Squamous cell carcinoma of the penis: Predicting nodal metastases by histologic grade, pattern of invasion and clinical examination

With a diagnosis of squamous cell carcinoma of the penis, there is still a significant need to define the tumor criteria that allow the disease to be stratified according to the risk of developing lymph node metastases.The histopathology of the primary tumor in 72 consecutive patients with resected squamous cell carcinoma of the penis was reviewed for this study. Tumor tissue was reviewed for (1) histologic grade, (2) invasion pattern, (3) tumor stage, (4) proportion of poorly differentiated tumor cells, (5) invasion depth, (6) proportion of tumor necrosis, (7) angioinvasion, (8) histologic classification, (9) number of lesions, (10) growth pattern, (11) number of mitoses, (12) degree of keratinization, and (13) clinical groin status.It was found that the presence of inguinal lymph node metastases correlated in descending order of frequency with grade G2/G3, clinically positive groin status, reticular invasion, stage pT2/T3, >50% poorly differentiated tumor cells, depth of invasion, and comedolike tumor necrosis. These results revealed that the risk of inguinal lymph node metastasis in penile carcinoma can be predicted on the basis of 3 major factors: histologic grade, pattern of invasion, and clinical groin status.     

Histologic grade and perineural invasion are more important than tumor thickness as predictor of nodal metastasis in penile squamous cell carcinoma invading 5 to 10 mm

Penile squamous cell carcinomas (SCCs) invading to a depth inferior to 5 mm usually have very low risk for regional metastasis, whereas tumors thicker than 10 mm have a high metastatic potential. A significant number of squamous cell carcinomas, however, belong to an intermediate category (5 to 10 mm in thickness) in which the incidence of regional lymph node metastasis is very difficult to predict. Consequently, a frequent clinical dilemma is whether to perform or not inguinal dissection in this group of lesions. The objective of this study was to evaluate multiple risk factors for regional metastasis in tumors 5 to 10-mm thick. One hundred thirty-four partial penectomies with invasive carcinomas 5 to 10-mm thick, all of which with corresponding inguinal lymph node dissection, were evaluated. Factors evaluated were--patient's age, anatomic site, histologic grade, tumor thickness, anatomic levels of invasion, and vascular and perineural invasion. Grades were classified as 1, well; 2, moderately; and 3, poorly differentiated. To evaluate independent significance of various prognostic factors, a logistic regression analysis was performed, and a nomogram was prepared to evaluate metastatic risk according to histologic grade and perineural invasion. Groin metastasis was found in 66 of 134 patients (49%). High histologic grade and perineural invasion were statistically significant pathologic factors associated with groin metastasis. Nodal metastases were found in 2 of 25 grade 1 (8%), 24 of 46 grade 2 (52%), and 40 of 63 grade 3 carcinomas (63%) (P value 0.0001). Of 48 patients with perineural invasion, metastasis was found in 33 cases (69%) (P value 0.001). The average tumor thickness, anatomic level of invasion, and presence of vascular invasion were not statistically significantly different in metastasizing and nonmetastasizing neoplasms. Fifty percent of tumors invading 5 to 10 mm were not associated with metastasis and may be spared a nodal dissection. In this subset of patients, high histologic grade and perineural invasion were significant and useful risk factors associated with regional metastasis. The probability of inguinal node metastasis in patients with grade 1 tumors without perineural invasion is almost nonexistent whereas for high-grade tumors associated with perineural invasion is near 80%.     

Stage IA vulvar squamous cell carcinoma: an analysis of tumor invasive characteristics and risk

Early invasive vulvar squamous cell carcinoma (SCC) with less than 1.0 mm of invasion (FIGO stage IA) has been shown to have a minimal risk of lymph node metastasis and is associated with an excellent prognosis. The prognostic significance of other histologic parameters other than depth of invasion, however, remains controversial. Seventy-eight consecutive cases of vulvar SCC having a depth of invasion of 5.0 mm or less were reviewed and the clinical outcome compared with the type of surgical excision, the presence of concurrent lymph node metastases, the depth of tumor invasion, the tumor thickness, the tumor horizontal spread, the estimated tumor volume, tumor histologic subtype, tumor histologic grade, tumor pattern of invasion, tumor multifocality, presence of perineural invasion, presence of angiolymphatic invasion and the presence of precursor lesions, including the type of vulvar intraepithelial neoplasia and presence of lichen sclerosus. The only histologic feature for predicting concurrent lymph node metastasis was tumor depth of invasion. The 3 most important features of stage IA tumors in predicting tumor recurrence were the depth of invasion, presence of SCC at the surgical margins, and the histologic grade.     

Prognostic significance of vascular and perineural invasion in urothelial bladder cancer treated with radical cystectomy

PURPOSE: Data on the prognostic significance of tumor invading lymphatic and blood vessels in bladder cancer are controversial, while little is known about perineural invasion in this tumor. We determined the prognostic value of these parameters in radical cystectomy specimens. MATERIALS AND METHODS: Slides of 283 radical cystectomy specimens obtained from 1986 to 1997 were examined retrospectively with respect to tumor invasion in lymphatic and blood vessels, and perineural spaces. This review was performed while blinded to lymph node tumor involvement or the postoperative disease course. The Kaplan-Meier probability analysis of tumor-free survival and the log rank test were used to determine the prognostic effects of vascular and perineural invasion. Multivariate analysis using the Cox proportional hazards model was also performed. RESULTS: Lymphatic, blood vessel and perineural tumor invasion were present in 54.1%, 13.1% and 47.7% of specimens, respectively. Tumor progressed in 46.3% of patients. On univariate analysis all 3 factors showed strong prognostic significance. However, on multivariate analysis only blood vessel invasion, invasion depth and regional lymph node status were independent prognostic factors (p <0.05). CONCLUSIONS: Lymph node metastases, pT classification and blood vessel invasion are independent prognostic parameters of tumor-free survival that should be used to guide patient treatment after radical cystectomy. Invasion of the blood and lymphatic vessels should be commented on separately in the pathology report.     

Clinical significance of lymph node micrometastasis in gallbladder carcinoma

BACKGROUND: This retrospective study was intended to define the clinical significance of lymph node micrometastasis in gallbladder carcinoma. METHODS: A total of 1136 regional lymph nodes taken from 63 consecutive patients undergoing radical resection were examined histologically. Micrometastasis was defined as a metastasis missed on routine histologic examination with hematoxylin-and-eosin but detected by immunohistochemical examination with an antibody against cytokeratins 8 and 18. RESULTS: None of 9 patients (0%) with pT1 disease and 19 of 54 patients (35%) with pT2-4 disease had nodal micrometastases. Univariate analysis identified nodal micrometastasis, type of radical resection, M classification, pT classification, perineural invasion, pTNM stage, timing of radical resection, lymphatic vessel invasion, and pN classification as significant variables. Multivariate analysis revealed that nodal micrometastasis (P =.0003) and type of radical resection (P=.0044) were independent prognostic factors. Nodal micrometastasis affected survival adversely, despite the absence (P=.0002) or presence (P <.0001) of overt nodal metastasis. Nodal micrometastasis correlated significantly with invasive characteristics: lymphatic vessel invasion, perineural invasion, and distant metastasis. CONCLUSIONS: Lymph node micrometastasis is the strongest independent predictor of worse survival regardless of the overt nodal status and may indicate aggressive tumor biology among patients undergoing curative resection for gallbladder carcinoma.     

Extensive retraction artifact correlates with lymphatic invasion and nodal metastasis and predicts poor outcome in early stage breast carcinoma

Retraction artifact resulting in clear spaces around tumor cell nests is frequently seen in histologic material and may present difficulty in their differentiation from lymphovascular invasion. We noticed that retraction artifact seemed to be more common around groups of breast cancer cells compared with benign acini, and when extensively present, metastasis to axillary lymph nodes was often seen. Thus, we performed a study of 304 cases of stage pT1 and pT2 breast carcinomas to test our hypothesis that extensive retraction artifact in tumors correlates with lymphatic spread and outcome. Tumors were evaluated to determine the presence and extent of retraction artifact around tumor cell nests and the presence of lymphatic invasion. Lymphatic invasion was confirmed by D2-40 immunostaining. The extent of retraction artifact in tumors was correlated with clinicopathologic tumor features and patient outcome. Variable degree of retraction artifact was present in 183 of 304 (60%) invasive carcinomas, with its extent ranging from 0% to 90% (median 5%). The extent of retraction artifact showed a significant correlation with tumor size, histologic type, histologic grade, presence of lymphovascular invasion, and nodal metastasis. Further, extensive retraction artifact was significantly associated with poor overall and disease-free survival in both univariate and multivariate analyses. We propose that the apparent retraction of the stroma from cells of invasive breast carcinoma on routine histologic sections is not a phenomenon merely due to inadequate fixation as currently believed. Rather, it likely signifies important biologic changes that alter tumor-stromal interactions and contribute to lymphatic spread and tumor progression.     

Lymph-node metastases in intermediate-risk squamous cell carcinoma of the penis

OBJECTIVE

To evaluate the metastatic risk of pT1 G2 squamous cell carcinoma (SCC) of the penis.

PATIENTS AND METHODS

We retrospectively reviewed 20 patients with pT1 G2 penile SCC and determined their groin status at first presentation, their nodal status after inguinal lymph node dissection and their follow‐up for at least 18 months.

RESULTS

Four of the 20 patients had a clinically positive groin; three of these were found to have lymph node metastases. Among the 16 patients with a clinically negative groin, one of five who had surgical lymph node staging had lymph node metastases. During surveillance six of 11 patients developed lymph node metastases. There was lymphovascular invasion in three of 10 patients with lymph node metastases.

CONCLUSIONS

As the metastatic risk of pT1 G2 penile SCC was 50% in this series of patients, and 44% in those with an initially negative groin, surgical staging of inguinal lymph nodes is recommended in patients with pT1 G2 penile SCC.     

Evaluation of Clinical and Histomorphological Parameters as Potential Predictors of Occult Metastases in Sentinel Lymph Nodes of Early Squamous Cell Carcinoma of the Oral Cavity

Background

Sentinel node biopsy (SNB) for cN0 early squamous cell carcinoma (SCC) of the oral cavity has been validated by numerous studies. Around 30% of SNB will detect occult disease. Several clinical and morphological features of the primary tumor have been claimed to be predictive for occult metastasis in elective neck dissections. The aim of this study was to assess these factors in the context of SNB.

Methods

Seventy-eight patients undergoing SNB for T_1/2 oral SCC from the years 2000 to 2007 were prospectively included. Primary tumors were reviewed for the following morphological and clinical parameters: grade of differentiation, tumor depth, tumor thickness, perineural invasion, lymphatic invasion, vascular invasion, muscle invasion, lymphoplasmacytic infiltration, and mode of invasion, age, gender, primary tumor site, tumor side, and cT category.

Results

Statistical analysis revealed significance to predict occult metastasis in the SNB for grade of differentiation (P = 0.002), lymphatic invasion (P < 0.001), and mode of invasion (P < 0.001). None of the other factors reached significance. The mean tumor depth was 6.45 mm (range 0.72–15.15 mm) and the mean tumor thickness was 7.2 mm (range 0.72–15.15 mm). None of the cutoff values reached significance for predicting occult disease.

Conclusions

Tumor depth and tumor thickness failed to achieve statistical significance for prediction of occult metastases in the context of SNB. Patients with cN0 early squamous cell carcinoma of the oral cavity should be offered SNB regardless of their tumor depth and thickness. Poorly differentiated carcinomas, carcinomas with lymphangiosis, and carcinomas with a dissolute mode of invasion show a high probability of positive SNB.     

Renal sinus involvement in renal cell carcinomas

The renal sinus is the fatty compartment located within the confines of the kidney not delineated from the renal cortex by a fibrous capsule. Because it contains numerous veins and lymphatics, invasion into this compartment may permit dissemination of a tumor otherwise regarded as renal-limited. Thirty-one consecutive renal carcinomas were studied: 22 clear cell renal cell carcinomas (3 multilocular cystic renal cell carcinomas), 4 chromophobe renal carcinomas, and 5 papillary renal carcinomas. The entire interface between the neoplasm and the sinus was embedded. Seventeen carcinomas did not invade the renal sinus and 16 were pT1 or pT2 tumors. Fourteen carcinomas, 13 clear cell renal cell carcinoma and one chromophobe renal carcinoma, invaded the renal sinus fat, and 9 of 14 invaded the lumen of renal sinus veins (all clear cell renal carcinomas). Although 14 of 22 clear cell renal carcinomas appeared to be renal limited pT1 and pT2 cancers, 6 of 14 carcinomas invaded sinus fat and 4 invaded into the lumen of renal sinus veins. Compared with the nine sinus-negative clear cell renal cell carcinomas, the 13 sinus-positive cancers were larger, exhibited more frequent renal capsule and renal vein involvement, and had higher nuclear grades. Renal sinus invasion was most common in clear cell renal cell carcinomas but was uncommon (one in 12) in 3 more indolent renal cell carcinomas: multilocular cystic renal cell carcinoma, chromophobe renal carcinoma, and papillary renal carcinoma. The follow-up period was short (1-17 months), but metastases developed in four of 31 cases. In three cases with metastases, carcinoma had involved the lumen of sinus veins but not the main renal vein, although two of three had also invaded through the renal capsule. This study shows that in carcinomas which appear to be renal limited (pT1/pT2), seven of 23 (30.4%) had invaded sinus fat and four of 23 (17.4%) had invaded sinus veins. We conclude that renal sinus invasion, especially sinus vein invasion, could identify a patient at risk for metastases even in a putative renal limited tumor, and suggest that all cases be examined for this feature. Renal sinus invasion merits further investigation to establish its prognostic importance and possible incorporation into future revisions of the TNM staging system for renal cell carcinomas.     

Tumor stage, vascular invasion and the percentage of poorly differentiated cancer: independent prognosticators for inguinal lymph node metastasis in penile squamous cancer

PURPOSE: We determine if histopathological factors of the primary penile tumor can stratify the risk of the development of inguinal lymph node metastases. MATERIALS AND METHODS: Clinical records of 48 consecutive patients with squamous cell carcinoma of the penis who underwent resection of the primary lesion and either inguinal lymph node dissection or were observed for signs of recurrence (median followup 59 months) were reviewed. Parameters examined included pathological tumor stage, quantified depth of invasion and tumor thickness, histological and nuclear grade, percentage of poorly differentiated cancer in the primary tumor, number of mitoses and presence or absence of vascular invasion. Variables were compared in 18 lymph node positive and 30 lymph node negative cases. RESULTS: Pathological tumor stage, vascular invasion and presence of greater than 50% poorly differentiated cancer were the strongest predictors of nodal metastasis on univariate and multivariate regression analyses. None of 15 pT1 tumors exhibited vascular invasion or lymph node metastases. Of 33 patients with pT2 or greater tumors 21 (64%) had vascular invasion and 18 (55%) had metastases. Only 4 of 25 patients (15%) with 50% or less poorly differentiated cancer in the penile tumor had metastases compared with 14 of 23 patients (61%) with greater than 50% poorly differentiated cancer (p = 0.001). No other variables tested were significantly different among the patient cohorts. CONCLUSIONS: Pathological stage of the penile tumor, vascular invasion and greater than 50% poorly differentiated cancer were independent prognostic factors for inguinal lymph node metastasis. Prophylactic lymphadenectomy in compliant patients with pT1 lesions without vascular invasion and 50% or less poorly differentiated cancer does not appear warranted.     

Correlation of size and focality with prognosis in small breast carcinoma: a single institution case series

Aim of the studyThe clinical behavior and prognosis of small multifocal and microinvasive breast cancers are still debated together with the best method of assessing tumor size in multiple invasive carcinomas. This study evaluates the clinico-pathological features of single and multiple breast cancers up to 0.5 cm in order to evaluate the rate of recurrences.Materials and methodsWe retrospectively analyzed 170 node-negative patients consecutively treated at European Institute of Oncology from 2001 to 2006. We divided them into Group I (pT1mi) and Group II (pT1a) furtherly divided in subgroups, according to focality and aggregate diameter. For each group we assessed tumor size, (multi)focality, extensive in situ component (EIC), histology, grade, peritumoral vascular invasion (PVI), hormonal receptor status (HR), HER-2 expression, Ki67 expression.ResultsWe observed that the frequency of local recurrences and distant metastases in group I was higher among those with a single focus; whereas in group II, it was higher in multifocal carcinomas. Then, by comparing the two groups, the prognosis was better in multiple pT1mi than in similarly sized unifocal pT1a.ConclusionsMicroinvasive carcinomas are associated with a good prognosis, even if they seem to have a more aggressive intrinsic biological behavior. Multifocality seems to be correlated with a worse prognosis in case of invasive carcinomas pT1a. In case of microinvasive carcinomas, by contrast, multifocality per se does not seem to affect the recurrence rate.     

Prediction of lymph node status by analysis of prognostic factors and possible indications for elective axillary dissection in T1 breast cancers.

OBJECTIVE: To identify those patients with T1 breast cancers with lower risk of nodal metastases who can safely be spared axillary dissection. DESIGN: Retrospective study. SETTING: University hospital, Italy. SUBJECTS: Review of clinical records and histopathological slides of 547 patients with T1 breast cancer, operated on between 1984 and 1997. MAIN OUTCOME MEASURES: Incidence of axillary metastases in relation to age, menopausal status, diameter and grade of tumour, vascular invasion, DNA ploidy, S-phase fraction and hormone receptor state, by univariate and multivariate analysis. RESULTS: Axillary metastases were present in 159 patients (29%). On univariate analysis, diameter of tumour 10 mm or less (pT1a/pT1b cancers), no vascular invasion, and grade 1 tumour were significantly correlated with a lower risk of nodal metastases, but only vascular invasion (p = 0.0001, odds ratio = 3.1) and diameter of tumour (p = 0.04, odds ratio = 1.6) were independent predictors on multivariate analysis. Among 34 pT1a/pT1b cancers, with low grade of tumour and no vascular invasion, only 2 (6%) had axillary metastases. When only one favourable predictive factor was associated with diameter of tumour of 10 mm or less, the incidence of axillary metastases ranged from 12% for 43 patients with grade 1 cancers to 13% for 76 patients with no vascular invasion. CONCLUSIONS: Axillary dissection may be avoided in pT1a and pT1b breast cancers (< or = 10 mm), with low grade of tumour or no vascular invasion. T1 breast cancers 10 mm or less in diameter should be treated by a two-step approach, first wide excision of the tumour and then axillary dissection or not depending on pathological examination of the primary tumour.     

Survival analysis for localized renal cell carcinoma. Prognostic value of 1997 TNM classification

Backgroundthe 5th edition of TNM classification for renal cell carcinoma changed the cut-off point of the tumor size for localized tumors, achieving a better distribution of patients with similar survival. Nevertheless, because of the variable evolution of renal cell carcinoma, the prognostic significance of tumor size is questioned as a staging criterion in organ-confined renal cell carinoma. We analyse renal cell carcinoma specific survival and the prognostic significance of tumor size in I and II stage.MethodsWe made a retrospective study with 158 renal cell carcinoma surgically treated in our hospital along 12 years. It was created a data base with clinical variables from patient and tumor and analyzed pathological staging, nuclear grade and specific survival, overall stage I and II.Results27 renal cell carcinoma were pT1 (17.08%), 52 pT2 (32.91%), 45 pT3A (28.45%), 10 pT3B (6.32%), y 24 pT4 (15.18%). The specific survival at 5 years for pT1-pT2, I-II stage, was 100% and 94% respectively, and no statistic significant differences were found between stage I and II (log-rank test 0.53, p>0.05). The specific survival at 5 years for pT3A, pT3B, y pT4 was 76.5%, 66.6% y 38.4%. There was a significant difference in survival in accordance with the tumor location, intrarenal (T1 y T2) versus extrarenal (T3A, T3B, T4) (log-rank test 9.06, p < 0.05). According to nuclear grade we don’t find significant differences for pT1 y pT2 (Fisher test, p=1). Regarding the relation between pT stage and nuclear grade of the tumor we obtained a ?2 inear tendency of 38.19, p < 0.001.ConclusionThe differences in the evolution of the organ-confined renal cell carcinoma with respect to the tumor size may be due to other molecular and biological variables, probably associated with stage. not controlled in essays. The TNM classification for organ-confined renal cell carcinoma based in tumor size seems artificial. New revisions of the classification system are necessary to identify which organ-confined carcinoma will have unfavourable evolution and to include them in a different category.     

Clinicopathologic Differences between Long-Term and Short-Term Postoperative Survivors with Advanced Gallbladder Carcinoma

p < 0.05), hepatic infiltration < 5 mm ( p < 0.01), histologic grade of papillary or well differentiated adenocarcinoma ( p < 0.01), absent or minimal venous, lymphatic, and perineural invasion ( p < 0.01), and lymph node metastasis limited to the hepatoduodenal ligament ( p < 0.05). It was concluded that the patients with subserosal invasion have a hope for long-term survival by extended cholecystectomy or more aggressive surgery when hepatic infiltration and venous, lymphatic, and perineural invasion are absent or minimal, the histologic grade is papillary or well differentiated adenocarcinoma, and lymph node metastasis is limited to the hepatoduodenal ligament.     

Prognostic impact of tumor size on pT2 renal cell carcinoma: an international multicenter experience

PURPOSE: The current tumor classification for renal cell carcinoma classifies pT2 tumors as larger than 7 cm in greatest dimension and limited to the kidney. We examined the current pT2 tumor classification of renal cell carcinoma and determined whether a tumor size cutoff exists that would improve prognostic accuracy. MATERIALS AND METHODS: We studied 706 patients with pT2 renal cell carcinoma treated with surgical extirpation at 9 international academic centers. Data collected from each patient included age at diagnosis, gender, 2002 TNM (tumor, node, metastasis) stage, tumor size, nuclear grade, performance status, histological subtype and disease specific survival. Disease specific survival was evaluated with univariate and multivariate analysis. RESULTS: Median followup was 52 months. Univariate Cox regression analysis showed a significant association of tumor size with disease specific survival (HR 1.11, p<0.001). An ideal tumor size cutoff of 11 cm was identified, which led to the stratification of 2 groups with respect to disease specific survival (p<0.0001) with 5 and 10-year survival rates of 73% and 65% for pT2 11 cm or less, and 57% and 49% for pT2 larger than 11 cm, respectively. The incidence of metastases was significantly greater in the larger than 11 cm group, while Eastern Cooperative Oncology Group performance status, Fuhrman grade and histological subtype were similar. Multivariate Cox regression analysis retained tumor size as an independent prognostic factor and as the strongest prognostic factor for patients with pT2N0M0 disease. CONCLUSIONS: Our data suggest that the current pT2 classification can be improved by subclassification into pT2a and pT2b based on a tumor size cutoff of 11 cm. Patients in the proposed pT2bN0M0 group are at higher risk for death from renal cell carcinoma and should be considered for adjuvant therapies. External validation is warranted before suggesting change to the TNM classification.     

Patterns of metastasis in muscle-invasive bladder cancer (pT2-4): An autopsy study on 367 patients.

Background: Metastatic status is an essential determinant of prognosis of patients with muscle-invasive bladder cancer treated by cystectomy, and preoperative metastases detection is crucial for treatment selection in these patients. To better understand the metastatic behavior of bladder tumors, autopsies of patients with muscle-invasive bladder carcinomas (pT2-4) were evaluated. Methods: Protocols and histologic sections from autopsies of 367 patients with pT2-4 bladder cancer were reviewed. Results: Metastases were found in 251 of 367 patients (68%). The most frequent sites of metastases were regional lymph nodes (90%), liver (47%), lung (45%), bone (32%), peritoneum (19%), pleura (16%), kidney (14%), adrenal gland (14%), and the intestine (13%). There was no difference in the frequency and location of metastases between 308 transitional cell carcinomas and 38 squamous cell carcinomas. The frequency of metastases increased with local tumor extension (patients with cystectomy: pT2, 36%; pT3a, 45%; pT3b, 69%; pT4, 79%; p < 0.0001). For all pT classifications, the frequency of metastases was slightly higher in patients treated by cystectomy (metastases in 45% of 29 pT2 and 89% of 28 pT4 tumors) than in patients without cystectomy (36% of pT2 and 79% of pT4 tumors). Conclusions: These results argue against relevant clinical differences between histologic tumor types. The high frequency of metastases in patients having undergone cystectomy indicates that metastasis often occurs before the time of diagnosis. This emphasizes the need for a better prediction of the metastatic capability of these tumors at the time of diagnosis.     

p53 overexpression correlates with increased survival in patients with squamous carcinoma of the tongue base.

Epidermal growth factor receptor (EGFR), transforming growth factor alpha (TGFA), and p53 are frequently overexpressed in squamous cell carcinomas (SCC) of the upper aerodigestive tract. We chose to study SCC of the tongue base, which is often advanced at presentation and fatal, to evaluate whether overexpression correlates with survival. Complete follow-up was available for 20 patients, 18 of whom had stage III or IV disease. A number of clinical (age, sex, stage of disease) and histologic (tumor grade, keratinization, mitotic rate, perineural invasion, lymphatic invasion, vascular invasion, host response) variables were analyzed. None of these variables correlated with survival. Immunohistochemical analysis was performed on paraffin-embedded tissue from each patient. Because EGFR and TGFA expression were routinely found in normal squamous epithelium, overexpression was considered present if greater uptake of the antibody was manifested by a deeper immunostain. In contrast, p53 oncoprotein was not detected in normal epithelium, so detection of the antibody was believed to indicate overexpression. EGFR was overexpressed in 60% of tumors, TGFA in 35%, and p53 in 20%. Those patients who had an overexpression of p53 had a greater mean survival than those who did not (48 versus 16 months, respectively, p = 0.06). This difference was significant for patients with clinical stage IV lesions (p = 0.03). EGFR overexpression and TGFA overexpression did not correlate with survival. p53 may serve as a biologic marker indicative of improved survival potential.     

Pathology and biology of pancreatic ductal adenocarcinoma

Introduction: Ductal adenocarcinoma of the pancreas is a highly aggressive tumor with early local spread beyond the pancreas, predominantly to the retroperitoneum, but also with invasion of adjacent great vessels and adjacent organs. Discussion: Anterior extension may lead to perforation of the visceral peritoneum and spread within the peritoneal cavity. Cytology in peritoneal lavage can be positive before any peritoneal metastasis is seen. Invasion of lymphatics and veins as well as perineural invasion are common. The lymph drainage of the pancreas is multidirectional to superior, inferior, anterior, posterior and left lymph nodes. In node-negative cases, isolated tumor cells in the sinus of regional lymph nodes may be found by immunocytochemistry; such findings must be distinguished from micrometastasis. The same applies to isolated tumor cells in bone marrow. Prognosis: The independent prognostic significance of isolated tumor cells in the regional lymph nodes and in the bone marrow remains to be proven. For classification of anatomic extent the new, fifth edition (1997) of the UICC TNM classification should be used. The complex Japanese classification cannot be directly compared with the UICC system. Conclusion: Tumor size and histologic grade influence the extent of spread. Anatomic extent and histologic grade are the strongest predictors of outcome. Received: 13 February 1998