Miklós Tarján

Nodal staging of colorectal carcinomas from quantitative and qualitative aspects. Can lymphatic mapping help staging

Retrospective data analysis was performed to determine the minimum number of lymph nodes required for the staging of colorectal carcinomas, and a prospective feasibility study was carried out to identify sentinel nodes in order to clarify whether these may predict the nodal status. From among 240 colorectal carcinoma specimens investigated between 1996 and 1998, 224 tumors were analyzed for their nodal status. Lymphatic mapping with vital patent blue dye injection into the peritumoral subserosal layer was performed in 25 patients. Blue nodes were identified by the pathologist in the unfixed specimen immediately after the resection of the bowel and were assessed separately. Of the 123 node-positive carcinomas, 40 had more than 3 nodes involved. The nodal positivity increased substantially when more than 6 nodes were assessed. The cumulative percentage analysis demonstrated that ideally 16 and 13 nodes should be obtained for the identification of any nodal involvement or the involvement of more than 3 nodes, respectively. Lymphatic mapping was successful in 24 patients (96%). Blue nodes were predictive of the nodal status in 19 cases (79%), and were the only sites of metastasis in 2 patients (15% of the node-positive cases). Lymphatic mapping with the vital blue dye technique does not seem to facilitate the staging of colorectal cancers, at least in our patient population with relatively large and deeply infiltrating tumors, and unless the technique is improved or other selective features of lymph nodes are found, all lymph nodes should be assessed. A minimum of 6 nodes, and an optimum of 16 nodes or more, are suggested from these series.

Breast cancer multifocality, disease extent, and survival

The prognostic information implied in subgross morphologic parameters such as lesion distribution (unifocal, multifocal, or diffuse) and disease extent in breast cancer has remained largely unexplored in the literature. We aimed to test whether these parameters influence survival in breast carcinoma. The parameters were assessed in a series of 574 cases, all documented in large-format histology sections. We used Cox proportional hazards regression accompanied by Kaplan-Meyer survival curves, with P < .05 regarded as significant. The invasive component was unifocal in 62% (311/499), multifocal in 24% (122/499), and diffuse in 5% (26/499) of the cases. Combining the in situ and invasive tumor components resulted in 48% (274/574) unifocal, 25% (141/574) multifocal, and 20% (117/574) diffuse tumors. Sixty percent (347/574) of the tumors were categorized as having limited extent (occupying an area <40 mm in largest dimension) and 29% (164/574) as extensive. Highly significant (P < .0001) differences were observed in 10-year disease-specific cumulative survival among the cases with unifocal, multifocal, and diffuse invasive (89.6%, 76.0%, and 63.6%, respectively) and combined (92.3%, 82.3%, and 75.7%, respectively) lesion distribution. Patients with extensive tumors exhibited a significantly lower cumulative survival (P < .0001) compared with those with limited extent (91.6% and 75.5%) and a statistically significantly 1.89-fold (95% confidence interval, 1.07-3.37; P = .03) risk for breast cancer death after controlling for tumor attributes, type of surgery, and adjuvant therapy. The hazard ratio for breast cancer death for mutifocal and/or diffuse tumors versus unifocal ones was 1.96 (95%; 1.11-3.48; P = .02) after controlling for the same factors. Lesion distribution and disease extent represent important independent survival-related prognostic parameters in breast carcinoma.

The distribution of lesions in 1–14-mm invasive breast carcinomas and its relation to metastatic potential

We analyzed 301 consecutive cases of 1–14-mm invasive breast carcinomas documented in large-format histological sections to determine the distribution of invasive and in situ foci. We also aimed to determine whether this distribution was related to the frequency of demonstrable vascular invasion and lymph node metastases. One third of the carcinomas (31.9%, 96 cases) had a multifocal invasive component and a more than doubled relative risk of vascular invasion (RR = 2.3642, 95% confidence interval (CI) = 1.5077–3.7073) and lymph node metastasis (RR = 2.7760, 95% CI = 1.6337–4.7171) compared to unifocal invasive carcinomas. Invasive carcinomas with diffuse in situ component had an elevated relative risk for vascular invasion (RR = 2.2201, 95% CI = 1.4049–3.5083) and lymph node metastasis (RR = 1.9201, 95% CI = 1.1278–3.2691) compared to those with unifocal or multifocal in situ lesions. However, multifocality of the invasive component was associated with a substantially elevated risk of vascular invasion and lymph node metastasis, even in cases with diffuse in situ component. Similar observations were made in the 1–9- and 10–14-mm invasive carcinoma subgroups. These findings indicate that lesion distribution has prognostic relevance for 1–14-mm invasive breast carcinomas and underline the importance of using special techniques in breast pathology for proper assessment of this parameter.

Multifocal breast cancer documented in large-format histology sections: Long-term follow-up results by molecular phenotypes

The prognostic significance of molecular phenotype in breast cancer is well established in the literature. Recent studies have demonstrated that subgross lesion distribution (unifocal, multifocal, and diffuse) and disease extent also carry prognostic significance in this disease. However, the correlation of molecular phenotypes with subgross parameters has not yet been investigated in detail.

Expression of LRIG1 is associated with good prognosis and human papillomavirus status in oropharyngeal cancer

Background:The incidence of human papillomavirus (HPV)-associated oropharyngeal cancer has increased rapidly during the past decades. HPV is typically associated with a favourable outcome; however, a need exists for new and more effective prognostic and predictive markers for this disease. Leucine-rich repeats and immunoglobulin-like domains (LRIG)-1 is a tumour suppressor protein that belongs to the LRIG family. LRIG1 expression has prognostic significance in various human cancers, including cervical cancer, where HPV is a key aetiological agent.Methods:The prognostic value of LRIG1 and LRIG2 immunoreactivity was investigated in tumour specimens from a Swedish cohort of patients with tonsillar and base of tongue oropharyngeal cancers, including 278 patients.Results:LRIG1 immunoreactivity correlated with disease-free survival and overall survival in univariate and multivariate analyses. Notably, patients with HPV-positive tumours with high LRIG1 staining intensity or a high percentage of LRIG1-positive cells showed a very good prognosis. Furthermore, LRIG1 expression correlated with HPV status, whereas LRIG2 expression inversely correlated with HPV status.Conclusions:Taken together, the results suggest that LRIG1 immunoreactivity could be a clinically important prognostic marker in HPV-associated oropharyngeal cancer.

Malignant fibrous histiocytoma of the kidney

Malignant fibrous histiocytoma (MFH) is extremely rare in the kidney. We present a case of primary renal MFH in a 55-yearold male and briefly review the disease. It is essential to differentiate MFH from more frequent renal cell carcinomas, because MFH represents a worse prognosis and requires different treatment.Malignant fibrous histiocytoma (MFH) is extremely rare in the kidney. We present a case of primary renal MFH in a 55-year-old male and briefly review the disease. It is essential to differentiate MFH from more frequent renal cell carcinomas, because MFH represents a worse prognosis and requires different treatment.

Distance of lymph nodes from the tumor: An important feature in colorectal cancer specimens

CONTEXT The nodal stage of colorectal cancers is prognostically important. Most current staging guidelines concentrate on the minimum number of evaluated lymph nodes required for an adequate node-negative stage. OBJECTIVE To evaluate the distance of the lymph nodes from the primary tumors as a possible qualitative feature that could help pathologists select between these nodes. DESIGN Prospective analysis of 100 colorectal carcinoma specimens. SETTING Department of Pathology of a medium-sized teaching hospital. PATIENTS Consecutive patients with colorectal cancer. INTERVENTIONS Nodes abluminal from the tumor and the adjacent bowel segments were recovered in 4 fractions (A through D) in 100 colorectal carcinoma specimens. MAIN OUTCOME MEASURES Distribution of metastatic nodes in fractions A through D, and their influence on nodal stage. RESULTS All tumors but 1 were classified correctly as node-negative or node-positive on the basis of fraction A (nodes abluminal from the tumor and from the 1-cm-long segments proximal and distal to the tumor). All tumors but 1 were appropriately classified as pN0, pN1, or pN2 on the basis of fractions A and B (nodes abluminal from the tumor and from the 3-cm-long segments proximal and distal to the tumor). CONCLUSIONS Lymph nodes should be recovered from fractions A and B, and if 3 nodes are reported positive, additional nodes should be sought to determine the extent of nodal involvement. This qualitative restriction of the grossing protocol may reduce the time spent in recovering nodes from colorectal carcinoma resection specimens.

Molecular phenotype of the foci in multifocal invasive breast carcinomas: Intertumoral heterogeneity is related to shorter survival and may influence the choice of therapy

Multiple synchronous, ipsilateral, invasive foci of breast carcinomas are frequent and are associated with a poorer prognosis. Few studies have investigated the prognostic and therapeutic implications of heterogeneity of such foci.

Primary adenocarcinoma of the seminal vesicle.

Primary adenocarcinomas of the seminal vesicle (SVC) are very rare and poorly understood neoplasms with only somewhat more than 50 histologically confirmed cases reported in the literature. We demonstrate a case of SVC and discuss the problems related to diagnosis in this tumor.

Sarcomatoid renal cell carcinoma with foci of chromophobe carcinoma

Both chromophobe carcinoma and sarcomatoid carcinoma of the kidney are rare. The former is characterized by a relatively good prognosis, while the latter is a highly aggressive tumor. Coexistence of the two components in one renal tumor, which has been reported only rarely, is therefore paradoxical. Both sarcomatoid and chromophobe renal carcinoma were diagnosed in a 52-year-old woman following nephrectomy and resection of metastases in the right lobe of the liver. She died of the disease two months after the first operation; only the sarcomatoid component of her tumor was seen in the liver metastasis and the recurrent carcinoma. Differences in phenotype, immunophenotype and DNA-ploidy patterns of the two components are reported. The intensive p53 staining observed only in the sarcomatoid area supports the role of the TP53 gene in the transformation of chromophobe renal carcinoma to sarcomatoid carcinoma.