Concordance of histopathologic and cytologic grading in musculoskeletal sarcomas: can grades obtained from analysis of the fine-needle aspirates serve as the basis for therapeutic decisions?

BACKGROUND: Utilization of fine-needle aspiration (FNA) for the diagnosis of musculoskeletal lesions has been de-emphasized by many clinicians because of concerns regarding the technique's ability to supply all information necessary for prognostication and appropriate selection of therapy. Paramount among the concerns is the belief that FNA is incapable of supplying precise subtyping and grading in many cases. Secondary concerns regarding the use of FNA involve its perceived inability to supply adequate tissue for ancillary studies including immunohistochemistry and molecular diagnostic analysis. The authors investigated the ability of FNA to accurately subtype and grade a series of 107 primary sarcomas of the musculoskeletal system. METHODS: The files of the Departments of Pathology at Duke University Medical Center and the University of California at Los Angeles and the private consultation files of one of the authors were searched for all fine-needle aspirates of sarcomas arising within the musculoskeletal system. A total of 107 cases were obtained and reviewed by three board-certified cytopathologists. Each cytopathologist independently assigned subtype when possible and generated a grade for each of the sarcomas. Corresponding surgical material was available for 77 cases. The surgical material was re-reviewed for accuracy of diagnosis and assignment of grade independently of the cytologic examination. Correlation of cytologic grade with histopathologic grade was made and analyzed by the kappa test. In addition, agreement on grade between cytopathologists was analyzed, and accuracy of histologic subtype prediction by cytologic analysis was studied. RESULTS: Most of the sarcomas were cytologically graded as Grade 1 or 2 but were assigned a histologic grade of 2 or 3. Cytopathologist A graded 93% of the sarcomas as either Grade 1 or 2, cytopathologist B graded 89% of cases as Grade 1 or 2, and cytopathologist C graded 94% of cases as Grade 1 or 2. Histologic evaluation demonstrated 82% of cases to be Grade 2 or 3. Correlation of cytologic and surgical grade varied among the observers. Cytopathologist A showed the highest degree of correlation between cytologic and surgical grade with an r value of 0.5. The corresponding r values for cytopathologists B and C were 0.46 and 0.41, respectively. Correlation between cytologic and surgical grade was significant for all three observers (P < 0.001). Only nuclear grade showed a consistent correlation in predicting final surgical pathology grade. Cellularity, mitotic rate, and the presence of necrosis were not statistically significant for predicting histopathologic grade. Accurate exact subtyping by cytologic examination was achieved in approximately 55% of cases. Prediction of histopathologic subtype by cytologic analysis was most successful when a distinctive stroma was present or high-grade features indicative of malignant fibrous histiocytoma were observed. There was little agreement as to histopathologic type as predicated by cytology for low-grade spindle cell sarcomas. CONCLUSIONS: Although there was a statistically significant correlation between cytologically assigned grade and final histopathologic grade, statistical analysis revealed only a moderate correlation between the two with an overall r value of approximately 0.57. Cytologic analysis tended to undergrade in comparison to final histopathologic grading. Only analysis of nuclear atypia showed good correlation with final surgical grade. Fine-needle aspiration was only moderately successful at predicting histopathologic subtype for musculoskeletal sarcomas in this series.     

Application of volumetric modulated arc therapy (VMAT) in a dual-vendor environment

Background

To investigate whether expression of carbonic anhydrase XII (CA12) is associated with histologic grade of the tumors and radiotherapy outcomes of the patients with invasive cervical cancer.

Methods

CA12 expression was examined by immunohistochemical stains in cervical cancer tissues from 183 radiotherapy patients. Histological grading was classified as well (WD), moderately (MD) or poorly differentiated (PD). Oligonucleotide microarray experiment was performed using seven cervical cancer samples to examine differentially expressed genes between WD and PD cervical cancers. The association between CA12 and histological grade was analyzed by chi-square test. CA12 and histological grades were analyzed individually and as combined CA12 and histologic grade categories for effects on survival outcome.

Results

Immunohistochemical expression of CA12 was highly associated with the histologic grade of cervical cancer. Lack of CA12 expression was associated with PD histology, with an odds ratio of 3.9 (P = 0.01). Microarray analysis showed a fourfold reduction in CA12 gene expression in PD tumors. CA12 expression was marginally associated with superior disease-free survival. Application of the new combined categories resulted in further discrimination of the prognosis of patients with moderate and poorly differentiated tumor grade.

Conclusions

Our study indicates that CA12 may be used as a novel prognostic marker in combination with histologic grade of the tumors.     

Cell features and patterns in fine-needle aspirates of hepatocellular carcinoma

The values of the cytologic features of individual cells and cellular patterns in aspirated materials in the diagnosis of 49 hepatocellular carcinomas (HCC) were investigated. Excellent cytologic specimens were obtained by percutaneous aspiration biopsy with a heparinized fine 22-gauge needle. In the well-differentiated type of HCC, a correct diagnosis of malignancy was difficult from the cytologic features of individual cells because of their resemblance to normal hepatocytes. In contrast, in moderately differentiated and poorly differentiated types of HCC, a correct diagnosis of malignancy was easily made from the features of individual cells, but there was little or no cytologic evidence of the hepatic origin of the cells. Comparison of histologic and cytologic findings in aspirated materials obtained from the same patients showed that the cellular patterns seen in cytologic specimens faithfully reflected the histologic structures of HCC. Various characteristic cellular patterns were recognized only in specimens obtained from patients with HCC, but not in those from patients with benign liver diseases. These cellular patterns were very useful not only for diagnosis of malignancy, but also for identification of the hepatic origin of cells. A combination of the features of individual cells and of characteristic cellular patterns raised the diagnostic rates for well-, moderately, and poorly differentiated types of HCC to 90.5%, 100%, and 100%, respectively.     

Significance of histologic grading in the prognosis of ovarian tumors

The prognostic significance of a histologic grading system was studied by an analysis of pathological specimens from 73 patients with ovarian epithelial cancers and tumors of borderline malignancies (tumors of low malignant potential) collected over a period of 25 years. The survival probability of patients in each group was analyzed by a computer program based on the product limit of Kaplan and Meier. The histologic grading scheme based on the presence of papillary formations or glands versus the presence of solid tumor nests proved to be prognostically significant for patients with stage I and II disease. The other grading system, based on cytologic features, was able to stratify survival rates into three instead of two groups distinguished by the histologic grading system. The survival of patients with moderately and poorly differentiated tumors was essentially the same. No difference was found between the prognoses of patients with cytologic grades 3 and 4.     

Cytologic features and histologic correlations of microacinar and microtrabecular types of well-differentiated hepatocellular carcinoma in fine-needle aspiration biopsy

BACKGROUND: Well-differentiated hepatocellular carcinoma (HCC) in fine-needle aspiration (FNA) biopsy is characterized by trabeculae three or more cells thick wrapped by peripheral endothelium. The authors encountered another pattern that did not fulfill these classic criteria for malignancy yet was proven to be HCC in clinical follow-up. The objective of this study was to characterize the cytologic features of this pattern with histologic correlations. METHODS: Over a period of 6.5 years, 14 of 123 cases (11.4%) of HCC from 428 liver aspirates showed the unusual pattern. Their cytologic features were compared with 14 cases of nonneoplastic liver on FNA smears that were processed with Ultrafast Papanicolaou stain, and their histologic features were compared on cell blocks with hematoxylin and eosin stain and reticulin stain. RESULTS: The unusual type of well differentiated HCC in FNA smears was characterized by numerous, small hepatocytes with minimal nuclear atypia but reduced cytoplasm, grouped together in microacini of five or more cells and microtrabeculae one or more cells thick of irregular thickness with no apparent peripheral endothelium. Transgressing capillaries were found when the smears were inspected carefully. In histology nine cases that were the compact type of HCC, two cases that were the microacinar type of HCC, and three cases that were the microtrabecular type of HCC. All FNAs showed deficient reticulin framework. All 14 cases of nonneoplastic liver aspirate were characterized by the presence of large tissue fragments that were resistant to smearing. CONCLUSIONS: Well differentiated HCC may present as microtrabeculae of irregular thickness one or more cells thick with inapparent peripheral endothelium or as microacini mimicking neuroendocrine carcinoma.     

The polymorphic CAG repeat of the androgen receptor gene: a potential role in breast cancer in women over 40

Previous investigations into the relationship of CAG-repeat lengths in the androgen receptor (AR) gene to female breast cancer (BC) have yielded somewhat confusing results. Decreased AR transactivational activity lowers androgen:estrogen balance, and may thereby effect functional hyperestrogenicity. This may promote the pathogenesis of BC. To elucidate whether longer CAG repeats of the AR gene (AR), which correlate with lower transactivational activity of the AR, are associated with BC in women over 40, we examined the distribution of CAG-repeat lengths in BC tissue from this population. The BC tissue was histologically graded as: Grade 1, well differentiated (WD); Grade 2, moderately differentiated (MD); and Grade 3, poorly-differentiated (PD). Analysis showed significant differences as compared to controls when CAG lengths greater than 21 were examined, and that alleles with 26 repeats were 2.4-fold more frequent in BC samples than in constitutional samples from a normal population. A significant shift to greater CAG-repeat lengths, appeared in WD and MD tumors only. Our results give some indication as to the progression of BC by suggesting that hypotransactive ARs with long polyglutamine (polyGln) tracts may have a role in the initiation and/or progression of BC. PD tumors tended to have shorter than normal CAG-repeat lengths. In this case it is hypothesized that the ARs have now become hypertransactive, possibly coinciding with the estrogen resistance that is associated with PD tumors. Whether this shift is of germline or somatic origin was not clear, though the appearance in 14% of the BC samples of a third CAG-repeat length indicates that it may be somatic.     

Clinicopathological Correlation Study of Oral Squamous Cell Carcinoma in a Local Indian Population

Background: Oral squamous cell carcinoma (OSCC), the most common malignancy of the oral cavity, shows geographical variation with respect to the age, sex, site and habits of the population. The histolopathologic grade of the tumor is closely related to its tissue of origin. This study was conducted to establish the prevalence of OSCC in relation to patient sex, age, habits and sites of lesions. Materials and Methods: A total of 130 cases of histopathologically diagnosed OSCC were selected for the study, out of which 66, 38 and 26 were well (WD), moderately (MD)and poorly differentiated (PD), respectively. Sections were stained with haematoxylin and eosin and graded according to a modified Borders's system. Then statistically analyzed different grades of OSCC for correlations with other variables. Results: In our study the majority cases of OSCC were found in the 5th to 7th decades of life, males acconting for 53%. The most common site was the buccal mucosa and most cases had habit of tobacco use either in the form of chewing or smoking or both. When the different grades of OSCC were compared with different sites a statistically significant value was observed (P=0.029). Conclusions: The incidence of high grade PD is very much less in female patients but in males such lesions were common. In our location population the buccal mucosa is the most common site due to the tobbaco habits of the patients and majority cases of the buccal mucosa are WD whereas in tongue, floor of the mouth and palate PD are common.     

Prognostic significance of grading in lung adenocarcinoma

BACKGROUND:

Although grading has prognostic significance for many tumor types, a prognostically significant grading system for lung adenocarcinoma has not yet been established. The aim of this study was to evaluate histologic characteristics included in tumor grading systems, establish optimal cutoff values that have the strongest association with overall survival, and develop a grading system incorporating the histopathologic characteristics that the authors found to have prognostic significance in patients with lung adenocarcinoma.

METHODS:

The authors studied lung adenocarcinomas from 85 consecutive patients, and evaluated the percentage of solid pattern (as a reflection of tumor architecture), the degree of cytologic atypia, and the mitotic count.

RESULTS:

In univariate analysis, overall survival was associated significantly with sex (P = .045), age (P = .0008), tumor status (P < .0001), lymph node status (P = .02), solid pattern (P = .046), and cytologic atypia (P = .01), but not with mitotic count (P = .26). On the basis of optimal cutoff values, the authors found that a solid pattern ≥90% and severe cytologic atypia were the best discriminators of worse outcome. A grading score, computed as the sum of the architecture score and cytologic atypia score (2 = well differentiated, 3 = moderately differentiated, 4 = poorly differentiated), was a significant predictor of overall survival in univariate analysis (median overall survival times, 72.4, 39.5, and 8.7 months for well, moderately, and poorly differentiated adenocarcinoma, respectively; P = .0001). Moreover, grading was an independent predictor of survival in multivariate analysis (P = .002).

CONCLUSIONS:

The authors describe a grading system that incorporates the percentage of solid pattern and degree of the cytologic atypia that is an independent predictor of survival in patients with lung adenocarcinoma. Cancer 2010. © 2009 American Cancer Society.     

Lymphovascular invasion and lymph node metastasis rates in papillary adenocarcinoma of the stomach: implications for endoscopic resection

Background

Current Japanese gastric cancer treatment guidelines recommend the same endoscopic resection criteria for papillary early gastric cancer (EGC) and well-differentiated (WD) or moderately differentiated (MD) EGC. To evaluate the appropriateness of this recommendation, we compared the clinicopathological characteristics of papillary EGC with those of WD, MD, poorly differentiated (PD), and signet ring cell (SRC) EGC.

Methods

A total of 6710 patients who underwent radical gastrectomy for EGC were included. Clinicopathological characteristics of papillary EGC were retrospectively reviewed and compared with those in other EGC subtypes.

Results

Papillary EGC accounted for 1.9% (130/6710) of total cases. Patients with papillary EGC were older and showed a male predominance compared to patients with PD or SRC EGC. Papillary EGCs showed significantly higher submucosal and lymphovascular invasion rates than WD or MD EGC or PD or SRC EGC. However, the LN metastasis rate of papillary EGC was comparable to or lower than that in other EGC subtypes. LN metastasis rates in mucosal cancers were 1.5%, 1.1%, and 4.0%, and those in submucosal cancers were 9.4%, 11.9%, and 17.6% for papillary EGC, WD or MD EGC, and PD or SRC EGC, respectively. In multivariate analysis, lymphatic invasion and PD or SRC histology were the strongest risk factors for LN metastasis. Among 63 papillary EGC that met the curative endoscopic resection criteria, no case showed LN metastasis.

Conclusions

Endoscopic resection can be indicated for papillary EGC according to current guidelines. Given a considerable lymphovascular invasion rate, careful histological evaluation is required after endoscopic resection for papillary EGC.

     

Relationship between multicentric occurrence of hepatocellular carcinoma and histology of noncancerous hepatic tissue in patients with chronic hepatitis C.

The relationship between multicentric occurrence of hepatocellular carcinoma (HCC) and the histology of noncancerous hepatic tissue was investigated in 252 patients infected with hepatitis C virus (HCV) and surgically treated for HCC. One type of multicentric HCC had at least one tumor consisting of well-differentiated HCC, together with moderately or poorly differentiated HCC located in a separate region. The other type had an area of well-differentiated component around HCC with less differentiation in all occurrences. Noncancerous hepatic tissues were assessed using a histologic activity index score. Serum alanine aminotransferase (ALT) activity, the concentration of type 4 collagen, the grading score (severity of active hepatitis), and the staging score (degree of fibrosis) were significantly higher in patients with multicentric HCCs than in those without them. Platelet count was significantly lower in patients with multicentric HCCs. The prevalence of multicentric HCCs increased as the grading score and staging score increased. On univariate analysis, a low platelet count and high grading and staging scores were risk factors for multicentric HCCs. A high ALT activity and a high concentration of type 4 collagen tended to be risk factors. On multivariate analysis, high grading score and high staging score were independent risk factors. These findings indicate that active hepatitis and extensive fibrosis are responsible for the development of multicentric HCCs. Measurement of platelet count, ALT activity, and the concentration of type 4 collagen, and histologic assessment of noncancerous hepatic tissue provide information useful for estimation of the potential for multicentric carcinogenesis.     

Relationship between Multicentric Occurrence of Hepatocellular Carcinoma and Histology of Noncancerous Hepatic Tissue in Patients with Chronic Hepatitis C

The relationship between multicentric occurrence of hepatocellular carcinoma (HCC) and the histology of noncancerous hepatic tissue was investigated in 252 patients infected with hepatitis C virus (HCV) and surgically treated for HCC. One type of multicentric HCC had at least one tumor consisting of well-differentiated HCC, together with moderately or poorly differentiated HCC located in a separate region. The other type had an area of well-differentiated component around HCC with less differentiation in all occurrences. Noncancerous hepatic tissues were assessed using a histologic activity index score. Serum alanine aminotransferase (ALT) activity, the concentration of type 4 collagen, the grading score (severity of active hepatitis), and the staging score (degree of fibrosis) were significantly higher in patients with multicentric HCCs than in those without them. Platelet count was significantly lower in patients with multicentric HCCs. The prevalence of multicentric HCCs increased as the grading score and staging score increased. On univariate analysis, a low platelet count and high grading and staging scores were risk factors for multicentric HCCs. A high ALT activity and a high concentration of type 4 collagen tended to be risk factors. On multivariate analysis, high grading score and high staging score were independent risk factors. These findings indicate that active hepatitis and extensive fibrosis are responsible for the development of multicentric HCCs. Measurement of platelet count, ALT activity, and the concentration of type 4 collagen, and histologic assessment of noncancerous hepatic tissue provide information useful for estimation of the potential for multicentric carcinogenesis.     

Identification of genes associated with dedifferentiation of hepatocellular carcinoma with expression profiling analysis.

To identify the genes associated with dedifferentiation of hepatocellular carcinoma (HCC), gene expression profiles of HCCs of well-and moderately differentiated grades were compared by means of oligonucleotide arrays. One tumor showed a nodule-in-nodule appearance (NIN), which is occasionally observed in the course of progression of HCC from well to less differentiated grade, when an inner, moderately differentiated tumor (MD) develops sequentially from the outer, well-differentiated tumor (WD). Seventy-six genes were identified to be up-regulated more than 3-fold and 33 genes were down-regulated in the inner nodule in NIN. By statistical analysis of the profiles from 10 individual additional liver tumors, 5 WDs and 5 MDs, we were able to identify 12 genes, LAMA3, PPIB, ADAR, PSMD4, NDUFS8, D9SVA, CCT3, GBAP, ARD1, RDBP, CSRP2, and TLE1, with significantly elevated expression, and 4 genes, CP, IL7R, CD48, and PLGL, with decreased expression in MD. These selected genes were further validated using another 12 tumors, 5 WDs and 7 MDs, with semi-quantitative RT-PCR. We also applied neighborhood analysis to list the genes with high predictability values as most closely correlated with WD-MD distinction. Seven genes, ADAR, PSMD4, D9SVA, CCT3, GBAP, RDBP, and CSRP2, whose expression was elevated and one gene, IL7R, whose expression was decreased, were included among the top 50 predictor genes. These genes are likely to be associated with dedifferentiation of HCC and their identification may help to elucidate the mechanism of liver cancer progression.     

Identification of Genes Associated with Dedifferentiation of Hepatocellular Carcinoma with Expression Profiling Analysis

To identify the genes associated with dedifferentiation of hepatocellular carcinoma (HCC), gene expression profiles of HCCs of well-and moderately differentiated grades were compared by means of oligonucleotide arrays. One tumor showed a nodule-in-nodule appearance (NIN), which is occasionally observed in the course of progression of HCC from well to less differentiated grade, when an inner, moderately differentiated tumor (MD) develops sequentially from the outer, well-differentiated tumor (WD). Seventy-six genes were identified to be up-regulated more than 3-fold and 33 genes were down-regulated in the inner nodule in NIN. By statistical analysis of the profiles from 10 individual additional liver tumors, 5 WDs and 5 MDs, we were able to identify 12 genes, LAMA3, PPIB, ADAR, PSMD4, NDUFS8, D9SVA, CCT3, GBAP, ARD1, RDBP, CSRP2 , and TLE1 , with significantly elevated expression, and 4 genes, CP, IL7R, CD48 , and PLGL , with decreased expression in MD. These selected genes were further validated using another 12 tumors, 5 WDs and 7 MDs, with semi-quantitative RT-PCR. We also applied neighborhood analysis to list the genes with high predictability values as most closely correlated with WD-MD distinction. Seven genes, ADAR, PSMD4, D9SVA, CCT3, GBAP, RDBP , and CSRP2 , whose expression was elevated and one gene, IL7R , whose expression was decreased, were included among the top 50 predictor genes. These genes are likely to be associated with dedifferentiation of HCC and their identification may help to elucidate the mechanism of liver cancer progression.     

Cytologic scoring of endometrioid adenocarcinoma of the endometrium

BACKGROUND: Endometrial carcinoma is one of the most frequent malignancies in the female genital tract, and its incidence has been increasing in Japan. Histologic grade is an important factor for organizing treatment strategies, including hormone therapy, and for predicting the prognosis of the patient. The objective of this study was to evaluate the applicability and usefulness of cytologic scoring in assessing the morphologic differentiation of endometrioid adenocarcinomas of the endometrium using endometrial smears. METHODS: Sixty-four endometrial cytologic samples of endometrioid adenocarcinomas of the endometrium were used in this study. All patients underwent endometrial cytology before hysterectomy, and the diagnosis was confirmed by histologic examination of the extirpated uterus. Each cytologic specimen was scored according to a scoring system established by the authors. The cytologic grade based on those estimated scores was compared with the histologic grade and clinicopathologic parameters, respectively. RESULTS: The cytologic grade (CG) was correlated positively with the histologic grade. A high cytologic score was correlated with p53 mutation and myometrial invasion and was correlated negatively with estrogen receptor and progesterone receptor status. The concordance rates of cytologic grade with well differentiated (Grade 1), moderately differentiated (Grade 2), and poorly differentiated (Grade 3) histologic grades were 83.3% (35 of 42 tumors), 9.1% (1 of 11 tumors), and 100% (11 of 11 tumors), respectively. The total concordance rate was 73.4% (47 of 64 tumors). The best cut-off value for distinguishing histologic Grade 1 from the others was a cytologic score of 17, representing a sensitivity of 83% and a specificity of 81%. For distinguishing histologic Grade 3 from the others, the best cut-off value was a cytologic score of 20, representing a sensitivity of 100% and a specificity of 83%. CONCLUSIONS: The cytologic scoring system studied for endometrioid adenocarcinoma was useful for predicting histologic grade and tumor malignant potential.     

Percutaneous microwave coagulation therapy for patients with small hepatocellular carcinoma: comparison with percutaneous ethanol injection therapy

BACKGROUND: The authors compared the efficacy of percutaneous microwave coagulation therapy (PMCT) and percutaneous ethanol injection therapy (PEIT) in the treatment of patients with cirrhosis and a solitary nodular hepatocellular carcinoma (HCC) < or = 2 cm in greatest dimension. METHODS: Of 43 patients with well-differentiated HCC, 23 were treated with PMCT and 20 with PEIT. Of the 47 patients with moderately or poorly differentiated HCC, 25 were treated with PMCT and 22 with PEIT. In a retrospective, nonrandomized study, the prognoses of 90 patients during the 12-72 months preceding the study were analyzed according to histologic tumor grade. RESULTS: The overall 5-year survival rates for patients with well-differentiated HCC treated with PMCT (70%) and PEIT (78%) were not significantly different. No difference between the patterns of recurrence was observed. Among the patients with moderately or poorly differentiated HCC, overall survival with PMCT (5-year survival rate: 78%) was significantly better than with PEIT (5-year survival rate: 35%) (P = 0.03). Nine of 22 patients with moderately or poorly differentiated HCC treated with PEIT experienced recurrence in the original target subsegment. Only 2 of 25 patients treated with PMCT had a recurrence in the same subsegment as the initial tumor. CONCLUSIONS: PMCT may be superior to PEIT for the local control of moderately or poorly differentiated small HCC.     

The impact of conventional morphologic analysis on response rates and survival in patients with advanced head and neck cancers treated initially with cisplatin-containing combination chemotherapy

The response to initial treatment with cisplatin-containing combination chemotherapy as well as survival, were correlated with tumor differentiation (well, moderate or poorly differentiated) in 164 patients with advanced, untreated squamous cell carcinoma of the head and neck. Thirty-three percent of the tumors were graded as poorly differentiated, 59% moderately differentiated, and 8% were well differentiated. The overall clinical response rates were nearly equal for the three grades of differentiation: 79% for well differentiated, 86% for moderately differentiated, and 89% for poorly differentiated. The complete response rate was somewhat higher for poorly differentiated tumors: 46% as compared to 32% and 29% for moderately and well differentiated respectively, but the differences were not statistically significant. The median survival for each morphologic group was 22, 16, and 12 months for well differentiated, moderately differentiated and poorly differentiated tumor, respectively (P = 0.097). For patients achieving a complete clinical response to chemotherapy, there was a difference in survival when stratified according to degree of histologic differentiation. Patients who were complete responders and had well or moderately differentiated tumors attained 75% and 38% survival at 36 months, respectively, versus 19% for patients with complete response and poorly differentiated tumors (P = 0.064). The degree of differentiation of previously untreated squamous cell cancers of the head and neck does not conclusively predict tumor response to combination chemotherapy, but may reflect differences in natural history. Survival is improved in patients with differentiated tumors as compared to those with poorly differentiated tumors. Morphologic grading in patients achieving a complete response reveals a decrease in survival for patients with poorly differentiated tumors.     

Long-term outcomes for patients with solitary hepatocellular carcinoma treated by laparoscopic microwave coagulation

BACKGROUND: Although many reports on the treatment of hepatocellular carcinoma (HCC) by microwave coagulation have been published recently, none have incorporated data for the long-term therapeutic efficacy of laparoscopic microwave coagulation (LMC). In the current study, the efficacy of LMC was assessed. METHODS: The authors performed LMC under local anesthesia in 69 previously untreated patients with solitary HCCs < or = 4.0 cm in greatest dimension. The maximum diameter for the tumors averaged 22.6 +/- 7.4 mm. Long-time survival rate was evaluated according to the size and histologic grade of the tumor. RESULTS: The 5-year overall cumulative survival rate for the 69 patients was 63.9%. The 5-year overall survival rate for patients with well differentiated HCC was 78.9%, whereas patients with moderately or poorly differentiated HCC had a 5-year overall survival rate of 38.9%. The 5-year cumulative survival rate for patients with HCCs < or = 2.0 cm in diameter was 76.0%, and 56.3% for patients with HCCs >2.0 cm. Twelve patients (17.4%) showed local tumor recurrence during the follow-up period. Local tumor recurrence was observed in 6 of 21 patients with moderately or poorly differentiated HCCs (28.6%) and in 6 of 40 patients with well differentiated HCCs (15.0%). The 3-year cancer-free survival rate for patients with well differentiated HCC was 44.4%, whereas it was 12.2% for patients with moderately or poorly differentiated HCC. CONCLUSIONS: A major factor that influenced outcome in LMC was tumor cell differentiation. LMC procedures were best suited for treatment of well differentiated HCC.     

DNA fragmentation and cell proliferation correlated with tumor grade in patients with hepatocellular carcinoma

BACKGROUND: DNA fragmentation and cell proliferation in patients with hepatocellular carcinoma (HCC) have not been well described on fine-needle aspiration biopsies (FNABs). To investigate the contribution of apoptosis, a major mechanism of cell death, to the growth of HCC, the authors analyzed both apoptosis and cell proliferation in patients with HCC. METHODS: The authors studied 50 tumors from 50 patients with HCC: Ten tumors were well-differentiated HCC, 24 tumors were moderately differentiated HCC, and 16 tumors were poorly differentiated HCC. The detection of DNA fragments in situ using the terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin nick-end labeling (TUNEL) assay was applied to investigate active cell death (apoptosis), and the MIB-1 antigen was used to investigate cell proliferation. RESULTS: The TUNEL indices were 0.34 +/- 0.08, 082 +/- 0.30, and 2.0 +/- 0.95 in well-differentiated HCC, moderately differentiated HCC, and poorly differentiated HCC, respectively. The MIB-1 antigen labeling indices were 6.7 +/- 0.10, 13.2 +/- 3.4; and 26.9 +/- 6.5, respectively, in the same order of tumor differentiation. The differences in both TUNEL and MIB-1 labeling indices were significant between well differentiated HCC, moderately differentiated HCC, and poorly differentiated HCC, and a positive correlation was found between the TUNEL indices and the MIB-1 indices. CONCLUSIONS: Apoptosis (cell death) and cell proliferation increase as the grade of differentiation decreases in HCC, suggesting a rapid turnover of tumor cells in tumors with lower grades of differentiation, and apoptosis may play an important role in the growth of tumors in patients with HCC.