estrogen receptor expression in the male rabbit urethra and prostate following castration.

The influence of castration on estrogen receptor (ER) expression in the male rabbit prostate and urethra, was investigated immunohistochemically and biochemically in 18 mature male, rabbits 14 days after bilateral orchiectomy, and in 15 controls. Immunohistochemical scores of ER were increased significantly in the prostatic stroma and the urethral submucosa (p < 0.05 Mann-Whitney), while the increase in the urothelium was not significant. Biochemically, the ER content was 87.4 +/- 42.6 f mol/mg protein in the normal prostate, and 190.0 +/- 28.0 f mol/mg protein following castration. The corresponding values for the posterior urethra were 228.3 +/- 43.2 f mol/mg protein and 354.9 +/- 60.1 f mol/mg protein. In both cases the increase was not significant. We conclude, that ERs in the prostate and the urethra of the male rabbit can be modified by hormonal manipulation. ERs may therefore be functionally active and not rudimentary.

Blood group antigens in transitional cell tumours of the urinary bladder. An immunohistochemical study.

Patients presenting histologically identical non-invasive tumours of the urinary bladder suffer a variable unpredictable clinical course, making the identification of prognostic markers relevant in the clinical setting. Recent histochemical studies have demonstrated that changes in cell surface carbohydrates during malignant transformation involve the blood group antigens. These oligosaccharides, initially defined on erythrocytes, are widely distributed in human tissue including human urothelium. This study was conducted in order to evaluate the prognostic value of blood group antigen determination in superficial bladder cancer. The aims of the present study were: 1. To standardize the immunohistochemical staining technique for blood group antigens, 2. To investigate the pattern of blood group antigen expression in non-neoplastic urothelium, the genetic heterogeneity, 3. To examine changes in the blood group antigen expression in bladder cancer, and 4. to assess the prognostic value of blood group antigen expression in superficial bladder cancers of morphological similar appearance. The ABH, Lewis, and Thomsen-Friedenreich (T) blood group antigens were studied by means of the Tween 20-modified indirect immunoperoxidase staining technique. Serial dilutions of antibodies and lectins were applied on dewaxed routinely processed tissue sections of normal ureters and transitional cell tumours. The reciprocal value of the highest dilution of antibody and lectin still giving staining defined the endpoint titer and allowed semiquantitative estimation of antigen content. In non-neoplastic urothelium the ABH, Lewis and T blood group antigens were heterogeneously expressed, and the expression correlated to the Lewis blood type. This indicates 1) a genetic regulated synthesis of ABH and Lewis blood group antigens similar to that operating in saliva, other secretions, epithelia, and erythrocytes, 2) a possible linkage between ABH-, Lewis-, and T antigen systems, if steric hindrance can be excluded. Based on the above findings in non-neoplastic urothelium the deviation in tumours from normal blood group antigen expression was quantified on a scale from 0 (normal) to 3 (total loss) for each antigen system separately. All scores were related to histological stage and grade suggesting a parallelism between morphological dedifferentiation and the degree of abnormal blood group expression. In superficial low grade tumours only A and Lewis a scores were related to prognosis. This held only true for patients with tumours of normal or nearly normal A and Lewis a antigen expression (scores 0 and 1), who had a favorable course as regards invasive recurrence and/or papillomatosis within 5 years. Prediction of an unfavorable outcome was not possible. Only a small number of superficial tumours exhibited normal blood group antigen expression.(ABSTRACT TRUNCATED AT 400 WORDS)

The distribution of estrogen receptors in the urinary tract of the male rabbit. An immunohistochemical and biochemical study.

The distribution of estrogen receptors (ER) in the urinary system in the male rabbit were investigated in 18 mature and healthy rabbits by immunohistochemical examination of tissue samples taken from renal pelvis, mid-ureter, bladder-top, posterior urethra and the prostate. ER were detected in 17 out of 18 cases in the urothelial lining and the subepithelial stromal cells of the posterior urethra; and in 15 out of 18 cases in prostatic stromal cells. ER was not found in bladder-top, mid-ureter or renal pelvis. Receptor determination in the isolated cytosolic and nuclear fraction, showed that the mean prostatic receptor density were 151.5 f mol/mg protein in the nuclear and 51.4 in the cytosolic fraction. The corresponding mean values obtained from the posterior urethra were 128.2 and 88.9 f mol/mg protein. We conclude, that ER can be demonstrated in the urinary system of the male rabbit, and these are restricted to the posterior urethra and the prostatic stromal tissue.

CEA and carbohydrate antigens in normal and neoplastic colon mucosa. An immunohistochemical study.

Antibodies raised against tumour-associated antigens have been assessed for tumour selectivity using an indirect immunohistochemical peroxidase staining of formalin-fixed, paraffin-embedded tissue from colon carcinomas, colon polyps and normal mucosa. The following antibodies were used: 1) Unabsorbed polyclonal antibody to carcinoembryonic antigen (poly-CEA). 2) Monoclonal antibodies to CEA (mabs 3851 and 27). 3) Monoclonal antibodies to protein-bound carbohydrates (mabs C 216 and C 242) or to lipid- and protein-bound carbohydrates (C 50 and 19-9). These antibodies had been produced by hybridization of lymphocytes from mice, immunized with colon carcinoma cell lines or colon cancer tissue. All antibodies were used in one concentration only, preselected by initial titration experiments. No antibody was completely tumour-specific, but four antibodies, mabs 3851, 27, C 216 and C 242, showed statistically significant tumour selectivity. Using these antibodies, respectively 19, 19, 19, and 18 of 20 colon cancer were stained compared with 3, 4, 4, and 8 of 15 specimens of colon mucosa from normal controls. An increased frequency of staining was also noted in dysplastic polyps (statistically significant using mabs 3851 and C 216) and in dysplastic mucosa adjacent to a tumour (statistically significant using mabs 3851 and 27). The staining frequency of normal colon mucosa in cases of colon cancer did not differ from that in the normal controls. Poly-CEA and the anti-ganglioside mabs C 50 and 19-9 revealed no tumour selectivity. A pronounced goblet cell staining was seen using C 50, C 242 and 19-9.

Thomsen-Friedenreich-related antigen in non-neoplastic ureter urothelium and transitional cell tumours of the urinary bladder. An immunohistochemical study employing the monoclonal antibody 49H.8.

This study, which is part of a larger immunohistochemical investigation of blood-group antigens in non-neoplastic urothelium and bladder cancer, reports our findings on the expression of an antigen related to the cryptic Thomsen-Friedenreich antigen (beta Gal 1-3 GalNAc) of erythrocytes. De-waxed sections of 19 ureters and of 93 transitional cell tumours, either untreated or pretreated with neuraminidase, were subjected to an indirect immunoperoxidase staining, employing the monoclonal antibody 49H.8. Staining results were compared to Lewis-secretor types, morphology, and in tumours to the clinical course as regards recurrence rate and the development of either stroma invasive recurrence or papillomatosis as well. Ureters not subjected to neuraminidase were unstained, whereas urothelium in 12 of 19 ureters subjected to neuraminidase showed staining. Serial dilution of antibody disclosed quantitative differences related to the Lewis-secretor types. Lea+b- urothelium, i.e., non-secretor urothelium, had the highest end-point titers. Endothelium was unstained. Thirty-six of the 93 tumours showed staining without prior neuraminidase treatment, 31 showed staining after neuraminidase treatment only, while 26 were unstained. Staining correlated with the pathological stage and grade (p less than 0.05), but not with the clinical course (p greater than 0.05). The results do not support previous observations on the prognostic value of Thomsen-Friedenreich antigen determination in superficial bladder cancer.

Lewis a antigen in transitional cell tumors of the urinary bladder.

The failure of A,B,H antigens as prognostic parameters in noninvasive bladder cancer of blood group O individuals, who constitute 44% of the population, encouraged the evaluation of the closely related Lewis a antigen. Ninety-three tumors of the urinary bladder were stained employing the Tween 20 (Merck)-modified immunoperoxidase staining technique and serial dilution of monoclonal anti-Lewis a antibodies. On the basis of recent findings in non-neoplastic ureter urothelium of erythrocyte Lea+b-, Lea-b+, and Lea-b- individuals, alterations in tumors, except eight from Lea-b- individuals, were quantified on a scale from 0 (normal) to 3 (total loss). Scores were related to the pathologic stage and grade (P less than 0.01), and, in stage Pa tumors, to the clinical course: recurrence rate (P less than 0.10), stroma invasive recurrence, and/or papillomatosis (P less than 0.05). Although further studies are needed the current study points to Lewis a antigen determination as an advantageous prognostic tool in stage Pa tumors of the urinary bladder of Lea-b+ and Lea+b- individuals, who, together, constitute 94% of the population.

A, B, H antigen expression in transitional cell carcinomas of the urinary bladder.

The prognostic value of A, B, H blood group antigen determination in superficial bladder cancer is unclear. Recent immunohistochemical studies employing monoclonal antibodies and Ulex Europaeus Agglutinin I (UEA-I) (Vector) have shown that A, B, H detectability and distribution in non-neoplastic urothelium are influenced by methodologic factors and, most importantly, by the secretor status. The authors investigated the A, B, H antigen in 93 tumors of the urinary bladder (78 secretors, 15 nonsecretors) and semiquantified the alterations from the expected normal expression on a scale from 0 to 3. Four O saliva nonsecretors as expected showed no staining and were excluded. Eighty tumors showed abnormal A, B, H expression and in 37 of these, A, B, H antigens were not detected. Tumors of A and O individuals showed statistically different reactivities, probably related to differences in the specificity of the employed A- and H-reagents. A, B, H expression was influenced by stage and grade (P less than 0.05, P less than 0.10) and was correlated to the clinical course of A but not O patients. These results, suggesting that alterations in the A, B, H expression occur early in the neoplastic development and follow the synthetic pathways in an opposite direction, emphasize that reagents recognizing blood group precursor substances, common to all individuals irrespective of the ABO and saliva secretor types, may increase the prognostic accuracy of blood group antigen determination in bladder cancer.

Semiquantitative immunohistochemical evaluation of H-antigen expression in human ureters of different ABO- and Lewis types.

A study was undertaken to obtain baseline information for future studies of H-antigen expression in urothelial tumors. The influence of ABO- and Lewis genes on H-antigen expression in human ureters was investigated. Thirty two ureters of different ABO- and Lewis types were stained by the Tween 20-modified immunoperoxidase staining technique using Ulex europaeus agglutinin I (32 cases) and two monoclonal anti-H antibodies (10 cases). Ureters from A and AB individuals were also stained using monoclonal anti-A and Dolichos biflorus agglutinin (14 cases). The H-antigen expression in endothelium of all cases and in urothelium of Lea-b+ and Lea-b- individuals was correlated to ABO blood type. H antigen was never detected in urothelium of Lea+b- individuals. Endothelial H-antigen expression was not influenced by the Lewis types. In A and AB individuals, urothelial and endothelial H- and A-antigen and Dolichos biflorus reactivities were mainly insignificantly related, with correlation coefficients ranging numerically from 0.10 to 0.72. The study stresses the importance of relating blood group antigen H expression in urothelial tumors to the ABO-, Lewis, and secretors types of the individual.

Immunohistochemical demonstration and localization of Lewis a and Lewis b determinants in human urothelium.

In order to obtain baseline information about Lewis antigen expression in human urothelium in order that changes during malignant transformation can be evaluated, urothelium from eight individuals of known erythrocyte Lewis types were stained by a Tween-modified indirect immunoperoxidase staining technique using goat antibodies directed toward the Lewis a and Lewis b determinants and mouse monoclonal antibodies directed toward the Lewis a determinant in serial dilutions. To evaluate the value of the method for tissue Lewis typing, eleven ureters from individuals of unknown erythrocyte Lewis types were stained using goat antibodies. The Lewis antigens were located on the cell membranes and in the cytoplasm of urothelial cells. Goat antibodies identified Lea-b-, Lea+b+, and Lea+b- urothelium. Monoclonal antibodies identified urothelium with both low and high Lewis a antigen expression as well as urothelium with no Lewis a antigen expression. Urothelial Lewis antigen expression correlated with erythrocyte Lewis types in Lea-b+ and Lea+b- individuals. In Lea-b- individuals Lewis determinants were either not detected or were expressed similarly to Lea-b+ individuals. Urothelial Lewis typing were doubtful in two out of the eleven ureters examined. The results imply that knowledge about erythrocyte Lewis type or normal tissue Lewis antigen expression is necessary for the immunohistochemical evaluation of changes in Lewis antigen expression in urothelial tumors.