Is the sentinel lymph node pathology protocol in breast cancer patients associated with the risk of regional recurrence?

BACKGROUND: Internationally, there is no consensus on the pathology protocol to be used to examine the sentinel lymph node (SN) in breast cancer patients. Previously, we reported that ultra-staging led to more axillary lymph node dissections (ALND). The question was, whether ultra-staging is effective in reducing the risk of regional relapse. METHODS: From January 2002 to July 2003, 541 patients from 4 hospitals were prospectively registered when they underwent a SN biopsy. In hospitals A, B, and C, 3 levels of the SN were examined pathologically, whereas in hospital D at least 7 additional levels were examined. Patients with a positive SN, including isolated tumor cells, underwent an ALND. This analysis focuses on the 341 patients with a negative SN. Primary endpoint was 5-year regional recurrence rate. RESULTS: In hospital D 34% of the patients had a negative SN as compared to 71% in hospitals A, B, and C combined (p < 0.001). At 5 years follow-up, 9 (2.6%) patients had developed a regional lymph node relapse. In hospital D none of the patients had a regional recurrence, as compared to 9 (2.9%) cases of recurrence in hospitals A, B, and C. CONCLUSION: The less intensified SN pathology protocol appeared to be associated with a slightly increased risk of regional recurrence. The absolute risk was still less than 3%, and does not seem to justify the intensified SN pathology protocol of hospital D.

Axillary recurrences after negative sentinel lymph node biopsy under local anaesthesia for breast cancer: a follow-up study after 5 years.

INTRODUCTION: Sentinel lymph node biopsy (SLNB) is accepted as a standard surgical staging procedure for determining the tumour status of the regional lymph nodes. Until September 2000 we performed SLNB in general anaesthesia. Since 1999, after validation of the SLNB concept, axillary dissection was omitted in SLN-negative patients. This study presents our data after SLNB under local anaesthesia after a follow-up of at least 5 years. MATERIALS AND METHODS: Between September 2000 and May 2003, 356 SLNBs were performed under local anaesthesia without sedation in patients with proven breast cancer (T4-tumours and small in situ carcinomas excluded) and without clinically or ultrasound guided cytological evidence of axillary node involvement. Lymphatic mapping and SLN identification were performed through the combination of blue dye and 99m Tc-nanocolloid. All positive SLNs were followed by an axillary dissection up to level three. SLN-negative patients were followed without axillary clearance. RESULTS: In 353/356 SLNBs at least one sentinel node was found. 254/353 SLNs were tumour free. After a median follow-up of 73 months loco-regional and distant events were encountered in 10/353 SLNBs. Four patients (SLN-negative) showed tumour localization in the residual breast or chest wall (1.1%). Three patients (SLN-negative) presented with supraclavicular metastases (0.8%). In three patients (one SLN-negative and two SLN-positive followed by ALND) an axillary recurrence was encountered (0.8%). CONCLUSION: This survey confirms the safety of the SLNB under local anaesthesia in selecting patients for axillary lymph node dissection in breast cancer.

Long-term survival of T1 and T2 lymph node-negative breast cancer patients according to Mitotic Activity Index: a population-based study.

Node-negative breast cancer patients have a relatively good prognosis, but eventually one-third will die of the disease. Thus, prognostic factors to identify the high-risk group among these patients are needed. We retrospectively determined the Mitotic Activity Index (MAI) for a large series of node-negative breast cancer patients (n = 468) with tumours smaller than 5 cm, who only received locoregional treatment. Patients were followed for up to 29 years; crude and relative survival were calculated, both univariate and multivariate. Relative survival differed significantly according to MAI (p = 0.05), the difference occurred in the first 5 years after diagnosis and remained constant thereafter. After adjustment, MAI still significantly affected relative survival (RER, 1.9; 95% CI, 1.1-3.5). Tumour size also increased the risk, but this was not statistically significant (RER, 1.5; 95% CI, 0.8-2.7). Survival of patients with a T1 tumour and MAI < 10 was similar to that for the general population in the first 5 years after diagnosis. In conclusion, MAI significantly predicted long-term survival for T1/T2N0 breast cancer. Adjuvant systemic therapy appears to have little benefit for node-negative breast cancer patients with a T1 tumour, regardless of the MAI. For those with a T2 tumour and a MAI > or = 10 systemic therapy might have reduced mortality. The need for close surveillance of node-negative breast cancer patients with a T1 tumour and MAI < 10 seems limited.

Ambulatory sentinel node biopsy under local anaesthesia for patients with early breast cancer.

AIMS: Sentinel lymph node biopsy (SLNB) may permit reliable identification of patients with axillary node involvement. The aim of this study was to report our experience with this procedure under local anaesthesia. METHODS: One hundred and sixty-two patients underwent a sentinel node procedure under local anaesthesia without sedation. The SLN was identified by (99m)Tc-nano-colloid and patent blue. Immediate histopathologic examination and immunohistochemistry was performed. Patients with positive SLNs proceded to axillary dissection under general anaesthesia. RESULTS: In all 162 patients the SLN ('s) were found using blue dye and gamma-probe. The SLN was positive in 55/162 patients (34%). Five of these were detected using immunohistochemistry only. CONCLUSIONS: A 100% detection rate of sentinel nodes in early breast cancer harvested under local anaesthesia was achieved without serious morbidity. This allows the surgeon to select preoperatively the treatment given to the patient.

Histological grading of papillary urothelial carcinoma of the bladder: prognostic value of the 1998 WHO/ISUP classification system and comparison with conventional grading systems.

AIM: To test the prognostic value of the 1998 WHO/ISUP (World Health Organisation/International Society of Urologic Pathology) consensus classification system in Ta papillary urothelial neoplasms of the bladder. METHODS: The histological slides of 322 patients with a primary Ta tumour were classified according to the consensus classification system, and recurrence free survival (RFS) and progression free survival (PFS) were assessed for a mean follow up period of 79 months. In the same patient group, the RFS and PFS rates for the 1973 WHO grading system and a low grade/high grade system were analysed. RESULTS: Recurrent tumours were seen in all categories of the 1998 WHO/ISUP classification system and five year RFS was not significantly different between the groups (p = 0.12). The five year PFS showed a small but significant difference (p = 0.04) between papillary neoplasms of low malignant potential (PNLMP) and high grade papillary urothelial carcinomas (HGPUCs). In the 1973 WHO classification, no significant difference was found in RFS and PFS between the different grades. In the low grade/high grade classification PFS was significantly better for low grade tumours (p = 0.01). CONCLUSION: The prognostic value of the 1998 WHO/ISUP classification system is limited to predicting PFS, especially between PNLMP and HGPUC. The prognostic value of this system over other grading systems is questionable.

Trends in breast cancer aggressiveness before the introduction of mass screening in southeastern Netherlands 1975-1989.

OBJECTIVE: The increased incidence of breast cancer in the southeastern Netherlands was accompanied by markedly improved relative survival and stable mortality. We investigated whether the average aggressiveness of tumors changed over time in a population-based study, before the introduction of mass screening. METHODS: The mitotic activity index (MAI) was determined retrospectively for 1051 consecutive patients diagnosed with invasive, non-metastatic breast cancer in 1975, 1981, 1988, and 1989. Trends over time, and effects of age, tumor size and lymph node status were examined by univariate and multivariate regressions. RESULTS: Age-adjusted incidence of low MAI tumors changed from 35/100,000 in 1975 to 45/100,000 in 1988-89, an increase of 30% (P = 0.01), the incidence of tumors with a high MAI increased about 20% (P = 0.28), from 25 to 29/100,000. For small tumors (T1) the odds for a high MAI was lower in 1981 (OR: 0.80; 95% CI: 0.37-1.73) and 1988-89 (OR: 0.66; 95% CI: 0.35-1.23) compared to 1975. Among T3 and T4 tumors the odds increased to 2.03 (95% Cl: 0.71-5.86) in 1981 and 2.16 (0.76-6.18) in 1988-89. CONCLUSION: Although the incidence of tumors with low aggressive potential increased, the incidence of high MAI tumors also increased. Stable breast cancer mortality rates in the face of increasing incidence rates during the period 1975-89 cannot be attributed solely to changes in tumor aggressiveness; early diagnosis and better treatment may also have contributed.

Abnormalities detected in metaphase chromosomes in bladder carcinoma: prognostic value and comparison with histopathological factors.

The objective of this study was to detect the incidence and prognostic value of chromosomal aberrations in metaphase chromosomes (hypodiploidy, hyperdiploidy and/or structural abnormalities) in Ta and T1 transitional cell carcinoma (TCC) of the bladder. Of 266 patients, the metaphase chromosomes of the primary tumour were studied using a direct microscopic analysis and classified into two categories: normal and abnormal. Recurrence and progression were prospectively recorded during a median follow-up period of 40 months and in a retrospective analysis compared with other prognostic factors. Chromosomal abnormalities were found in 48% of Ta tumours and in 92% of T1 tumours. In univariate analysis, chromosomal abnormalities were associated with recurrence-free survival ( P=0.03) and progression-free survival ( P=0.01). In multivariate analysis, chromosomal abnormalities (RR=1.98) and age (RR=0.64) were independent predictors of recurrence-free survival but not progression-free survival.

MIB-1 as a proliferative marker in transitional cell carcinoma of the bladder: clinical significance and comparison with other prognostic factors.

BACKGROUND: Staging and grading of transitional cell carcinoma of the bladder are generally viewed as indicators of prognosis and form the basis of therapy, but they do not predict outcome accurately. This study was designed to evaluate the value for predicting recurrence, progression, and survival of proliferation fraction in transitional cell carcinoma of the bladder determined by immunostaining of histopathologic specimens with the monoclonal antigen MIB-1. METHODS: In a prospectively followed group of 301 patients with transitional cell carcinoma of the bladder, formalin fixed tumor specimens were immunostained and the MIB-1 labeling index was determined. Crude survival, progression free survival, and recurrence free survival (for patients with Ta and T1 tumors) were assessed in univariate and multivariate analysis according to stage, grade, mitotic index of the tumor, and patient age. The median value of continuous variables was used as a cutoff point in statistical analysis. RESULTS: In univariate analysis there was a strong association between all included factors and crude survival, progression free survival, and recurrence free survival with a median follow-up period of 60 months. In multivariate analysis, crude survival and progression free survival were determined by stage (P = 0.0001) and age (P = 0.0001). Recurrence free survival for patients with Ta and T1 tumors was determined by MIB-1 labeling index (P = 0.0317), mitotic index (P = 0.0229), and age (P = 0.0001). CONCLUSIONS: MIB-1 immunostaining in transitional cell carcinoma of the bladder correlated well with grade, stage, and clinical outcome. In multivariate analysis, proliferation fraction had prognostic value in predicting recurrence free survival for patients with Ta and T1 tumors, whereas stage and age appeared to be predictors of progression free survival.

Trends in incidence and mortality rates for prostate cancer before and after prostate-specific antigen introduction. A registry-based study in southeastern Netherlands, 1971-1995.

The incidence of prostate cancer has increased considerably over the past two decades, partly due to the increased detection of subclinical cases. In southeastern Netherlands, a region of almost 1 million inhabitants with good access to specialised medical care, prostate-specific antigen (PSA) assays were not introduced until 1990, allowing us to investigate the nature of the increases in incidence. Age-adjusted (European Standardised Rate) and age-specific rates were calculated using incidence data from the population-based Eindhoven Cancer Registry and mortality data from Statistics Netherlands. The age-adjusted incidence, which increased from 36 per 100,000 in 1971 to 55 per 100,000 in 1989, included all grades as well as metastasised prostate cancer. The age-adjusted mortality mainly fluctuated in this period, but increased among men aged 55-64 years from 12 per 100,000 in 1980 to 25 per 100,000 in 1989. After 1990, the age-adjusted incidence further increased to 80 per 100,000 in 1995, the increase representing mainly low-grade localised prostate cancer, presumably due to increasing opportunistic PSA testing, especially after 1993. A real increase in incidence may have occurred before 1993. However, pending results of randomised trials, judicious application of PSA testing seems justifiable to avoid unnecessary intervention without reducing mortality.

Prognostic value of DNA ploidy using flow cytometry in 1301 breast cancer patients: results of the prospective Multicenter Morphometric Mammary Carcinoma Project.

The literature on breast cancer reports conflicting prognostic results with respect to DNA ploidy of flow cytometric DNA histograms. This might result from different DNA ploidy classification methods. Our study evaluated the prognostic power of DNA ploidy, using different classification methods, in a large prospective group (n = 1301) of breast cancer patients. Flow cytometric DNA histograms obtained from fresh frozen material were interpreted with use of a commercially available computer program. On the basis of the number of stemlines and the DNA Index, we classified the DNA ploidy by different methods. In all of the cases, the classification method "DNA diploid versus DNA nondiploid" provided the best prognostic significance for overall survival (OS) (Mantel-Cox (MC) = 5.4, P = .02; relative risk (RR) = 1.3, P = .05) and for disease-free survival (DFS) (MC = 11.8, P = .0006; RR = 1.3, P < .05). This was also true for the OS of the lymph node-positive (but not the lymph node-negative) subgroup (MC = 4.1, P = .04; RR = 1.3, P = .05). In subgroups classified on the basis of tumor size, DNA ploidy showed prognostic significance for DFS only in the subgroup of tumors smaller than 2 cm and larger than 5 cm. In multivariate analysis, DNA ploidy showed no additional prognostic power to lymph node status and tumor size. The classification "DNA diploid versus DNA nondiploid" was mostly consistent with respect to prognostic power for OS and DFS, especially in small or lymph node-positive tumors. The RR of DNA nondiploid patients was only marginally higher, however, so large study groups are required to reach statistical significance. This could partly explain the disagreements in the literature. Therefore, DNA ploidy seems to be of little clinical importance in breast cancer patients, compared with other prognostic parameters.

Prognostic implications of different cell cycle analysis models of flow cytometric DNA histograms of 1,301 breast cancer patients: results from the Multicenter Morphometric Mammary Carcinoma Project (MMMCP).

Conflicting prognostic results with regard to DNA flow cytometric cell cycle variables have been reported for breast cancer patients. An important reason for this may be related to differences in the interpretation of DNA histograms. Several computer programs based on different cell cycle fitting models are available resulting in significant variations in percent S-phase and other cell cycle variables. Our present study evaluated the prognostic value of percent S-phase cells obtained using 5 different cell cycle analysis models. Flow cytometric DNA histograms obtained from 1,301 fresh frozen breast cancer samples were interpreted with 5 different cell cycle analysis models using a commercially available computer program. Model 1 used the zero order S-phase calculation and "sliced nuclei" debris correction, model 2 added fixed G2/M- to G0/G1-phase ratio, and model 3 added correction for aggregates. Model 4 applied the first-order S-phase calculation and sliced debris correction. Model 5 fixed the coefficients of variation CVs of the G0/G1- and G2/M-phases in addition to applying the sliced nuclei debris correction and zero order S-phase calculation. The different models yielded clearly different prognostic results. The average percent S-phase cells of the aggregate correction model (model 3) provided the best prognostic value in all cases for overall survival (OS) as well as disease-free survival (DFS) (OS: p < 0.0001; DFS: p < 0.0001), in lymph node-positive cases (OS: p < 0.0001; DFS: p = 0.004) and in DNA-diploid subgroups (OS: p = 0.004; DFS: p = 0.001). For the lymph node negative and DNA-non-diploid subgroups, the percent S-phase of the second cell cycle reached slightly better prognostic significance than the average percent S-phase cells. In multivariate analysis, the average percent S-phase of the aggregate correction model had the best additional prognostic value to tumor size and lymph node status. In conclusion, different cell cycle analysis models yield clearly different prognostic results for invasive breast cancer patients. The most important prognostic percent S-phase variable was the average percent S-phase cells when aggregate correction was included in cell cycle analysis.

A simplified grading method of transitional cell carcinoma of the urinary bladder: reproducibility, clinical significance and comparison with other prognostic parameters.

OBJECTIVE: To determine the extent to which the biological potential of transitional cell neoplasms can be predicted by histological grading of the primary tumour in a two grade system using simple histological criteria and to evaluate the additional value of grading when combined with other prognostic factors. The inter-observer variability of the World Health Organization grading and the two grade system was tested. PATIENTS AND METHODS: The study included 311 patients with newly diagnosed transitional cell carcinoma of the urinary bladder. Two-hundred and fifty-six patients (82.3%) were men and 55 (17.7%) were women. Age ranged from 17 to 92 years with a mean of 66 years. The median follow-up was 38 months, with a maximum of 150 months (mean 46.2 months). RESULTS: A simplified grading system was developed in which only low-grade and high-grade tumours were distinguished. Reproducibility of this grading system was good to excellent with a group kappa value of 0.78. The survival of patients with low-grade tumours was significantly better than that of patients with high-grade tumours (P < 0.0001). The progression-free interval was also significantly longer in patients with low-grade tumours than in patients with high-grade tumours (P = 0.0032). Combining low-high grading, histological stage, mitotic index and age, histological stage appeared to be the most important parameter in predicting survival and progression. CONCLUSION: A reproducible and discriminating system such as this low-high grade system is an important prognostic factor when stage cannot be established with certainty.

Bladder cancer incidence and survival in the south-eastern part of The Netherlands, 1975-1989.

Trends in cancer occurrence and survival may reflect changing risks and prognosis, respectively, but may also be caused by changes in detection, classification and registration. Changed classification of low-stage papillary carcinomas may have a material effect on observed trends in the occurrence of bladder cancer. We studied the effect of the implementation of the WHO grading system and the third edition of the TNM staging system on bladder cancer incidence in the south-eastern part of the Netherlands. Data on superficial and invasive bladder cancer incidence between 1975 and 1989 were derived from the population-based Eindhoven cancer registry. Data on survival of patients with stages I-IV bladder cancer were derived from the municipal population registers. Age-adjusted bladder cancer incidence per 100,000 person-years rose from 25.9 to 40.7 in males and from 3.1 to 8.5 in females. This increasing trend was caused almost entirely by non-invasive pTa papillary carcinoma. A considerable shift was observed towards lower disease stages, which was less evident within the group of invasive tumours. The relative 5-year survival of patients with stages I-IV invasive bladder cancer was 59% in 1975-1977 and 70% in 1984-1986. After stratification by stage, however, no striking improvement was observed in the prognosis. We conclude that the increasing trend of bladder cancer occurrence in the Netherlands since 1975 has largely been caused by changed classification systems and reporting procedures for pTa tumours (formerly classified as papillomas).

Cytogenetic analysis in transitional cell carcinoma of the bladder.

The potential use of numerical chromosomal abnormalities as predictive factors for the clinical behaviour of transitional cell carcinoma (TCC) was investigated. The effects on survival and progression-free survival were measured in 91 patients with TCC treated by transurethral resection. The survival rate of patients having tumours with a diploid chromosomal modal number was significantly better than that of patients having tumours with a hyperdiploid chromosomal modal number. The survival rate of patients having TCC with diploid cells only was also significantly better than that of patients having TCC with both diploid and hyperdiploid cells. Progression-free survival was significantly higher in patients having TCC with a diploid modal number of chromosomes than in patients with a hyperdiploid modal number. Simultaneous evaluation of the modal chromosome number or chromosomal range, histological grade, category and mitotic index of the tumour, and the patient's age and sex as prognostic factors in multivariate analyses showed that the category of bladder carcinomas was the most important factor in predicting the survival rate. In patients with superficial tumours (category Ta and T1) the modal chromosome number was the most important factor in predicting survival. For progression-free survival, the modal chromosome number appeared to be the most important factor. It was concluded that the modal chromosome number in TCC was useful in predicting survival in patients with superficial tumours and in predicting progression-free survival in patients with tumours of all categories.

Image cytometric DNA analysis in transitional cell carcinoma of the bladder.

BACKGROUND: The current study was initiated to investigate measurable objective and reproducible characteristics that might have prognostic significance in bladder cancer. METHODS: Tumor samples from 91 patients with primary transitional cell carcinoma (TCC) of the urinary bladder were studied by DNA image cytometry and cytogenetic analysis. Image cytometry is a more sensitive method of determining ploidy than flow cytometry, especially in tumors with a low number of aneuploid cells. RESULTS: There was a significant difference in survival between DNA image cytometry-determined diploid and nondiploid cases. The presence of nuclei with a high DNA content indicated poor prognosis. The 2C deviation index (2CDI) also was an indicator of survival. Image cytometry-determined factors also were found to be strong predictors of progression-free survival. In multivariate analysis, 2CDI was the only cytometric parameter with an independent but weak correlation with survival. In multivariate analysis, none of the cytometric parameters had an important contribution to prediction of progression-free survival. In superficial tumors (Ta and T1), 2CDI appeared to be the most important independent predictor of survival. With respect to progression-free survival, tumors with a high mitotic index proved to have a worse prognosis. CONCLUSIONS: Parameters determined by DNA image cytometry appear to be valuable in predicting survival and progression-free survival and may be useful in addition to the classic parameters of stage and grade, especially in superficial TCC.

Prognostic significance of type IV collagen and laminin immunoreactivity in urothelial carcinomas of the bladder.

Invasion of a carcinoma involves the degradation and penetration of the subepithelial basement membrane (BM). This phenomenon might be used for histopathologic evaluation of neoplasms of the bladder. The authors studied the clinicopathologic data and tissue specimens of 125 cases of urothelial carcinomas collected prospectively. Penetration of the BM was evaluated by immunohistochemical staining of the BM components laminin and type IV collagen. The use of this parameter as a prognostic indicator in bladder cancer was assessed. The 5-year survival rate of patients having tumors with an interrupted or absent BM was significantly lower than that of patients having tumors with an intact BM. The rate of progression was greater in tumors with an interrupted or absent BM than in tumors with an intact BM. No association was found between BM status and recurrence. However, a significant correlation between tumor stage and BM staining was found. A correlation was also found between ploidy and BM staining as well as between histologic grade and BM staining pattern. When evaluating histologic grade, stage, ploidy, age, and BM score as prognostic parameters, the stage of bladder carcinomas turned out to be the most important factor in predicting the survival rate and the progression-free survival. However, BM staining was found to be of value for early identification of microinvasion and is helpful for correct staging of urothelial carcinomas.

Blood group isoantigen deletion and chromosomal abnormalities in bladder cancer.

The presence or absence of blood group isoantigens in 78 patients with transitional cell carcinoma of the bladder was correlated with tumor stage and grade, and results of chromosomal analysis. For blood group isoantigen detection the indirect immunoperoxidase method with monoclonal antibodies to A, B and H antigen was used. In 51 per cent of the 59 superficial tumors blood group isoantigens were demonstrable, whereas all deeper infiltrating and higher grade tumors were negative. However in superficial tumors the mode of blood group isoantigen expression did not correlate significantly with tumor recurrence and progression. A consistent correlation was demonstrated among chromosomal numbers, tumor grade and clinical course. The chromosomal abnormalities found and mode of blood group isoantigen expression, even in combination, had no prognostic value additional to the grading criteria used.

Grading in superficial bladder cancer. (1). Morphological criteria.

In a prospective study on the grading of superficial papillary neoplasms of the bladder a distinction was made between tumours showing only increased cellularity without appreciable cellular and nuclear deviation (grade 1), tumours showing slight cellular variation (grade 2a), and tumours showing clear cytological deviation and a tendency to lose normal polarity (grade 2b). Ninety-one patients with a superficial tumour were followed up for a mean of 24 months. Grade 2a tumours recurred later and in fewer patients than grade 2b tumours. Progression was seen in 4% of grade 2a tumours and in 33% of grade 2b carcinomas. Adapting our results to the WHO grading system, we suggest that all tumours in this study defined as grades 1 and 2a should be classified as low grade and tumours defined as grade 2b should be classified as intermediate grade.

Grading in superficial bladder cancer. (2). Cytogenetic classification.

Cytogenic analysis was performed in 92 newly diagnosed transitional cell bladder carcinomas and the results were correlated with the clinical course in superficial tumours. Low grade tumours appeared to have hypodiploid or peridiploid chromosomal numbers. Intermediate grade tumours were characterised by chromosomal counts up to the hyperdiploid range but could have a peridiploid modal number. In high grade tumours the modal number was hyperdiploid. The range in chromosomal counts appeared to be more reliable than the modal number as a predictor of the course of superficial tumours. The significant difference in chromosome numbers between low, intermediate and high grade tumours indicates that grading reflects major cytogenetic changes in the tumour cells.

Mesenteric lymphadenitis due to Yersinia enterocolitica.

The histopathological diagnosis of Yersinia enterocolitica infections in mesenteric lymph nodes is described on the basis of biopsy material from 14 cases collected at the Lymph Node Registry in Kiel. In all cases, the aetiological diagnosis was verified by demonstrating significant antibody titres in serological tests and, in two cases, by isolating Yersinia enterocolitica from faeces. The mesenteric lymph nodes showed a rather specific histological picture. In all cases, the capsule was thickened by oedema and stained metachromatically. The cortical and paracortical pulp was always hyperplastic owing to an increase in the number of immunoblasts, plasmablasts, and plasma cells. The sinuses were dilated and filled with intensely basophilic cells that varied in size from small to large (plasmacytoid cells and precursors). Small, or relatively large accumulations of "immature histiocytes" (transformed lymphocytes) were seen in the sinuses in about two thirds of the cases. Occasionally, there were small foci of small histiocytes (emigrated monocytes) in the cortical pulp. An abscess similar to the abscesses found in abscess-forming reticulocytic lymphadenitis due to Yersinia pseudotuberculosis was evident in only one case. The differential diagnosis is also discussed. The diseases to be considered are mesenteric lymphadenitis due to Yersinia pseudotuberculosis or salmonella infection, and nonspecific mesenteric lymphadenitis.