K. H. Lam

Small cell carcinoma of the esophagus

Ten cases of small cell carcinoma of the esophagus were studied clinicopathologically and immunohistochemically. Seven of the ten were also examined by electron microscopy. Histologically, six were oat cell type, four the intermediate cell type, and multiple histologic sections revealed squamous and glandular differentiations in small or minute areas of seven and two tumors, respectively. In four of the six polypoid tumors, the epithelium covering the tumor showed a malignant conversion accompanied by a proliferation of small anaplastic cells. Another one showed a cribriform pattern in a small area of the tumor. Argyrophilic tumor cells were seen in six cases and tumor cells immunohistochemically positive for ACTH and calcitonin were seen in six, and three cases, respectively. Neurosecretory granules were evident in three of the seven cases examined by electron microscopy. These findings suggest that a small cell carcinoma of the esophagus differentiates toward a squamous, glandular, or neurosecretory lesion, thereby supporting the idea of a totipotential stem cell origin of this tumor. The prognosis of patients with this tumor was poor, in accord with the evidence of aggressive lymphatic and blood vessel permeation.Background. Small cell carcinoma of the esophagus is regarded as having a poor prognosis with frequent systemic dissemination.

Anaplastic carcinoma of the thyroid

BACKGROUND Anaplastic thyroid carcinoma, albeit rare, is one of the most aggressive human tumors, with a dismal prognosis. METHODS Twenty-eight patients with anaplastic thyroid carcinoma were identified during the past 30 years to evaluate its clinicopathologic features and to document our experience in management. Potential risk factors for survival time were analyzed. RESULTS The usual presentation was that of a rapidly enlarging neck mass. Distant metastases were present in 50% of patients on presentation. Palliative resection was performed in 16 patients. The median survival was 38 days, and the 2-year survival rate was 4%. Among factors analyzed, patients selected for surgical resection, absence of distant metastases at presentation, young age, and tumor size <6 cm were associated with an increased survival time. Concomitant well-differentiated thyroid carcinoma and p53 overexpression were present in 12 of the 22 and 13 of the 19 specimens, respectively. CONCLUSIONS Patients with anaplastic carcinoma of thyroid have a dismal prognosis heralding imminent death. Surgical ablation followed by adjuvant therapy can provide palliation for selected patients only.

Staging Systems for Papillary Thyroid Carcinoma : a review and comparison

Objective:To find out the most predictive staging system for papillary thyroid carcinoma (PTC) currently available in the literature. Background:Various staging systems or risk group stratifications have been used extensively in the clinical management of patients with PTC, but the most predictive system for cancer-specific survival (CSS) based on distinct histologic types remains unclear. Methods:Through a comprehensive MEDLINE search from 1965 to 2005, a total of 17 staging systems were found in the literature and 14 systems were applied to the 589 PTC patients managed at our institution from 1961 to 2001. CSS were calculated by Kaplan-Meier method and were compared by log-rank test. Using Cox proportional hazards analysis, the relative importance of each staging system in determining CSS was calculated by the proportion of variation (PVE). Results:All 14 staging systems significantly predicted CSS (P < 0.001). The 3 highest ranked staging systems by PVE were the Metastases, Age, Completeness of Resection, Invasion, Size (MACIS) (18.7) followed by the new AJCC/UICC 6th edition tumor, node, metastases (TNM) (17.9), and the European Organization for Research and Treatment of Cancer (EORTC) (16.6). Conclusions:All of the currently available staging systems predicted CSS well in patients with PTC regardless of which histologic type from which they were derived. When predictability was measured by PVE, the MACIS system was the most predictive staging system and so should be the staging system of choice for PTC in the future.

Follicular Thyroid Carcinoma: The Role of Histology and Staging Systems in Predicting Survival

Objective:To evaluate the risk factors including tumor histomorphology for survival specific to follicular thyroid carcinoma (FTC) and to apply commonly employed staging systems in predicting survival for patients with FTC. Summary Background Data:FTC is usually analyzed collectively with papillary thyroid carcinoma (PTC) in risk group analysis. Risk factors and risk group analysis are important in the management of patients with FTC, although current published therapeutic guidelines call for total thyroidectomy followed by radioactive iodine (I131) ablation for all FTC patients. Methods:Over a 40-year period, 156 patients surgically treated for FTC with an average follow-up of 14.4 years were retrospectively studied after histologic reclassification according to the type and degree of invasiveness of the tumor. Potential risk factors for survival were calculated using multivariate analysis, and the prognostic accuracy of AMES risk group stratification, UICC/AJCC pTNM staging, Degroot classification, and MACIS scoring schemes in predicting survival was compared. Results:Seventeen (11%) patients had distant metastases at presentation, and bilateral thyroid resection was performed for 131 (84%) patients. Seventeen (11%) patients died of recurrent or metastatic disease. The overall and cancer-specific survival (CSS) rates at 10 years were 79% and 88%, respectively. None of the patients with minimally invasive (n = 49) or angioinvasive (n = 23) carcinomas died compared with 17 of 84 patients with widely invasive carcinomas (P = 0.0007). Using the Cox proportional hazards model, old age, the presence of distant metastases, and incomplete tumor excision were independent prognostic factors for survival. For patients who underwent curative treatment, old age and widely invasive carcinoma were risk factors for poor survival. All staging systems studied accurately predicted CSS, and the pTNM UICC/AJCC staging system yielded the best prognostic information. Conclusions:Commonly adopted staging systems can be applied specifically to patients with FTC. The distinction of FTC in minimally invasive and widely invasive carcinoma based on the extent of invasiveness rather than vascular invasion is important in identifying low-risk FTC patients for a more conservative management.

Insular and Anaplastic Carcinoma of the Thyroid: A 45-year Comparative Study at a Single Institution and a Review of the Significance of p53 and p21

OBJECTIVE To analyze the clinicopathologic features of a large cohort of patients with insular or anaplastic carcinomas treated at a single institution. SUMMARY BACKGROUND DATA Insular and anaplastic carcinomas of the thyroid, although uncommon, have more aggressive clinical behavior than well-differentiated carcinomas of the thyroid. In the literature, the incidence and features of these carcinomas have not been fully characterized. METHODS The authors reclassified 740 primary thyroid carcinomas diagnosed and treated between January 1, 1954, and December 30, 1998, to select those with features that met the histologic criteria of insular or anaplastic carcinoma. The clinicopathologic features of these carcinomas were studied and compared. The expression of p53 and p21 in these tumors was analyzed by immunohistochemistry. RESULTS Twenty-two patients (5 men, 17 women) with insular carcinoma and 38 patients (7 men, 31 women) with anaplastic carcinoma were found. Patients with insular carcinomas were younger (mean age 45 vs. 70 years) and had smaller tumors than those with anaplastic carcinomas (mean diameter 5 vs. 8 cm). Insular carcinomas were commonly mislabeled as other histologic subtypes, whereas anaplastic carcinomas might be overdiagnosed on pathologic examination. A history of longstanding goiter (>10 years) was noted in 27% of patients with insular carcinoma and 24% of patients with anaplastic carcinomas. Concomitant well-differentiated carcinomas of the thyroid were noted in 59% of patients with insular carcinoma and 39% of patients with anaplastic carcinoma. In anaplastic carcinomas, 13% of patients had concomitant insular carcinoma. Calcification or bone was noted in the stroma of 23% of patients with insular carcinomas and 47% of those with anaplastic carcinomas. The 10-year survival rates for patients with insular carcinoma and anaplastic carcinoma were 42% and 3%, respectively. Distant metastases were seen in 32% of patients with insular carcinoma and in 47% of patients with anaplastic carcinomas. In both types of carcinomas, metastatic tumors were often seen in bone and lung. Distant metastases were noted in a variety of organs in anaplastic carcinomas. In insular carcinoma, neither p53 nor p21 expression was present. In anaplastic carcinoma, p53 and p21 expression was identified in 69% and 3%, respectively. Concomitant expression of p53 and p21 was noted in one tumor. CONCLUSIONS Insular carcinoma and anaplastic carcinoma had distinctive clinicopathologic features, and recognition of these histologic variants is important for better management of these tumors in the future. p53 overexpression might have a role in dedifferentiation from insular carcinoma to anaplastic carcinoma.

Prognostic Factors in Papillary and Follicular Thyroid Carcinoma: Their Implications for Cancer Staging

Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) are two distinct histological types of thyroid carcinoma but have often been studied and staged as a collective group, known as differentiated thyroid carcinoma (DTC). However, this may not be an optimal approach to cancer staging. A total of 760 patients with DTC, comprising 589 (77.5%) with PTC and 171 with (22.5%) FTC, being managed at our institution from 1961 to 2001 were retrospectively reviewed. Their clinicopathological features, treatment modalities received, and postoperative outcome were analyzed. Both univariate and multivariate analyses were performed to identify prognostic factors related to cancer-specific survival (CSS) for PTC and FTC. There were statistically significant differences between PTC and FTC in terms of age ≥50 years at diagnosis (P = .040), tumor size (P < .001), lymph node metastases (P < .001), distant metastases (P < .001), extrathyroidal extension (P < .001), multifocality (P = .002), capsular invasion (P < .001), extent of thyroid resection (P < .001), radioiodine ablation (P < .001), and external-beam irradiation (P = .003). Although PTC and FTC had similar 10-year and 15-year CSS (P = .846), each possessed its own set of independent prognostic factors for CSS. Age at diagnosis and completeness of resection were independent prognostic factors in both PTC and FTC. There were marked differences in clinicopathologic features, treatment, and prognostic factors between the two histologic types of DTC. Different staging systems should be evaluated and validated for PTC and FTC individually in the future.

Adrenal pheochromocytoma remains a frequently overlooked diagnosis

BACKGROUND Adrenal pheochromocytoma is potentially lethal if undetected and is associated with long-term morbidity. METHODS Records of patients (11 men, 18 women) with confirmed pheochromocytoma were studied with respect to clinicopathological features and outcome. RESULTS Pheochromocytoma was diagnosed in 4 of 8,486 (0.05%) autopsies and accounted for 3 of the 4 immediate causes of death. Operative mortality occurred in 1 patient with undiagnosed tumor. Hypertensive-related complications occurred in 6 patients before diagnosis. Malignancy was documented in 7 patients with distant metastases (n = 4) or locally invasive tumors (n = 3). During a median follow-up of 4 years, 23 patients are alive and free of disease (79%). Four of the 6 patients (67%) who died had distant metastases compared with 2 of 23 patients (9%) without distant metastases (P = 0.04). Persistent hypertension and diabetes requiring treatment were present in 8 (35%) and 4 (17%) of 23 patients respectively. CONCLUSIONS Fatal complications preceded diagnosis in a significant proportion of patients with pheochromocytoma. The presence of distant metastases was associated with poor survival.

Papillary Microcarcinoma: Is There Any Difference between Clinically Overt and Occult Tumors?

Papillary microcarcinoma (PMC) is a subtype of papillary thyroid carcinoma (PTC) associated with excellent prognosis. However, clinical and biologic behaviors of PMC may vary considerably between tumors that are clinically overt and those that are occult. From 1964 to 2003, 185 of 628 patients with PTC were identified as having PMC, based on tumor size ≤1 cm. There were 110 overt and 75 occult PMCs detected based on clinical presentation. The clinicopathologic features, treatment, and long-term outcome of PMCs were evaluated and compared between the two groups. There were 37 men and 148 women with a median age of 45 years (range: 11–84 years). The median tumor size was 6.2 mm. Thirty-eight (21%) patients presented with cervical nodal metastases. Three (1.6%) had distant metastases and 5 (2.7%) underwent incomplete resection. Bilateral procedures were performed for 129 patients (70%) and 53 (29%) received postoperative I131treatment. During a mean follow-up of 8.2 years, 4 patients died of the disease and 13 developed recurrence. Clinically overt PMCs were significantly larger, were more likely to be multifocal, and more likely to lead to bilateral thyroidectomy. Extrathyroidal or lymphovascular invasion, nodal metastases, I131ablation, high-risk tumors, and postoperative recurrence occurred in overt PMC only. Patients with nodal metastases had a decreased survival and an increase in locoregional recurrence. Despite a relatively good prognosis in PMC, a distinction should be made between clinically overt and occult PMCs in which clinically overt PMC should be managed according to tumor risk profile and clinical presentation.

Prognostic implication of proliferative markers MIB-1 and PC10 in esophageal squamous cell carcinoma.

Proliferative markers are related to tumor behavior. The commonly used markers are proliferating cell nuclear antigen (PCNA) and Ki‐67. The aim of this study is to evaluate the usefulness of MIB‐1 (for Ki‐67) and PC10 (for PCNA) in the assessment of the clinicopathologic features and prognosis in patients with esophageal squamous cell carcinoma.

Prevalence of HPV infection in esophageal squamous cell carcinoma in Chinese patients and its relationship to the p53 gene mutation

Human papillomavirus (HPV), in particular types 16 and 18, is positively associated with anogenital cancers and may be an important etiologic factor in their pathogenesis. The goal of our study was to investigate the role of HPV infection in the pathogenesis of esophageal squamous cell carcinoma (ESCC) and its relationship with the p53 mutation. We have examined ESCC collected from Sichuan, China, for the presence of HPV infection and p53 mutation. The presence of HPV DNA was detected by PCR‐Southern analysis while the p53 mutation was analyzed by PCR‐SSCP. High‐risk HPV (types 16 and 18) DNA was detected in 32 out of 152 cases of ESCC examined. In contrast, HPV DNA was not detected in normal esophageal tissues excised from the distant end (tumor free) of resected ESCC. Mutation of the p53 gene was detected in 22 out of 55 cases of ESCC. The distribution of the 22 p53 mutation was: 5 in exon 5, 1 in exon 6, 5 in exon 7, 10 in exon 8 and 1 in exon 10. The p53 mutation was detected at a significantly lower rate in ESCC with HPV infection. Our results support a role of HPV infection in the pathogenesis of ESCC from a high‐incidence area. Int. J. Cancer 72:959–964, 1997.