Thymoma: a clinicopathologic study based on the new World Health Organization classification

OBJECTIVE: This study explored the relationship between the histologic subtype of thymoma according to the new World Health Organization histologic classification and the clinical findings, as well as the prognostic significance of the classification. METHODS: A total of 130 patients with thymoma, who underwent resection at the National Cancer Center Hospital, Tokyo, from 1962 to 2000, were studied retrospectively. The histologic subtype of thymoma was determined according to the new World Health Organization histologic classification. The stage was also determined according to a modified Masaoka's classification as stage I, II, III, IVa, or IVb. To determine the factors that may affect the prognosis of thymoma, a multivariate analysis with Cox's proportional hazards regression model was performed. RESULTS: The distribution of histologic subtype was type A (n = 18), type AB (n = 56), type B1 (n = 15), type B2 (n = 29), and type B3 (n = 12). A close correlation was seen between the histologic subtype and stage (P =.000). The overall survivals at 5 and 10 years were 92% and 91%, respectively. The 5- and 10-year survivals according to stage were 100% and 100% (stage I, n = 40; stage II, n = 54), 81% and 76% (stage III, n = 25), and 47% and 47% (stage IV, n = 11), respectively. The difference in survival between stage III and stage IV was significant (P =.000). Patients with type A or AB thymoma demonstrated a 100% survival at both 5 and 10 years. Recurrences were seen in 12 patients with complete resection. According to a multivariate analysis, tumor size (P =.001), completeness of resection (P =.002), histologic subtype (P =.011), and stage (P =.00) were significant prognostic factors. CONCLUSION: The World Health Organization histologic classification significantly correlated with the clinical stage. Tumor size, completeness of resection, histologic subtype, and stage predicted the prognosis of thymoma.     

Peribronchiolar metaplasia: a common histologic lesion in diffuse lung disease and a rare cause of interstitial lung disease: clinicopathologic features of 15 cases

Peribronchiolar metaplasia (PBM) is a histologic lesion consisting of peribronchiolar metaplasia (PBM) of bronchiolar-type epithelium. Although widely recognized, PBM has received little attention in the pathologic literature and is not known to have clinical significance. We identified 15 cases in which PBM was the only major histologic finding in surgical lung biopsies from patients with interstitial lung disease (PBM-ILD), and we reviewed the clinical, imaging, and pathologic findings. The mean age was 57 years (range, 44-74 years) with 13 females and 2 males. One patient had been a welder with fume and asbestos exposure; another had pigeon exposure. Smoking history was available for 13 patients: three current smokers, one cocaine user, two former smokers, and seven never smokers. Three patients had collagen vascular disease. One had elevated serum antinuclear antibody titers. Pulmonary function data were available for 10 patients: one obstructive, five restrictive, two mixed obstructive and restrictive, and two normal. Computerized tomography in 7 patients showed mosaic attenuation in 3 patients and air trapping in 1 patient; no bronchiectasis, septal lines, or honeycombing were seen in any cases. All 11 patients with available follow-up are alive; 4 of them have experienced symptomatic improvement (follow-up, 0.6-6.9 years; mean, 2.4 years). PBM was found focally in other interstitial lung diseases, which were assessed for this lesion: 59% of usual interstitial pneumonia (17 of 29), 50% of nonspecific interstitial pneumonia (10 of 20), desquamative interstitial pneumonia (3 of 6), hypersensitivity pneumonitis (9 of 18), and 11% of respiratory bronchiolitis (2 of 18). In summary, PBM is a common histologic finding in various interstitial lung disorders. It is rarely the sole major lung biopsy finding in patients presenting with interstitial lung disease (PBM-ILD). Patients are mostly older women, with mild symptoms and CT findings. Survival appears to be favorable.     

Laparoscopic cholecystectomy for elderly patients: gold standard for golden years?

HYPOTHESIS: Laparoscopic cholecystectomy (LC) has known physiological benefits and positive socioeconomic effects over the open procedure. Although recent studies have questioned the technique's efficacy in elderly patients (>65 years), we hypothesize that LC is safe and efficacious in that patient group. METHODS: Five thousand eight hundred eighty-four consecutive patients (mean age, 40 years; 26% male) underwent an attempted LC (conversion rate, 5.2%) from 1991 to 2001 at a teaching institution. Of these, 395 patients (6.7%) were older than 65 years. Analysis included patient age, sex, American Society of Anesthesiologists classification, conversion rate, morbidity, mortality, and assessment of results over time. RESULTS: Elderly patients were predominantly male (64%). Septuagenarians had a 40% incidence of complicated gallstone disease, such as acute cholecystitis, choledocholithiasis, or biliary pancreatitis, and octogenarians had a 55% incidence. Overall mortality was 1.4%. The conversion rate was 17% for the first 5 years of the study period and 7% for the second half. The conversion rate was 22% for patients with complicated disease and 2.5% for patients with chronic cholecystitis. Average hospital stay decreased from 10.2 days to 4.6 days during the first and second half of the study period, respectively. CONCLUSIONS: The results of LC in patients aged 65 to 69 years are comparable with those previously reported in younger patients. Patients older than 70 years had a 2-fold increase in complicated biliary tract disease and conversion rates, but a low mortality rate (2%) compared with results of other authors (12%), despite an increase in American Society of Anesthesiologists classification. Increased technical experience with LC favorably affected outcomes over time. Early diagnosis and treatment prior to onset of complications are necessary for further improvement in the outcomes of elderly patients undergoing LC.     

The pathology of malignant fibrous histiocytoma of bone. A study of 130 patients

Since 1927, 130 patients with well-documented malignant fibrous histiocytoma of bone have been diagnosed and treated at Memorial Hospital for Cancer and Allied Diseases. This sarcoma is 10 times less frequent than osteogenic sarcoma in this hospital. It most commonly occurred spontaneously (72%), whereas in the rest (28%) it followed previous radiation or various pre-existent osseous conditions, most often Paget's disease. The appendicular skeleton was the commonest site of involvement. The majority of the patients were middle-aged or older adults with a mean of 40.5 years of age; only 21.5% were 21 years or younger. Histologically, the lesions were subclassified as fibrous (62%), histiocytic or xanthomatous (30%), and malignant giant cell tumor (8%) variants. Older patients were more likely to have a secondary malignant fibrous histiocytoma, especially following radiation or Paget's disease. Overall survival estimates at 2 years and 5 years were 71% and 53%, respectively. Survival was not dependent on the histologic subtype of the lesion, but was strongly influenced by the histologic grade of malignancy. Important prognostic factors were the age of the patients and whether the lesions were primary de novo or secondary sarcomas: the older patients and those with secondary lesions did substantially worse.     

Radical surgery for malignant pleural mesothelioma: results and prognosis

The role of surgical treatment for malignant pleural mesothelioma (MPM) continues to be controversial. We carried out a retrospective review of the prognosis in patients who had radical surgery for MPM. Of 87 consecutive patients on whom surgical exploration for biopsy-proven MPM was performed, 31 patients underwent extrapleural pneumonectomy (EPP) and 34 patients underwent pleurectomy/decortication (P/D). Sixty-five patients having EPP or P/D included 58 men (89%). The median age was 60 years (range 35-78) and the histologic type was epithelial in 48 patients (74%). IMIG staging classification was p-stage I disease in eight patients (12%), p-stage II in 13 (20%), p-stage III in 40 (62%) and p-stage IV in 4 (6%). Operative mortality was 3.2% for EPP and none for P/D. The median and 3-year survivals after EPP were 13 months and 33% whereas those after P/D were 17 months and 24%, respectively. A multivariate analysis demonstrated that older age (P=0.0467), non-epithelial histology (P=0.0057) and p-stage III-IV disease (P=0.0019), but not gender, side, surgical procedure, were significant independent negative prognostic factors. Although P/D appears to be acceptable in early stages, we encourage EPP, en bloc resection without entering the pleural cavity with intent for curability, which provides oncologically complete resection of all disease.     

Clinical outcome of epithelial tumors of the thymus

OBJECTIVE AND METHODS: We retrospectively reviewed treatment and clinical outcome of thymic epithelial tumors of 64 patients over a 20-year period. Clinical staging of the tumor was done by according to Masaoka classification. Histological diagnosis of the tumors was done by according to the second edition of the WHO histologic classification system for thymic epithelial tumors. Survival rate was calculated after Kaplan-Meire method. RESULTS: Median age of patients was 53.7 years (ranged from 16 to 81). There were 30 men and 34 women. Eighteen patients had auto-immuno diseases. Sixty-two patients underwent surgery. In 57 patients resection was complete (extended thymo-thymectomy), but in the other five incomplete. The operative approach was median sternotomy in 51 patients and video-assisted thoracoscopic surgery in 6. Stage II to IV patients had postoperative mediastinal irradiation. Stage III to IV patients had postoperative cisplatin (CDDP) based chemotherapy. Inoperable patients were treated by chemo-radiotherapy. There were 42 stage I, 7 stage II, 11 stage III, 3 stage IV a, 1 stage IV b. The 5-year/10-year survival rates were 93%/89%, 71%/71%, 68.5%/--in patients with stage I, II and III. There were 5 type A tumors, 8 type AB tumors, 11 type B1 tumors, 11 type B2 tumors, 9 type B3 tumors, 11 type C tumors, the respect 5-year survival rates were 100%, 100%, 87.5%, 60%, 85.7% and 90%. Masaoka stage II to IV patients classified in B2, B3 and C type except one case. CONCLUSION: Histologic type B2, B3 and C tumors may reflect the invasive nature. Masaoka staging system and the WHO histologic classification may help the assessment and treatment of patients with thymic epithelial tumor.     

WHO histologic classification is a prognostic indicator in thymoma

BACKGROUND: The histologic classification of thymoma has remained a subject of controversy for many years. In 1999, the World Health Organization Consensus Committee published a histologic typing system for tumors of the thymus. METHODS: We reclassified a series of 100 thymomas resected at Tokushima University Hospital and four affiliated hospitals in Japan between 1973 and 2001 according to the World Health Organization histologic classification and reported its clinicopathologic relationship and prognostic relevance. RESULTS: There were 8 type A, 17 type AB, 27 type B1, 8 type B2, 12 type B3, and 28 type C thymomas. The frequency of invasion to neighboring organs increased according to tumor subtype in the order A (0%), AB (6%), B1 (19%), B2 (25%), B3 (42%), and C (89%). There was no recurrence in patients with type A, AB, or B2 thymoma. The recurrence rates of patients with B1, B3, or C thymoma were 15%, 36%, and 47%, respectively. The disease-free survival rates were 100% for types A and AB, 83% for types B1 and B2, 36% for type B3, and 28% for type C thymoma at 10 years. There were significant differences in disease-free survival between types A and AB and types B1 and B2 (p = 0.0436), and between type B3 and type C (p = 0.042). By multivariate analysis, only Masaoka clinical stage (p = 0.002) showed significant independent effects on disease-free survival. The 10-year survival rates of types A and AB, types B1 and B2, type B3, and type C thymoma were 100%, 94%, 92%, and 58%, respectively. CONCLUSIONS: The current study confirmed the World Health Organization histologic classification as a good prognostic factor.     

Premature femoral head growth plate closure in Perthes' disease]

The study population consisted of 311 patients (50 female and 261 male) who had reached skeletal maturity at last follow up (361 hips). The mean age at the onset of symptoms was 6 years and 10 months (range: 2.5-13 years). All patients were treated by containment methods (bed rest and traction in abduction, brace, Petri cast, varus osteotomy, Salter osteotomy and shelf operation). Premature growth plate closure was estimated according to Bowen (central and lateral). Necrosis of the femoral head was classified according to Herring and Catterall, late results according to Stulberg and Mose and leg length discrepancy on scanograms. Article-trochanter distance (ATD) was estimated according to the Edgren methods. Premature femoral head growth plate closure was found in 61 hips (central--41 and lateral--20). Statistical analysis did not reveal any correlation between the gender and type of treatment and premature growth plate closure. The central pattern of growth plate closure was more often seen to 6 years of age at the onset and the lateral over 9 years of age at the onset (p = 0.0176). Premature growth plate closure was observed more often in Herring group C and Catterall group 4 (p = 0.0001). Disturbances in femoral head sphericity according to Mose increased (except with bilateral Perthes' disease) and ATD decreased in patients with premature growth plate closure. Also premature growth plate closure increased the leg length discrepancy in Perthes' disease. Thirty two (52.5%) hips with abnormal physeal growth were classified into type I or II according to Stulberg classification, 16 (26.2%) into type III and 13 (21.3%) into type IV or V. Premature growth plate closure in Perthes' disease is more common in huge necrosis of the femoral head. The central pattern of growth plate closure is more often in younger children (to 6 years of age) and the lateral in older (over 9 years of age). With abnormal physeal growth the greater trochanter overgrow and ATD decreased, the leg length discrepancy and disturbances in sphericity of the femoral head increased. Premature growth plate closure increased satisfactory and poor results according to Stulberg classification.     

Breast cancer in the young patient

Patients under 40 years of age comprise about 5 per cent of the overall breast cancer population. These patients are often considered to have a more aggressive disease and are often treated differently as well. A review was performed of all breast cancer patients reported in the American College of Surgeons Cancer Database from 1998 to 2005. The study cohort included all patients less than 40 years of age. Data collected included stage at time of diagnosis, histologic type, and initial treatment performed. These data were then compared with those of patients age 40 or older. The 70,437 cohort patients identified comprised 5.0 per cent of all breast cancer patients reported. There was a statistically significant difference in stage at the time of presentation: 20 per cent of younger patients presented with advanced disease (stage III or IV) versus 13.5 per cent of older patients. A significantly greater percentage of younger patients also presented with infiltrating ductal carcinoma as opposed to the older population (76.9% vs 67.9%). A significantly greater percentage of young patients was treated with mastectomy when compared with the older population (47.7% vs 36.7%, respectively). This difference persisted even when data were controlled for stage. The younger breast cancer patient presents with more advanced disease, suggesting either a more aggressive disease or a greater delay in diagnosis. Also, at all stages, the young patient tends to be treated more "aggressively" surgically, suggesting that the prevailing concept that breast cancer is a "worse" disease in the young may be directing treatment options and patient choices.     

Emergency surgery results in life-threatening thoracic aortic disease

OBJECTIVE: Emergency surgery for thoracic aortic aneurysm continues to involve high mortality. We review our experience in emergency surgery for life-threatening thoracic aortic disease. METHODS: Between September 1994 and June 2000, 65 consecutive patients--38 men and 27 women aged 18 to 84 years (mean: 64.3 years)--underwent emergency surgery for thoracic aortic disease. Of these, 40 (61%) were treated for acute type A dissection, 16 (25%) for aortic rupture, and 9 (14%) for impending aneurysmal rupture. Ascending aorta repair was conducted in 21, aortic arch repair in 30, distal arch repair in 2, descending aorta repair in 9, and thoracoabdominal aorta repair in 3. Of the 65, 42 were under 70 years old and 23 were 70 years of age and older. RESULTS: Overall, 8 (12%) died in the hospital--3 (7.5%) of acute type A dissection, 3 (19%) of ruptured aneurysm, and 2 (22%) of impending rupture. Of these, 3 (7.1%) were younger than 70 years and 5 (22%) 70 years and older. The following perioperative factors significantly influenced hospital mortality: pump time (p = 0.019), postoperative severe cardiac failure (p = 0.006), postoperative respiratory failure (p = 0.045), and postoperative acute renal failure (p = 0.0007). Of the 57 survivors followed up for an average of 2.8 years (1 month to 6 years), 3-year survival was 73% overall--88% in patients younger than 70 years and 38% in those 70 years and older (p = 0.0004). Seven of the 9 patients suffering strokes during surgery died in the hospital (2) or after discharge (5). Overall hospital and late deaths involved 2 of 4 patients younger than 70 years and all of 5 patients 70 years and older. CONCLUSION: The majority of patients undergoing emergency surgery for life-threatening thoracic aortic disease can undergo graft replacement with acceptable mortality, morbidity, and late survival, but early and late mortality for patients older than 70 remains extremely high.     

Pathologic identification of poor prognosis stage I (T1N0M0) cancer of the breast.

Twenty to 40% of Stage I(T1N0M0) cancers of the breast recur in ten years. This is an attempt to identify those patients in whom the disease is likely to recur. On the basis of a study of the histologic changes in the tumor and treatment failures poor prognosis was associated with several histological characteristics: poor cytologic differentiation; lymphatic permeation; blood vessel invasion and invasion of the tumor into the surrounding soft tissue. This classification was then applied to 363 cancers of the breast seen over a five year period and followed three to eight years. There were 203 Stage I (T1N0M0) tumors in the group. Ninety-four of the 203 Stage I tumors had one to four of the above histologic characteristics; 109 had none. Among the 109 patients characterized as good risks there were two treatment failures (2%). In the group of 94 with any high risk histologic features there were 47 treatment failures (50%) which were statistically significant (p = 0.001). The histologic changes had a cumulative effect on the degree of malignancy of the tumor. Pathologic changes in the tumor identified those patients whose Stage I (T1N0M0) tumors were likely to recur.     

Subclassification of autoimmune pancreatitis: a histologic classification with clinical significance

Autoimmune pancreatitis (AIP) is a chronic inflammatory disease of the pancreas. Examination of pancreatic resection specimens from patients with AIP has shown that there are 2 subclasses of this disease. However, there is no widely accepted pathologic classification scheme and the clinical significance of such a classification remains to be established. In this study, we revisited the subclassification of AIP and examine whether this provides clinically and prognostically meaningful information. We evaluated 29 pancreatic resection specimens from patients with AIP. Demographic, clinical, and imaging data were recorded, as was evidence of extrapancreatic manifestations. In addition to a detailed and semiquantitative histologic evaluation, immunohistochemistry for IgG4 was performed on pancreatic and extrapancreatic tissues. We also evaluated 48 consecutive cases of chronic pancreatitis, not otherwise specified. The resected specimens could readily be subclassified into 2 subtypes: type 1 (n=11) and type 2 (n=18). In comparison with patients with type 2 disease, patients with type 1 disease were significantly more likely to be males (P=0.09), older (P=0.02), and present with jaundice (P=0.01), and less likely to be associated with abdominal pain (P=0.04). On imaging, the pancreatic tail cut-off sign was exclusively seen in patients with type 2 disease (4 of 10 cases). Hypercellular inflamed interlobular stroma was unique to type 1 pattern (91%), whereas significant ductal injury in the form of microabscesses and ductal ulceration was almost exclusively seen in type 2 pattern (78%). Eight of 10 patients with a type 1 pattern had evidence of a systemic disease. Three patients with type 2 disease had recurrent episodes of pancreatitis after their pancreatic resection. In comparison with the cohort of chronic pancreatitis, not otherwise specified, type 2 AIP cases were less likely to be associated with a history of alcohol abuse, and showed significantly more foci of periductal inflammation and neutrophilic microabscesses. Our review of pancreatic resection specimens shows 2 histologically distinct forms of AIP. Our data support the concept that type 1 AIP is a systemic disease and is the pancreatic manifestation of IgG4-related systemic disease. Type 2 disease is confined to the pancreas. The intensity of the periductal inflammatory infiltrate and the presence of ductal neutrophilic abscesses are features that assist in distinguishing type 2 AIP from chronic pancreatitis, not otherwise specified. Although imperfect, clinical and imaging features may help distinguish the 2 subtypes of AIP. On the basis of these significant differences between the 2 types of AIP, we advocate the position that all subsequent studies attempt to substratify their patients into these 2 groups.     

IgA nephropathy in Korea: a morphological and clinical study

IgA nephropathy (IgA N) is the most common type of primary glomerulonephritis (27.5%) in South Korea and leads to renal failure in a significant number of cases. To evaluate the possible prognosticators of this disease, renal biopsy material from 142 Korean patients with IgA N was studied by light-, electron- and immunofluorescent microscopy, and a clinicopathologic correlation was made. Modified classification of Meadow et al. [1972] for Henoch-Schoenlein nephritis was adopted for the histologic grading of glomerular lesions. Twenty-three biopsies (16.2%) exhibited histologic grades IV and V lesions in association with high levels of proteinuria, serum creatinine and blood pressure and a low frequency of gross hematuria when compared to the remaining 119 biopsies with histologic grades I to III lesions. Ninety-one patients were followed for one to 6.5 years (mean, 3.4 years). Seventeen patients (18.7%) had chronic renal insufficiency, of whom eleven eventually showed endstage renal failure. More than 70% of the patients with histologic grades IV and V exhibited progressive renal disease, whereas patients with grades I to III lesions had a benign course (p less than 0.0005). These results suggest that histologic grading may be the best index to predict the present state or the subsequent progression of the lesion in IgA N.     

Bronchial carcinoids. Review of 124 cases

A total of 124 patients with bronchial carcinoid were seen at Memorial Sloan-Kettering Cancer Center between 1949 and 1983. Of these, 68 were female and 56 were male. The age range was 12 to 82 years (median 55 years). Eleven of the tumors were incidental pathological findings at autopsy or operation and were excluded from survival data determinations. At the time of diagnosis, 82 patients had disease confined to the lung or bronchus, 19 had regional lymph node metastases, and 12 had distant metastases. Patients with distant metastases were more commonly male and smokers, and their tumors were mainly atypical carcinoids histologically, compared with those of patients with localized disease. Patients with distant disease were treated with external radiation and/or chemotherapy, and their median survival was 8 months. Of the 101 patients with disease localized to one hemithorax, endobronchial resection was performed in six and pulmonary resection in 95 (pneumonectomy 14, bilobectomy nine, lobectomy 52, sleeve resection five, segmentectomy 15). Recurrence following endobronchial resection was observed in four of six patients. Disease-free actuarial survival (calculated by the Kaplan-Meier method) following pulmonary resection was 92% at 5 years and 77% at 10 years. Factors predisposing to recurrence were tumor size greater than 3 cm (p less than 0.004), an atypical carcinoid on histologic study (p less than 0.001), and regional lymph node metastases (p = 0.01). Disease-free survival at 5 and 10 years in 19 patients who had regional lymphatic metastases was 74% and 53%, compared with 96% and 84% in those without lymphatic metastases. We conclude that (1) carcinoid tumors are malignant and 10% of patients present with metastases and (2) for patients with clinically localized tumors, the prognosis is determined by the size and histologic features of the tumor and the status of the regional lymph nodes, which must be assessed at thoracotomy.     

Clinicopathologic features of rhabdomyosarcoma of gynecologic origin in adults

Rhabdomyosarcoma (RMS) is the most common soft tissue tumor found in children. Up to 20% of RMS tumors in children originate in the genital tract making this the second most common site. RMS of gynecologic origin in adults is much less common. The purpose of this study was to describe the clinical and pathologic features of RMS of the adult female genital tract. We reviewed the histologic slides of women 16 years of age and older and included them in our study if they contained the classic histologic features of RMS as described by the 2002 World Health Organization classification of tumors. Rhabdomyoblastic components present in other established malignancies were not studied. We identified 15 patients, with a median age of 48 years (range, 16 to 69). Eleven (73%) of the tumors were of embryonal histology (cervix, 8; uterus, 2; and ovary, 1). Of the remaining 4 tumors, 2 were of alveolar (vulva) and 2 of pleomorphic (uterus, 1; fallopian tube, 1) histologic subtype. The majority (79%) of these patients presented with locoregional disease and had surgery as their primary intervention (73%). The median progression-free survival (PFS) and disease-specific survival was 9 months [95% confidence interval (CI), 1-24] and 21 months (95% CI, 14-28), respectively. The 5-year disease-specific survival was only 29%. There was a significant difference in PFS between cases of embryonal compared to cases with nonembryonal histology (19 vs. 3 mo, respectively) (P=0.04). Adult RMS of gynecologic origin presents with locoregional disease and most are morphologically similar to pediatric RMS; however, adult RMS behaves more aggressively, with worse overall survival. It is unclear whether these divergent outcomes are the result of differences in clinical management or because these tumors are biologically distinct.     

An analysis and evaluation of anesthetic consultations for patients undergoing elective surgery

We reviewed 212 patients whom we consulted before elective surgery concerning their indications of operation and anesthetic risks for the last 18 month periods. Patients' ages were between 6 months to 89 years old, and 46% of the patients consulted were over 60 years of age. Main medical problems related to anesthetic risks included cardiovascular problems (36% of patients), respiratory problems (14%), the abnormality of metabolism or endocrine (8%), hepatic dysfunction (8%), and so on. Most of the patients with ischemic heart disease, hypertension, dysrhythmia, or dysfunction of respiratory system, were over 60 years of age. Those with diabetes mellitus, dysfunction of liver or kidney, or anemia were over 40 years of age. Those with convulsion or congenital heart disease were under 19 years of age. In attempting anesthetic evaluations, patients were assessed according to ASA physical status classification; class I (3%), class II (56%), class III (36%), class IV (5%). Although there was no patient who had intraoperative cardiac arrest or death related to anesthesia, postoperative mortality within 3 months were 19% for ASA class III patients and 60% for class IV. And all ASA IV patients who received their operation died postoperatively. In patients who were classified as ASA III or IV, we feel it is better to add more detailed classification such as Goldman's classification in addition to physical status classification of ASA for preanesthetic assessments of patients, because the majority of patients were elderly with life-threatening complications of cardiovascular and/or respiratory systems.     

Carcinoma of the ampulla of Vater: comparative histologic/immunohistochemical classification and follow-up

A broad histomorphologic spectrum of ampullary carcinomas of Vater make a reproducible histologic classification difficult. Using cytokeratin immunohistochemistry, we present a new classification of ampullary carcinomas and analyze their clinical significance. Fifty-five invasive carcinomas of Vater's ampulla were histologically classified into pancreaticobiliary, intestinal, and other types. Serial sections of all carcinoma specimens were additionally stained with antibodies to cytokeratins (CK7, CK20), apomucins (MUC1, MUC2, MUC5AC), CEA, CA19-9, Ki67, and p53. Follow-up of patients from 4 months to 22 years after surgery (mean interval, 51.6 months) was evaluated. Most carcinomas of the ampulla of Vater were of immunohistochemically pancreaticobiliary type (iPT, CK7+, CK20-; 54.5%) or intestinal type (immunohistochemically intestinal type [iIT], CK7-, CK20+; 23.6%). Some carcinomas of immunohistochemically "other" type (iOT both CK7+ and CK20+ or CK7- and CK20-; 21.8%) had precursor lesions of iIT or iPT. Carcinomas positive for MUC2 or CEA were associated with iIT (MUC2, P < 0.001; CEA, P = 0.003), whereas MUC5AC-positive carcinomas were related to iPT (P = 0.005). Our classification based on cytokeratin-immunohistochemistry correlated well with the histologic classification according to published criteria (kappa-coefficient = 0.398; P < 0.001). Furthermore, histologically unusual types could be histogenetically related to pancreaticobiliary duct mucosa or intestinal mucosa. Therefore, all 4 signet-ring cell carcinomas were iIT carcinomas. Thus, cytokeratin immunohistochemistry allows a reproducible, histogenetically based categorization of ampullary carcinomas. However, neither histopathologic nor immunohistochemical subgroups significantly correlated with clinical outcome in our German collective. The overall survival was significantly shorter in males (P = 0.032) and patients with positive nodal stage (N1 < N0; P = 0.0025).     

Inflammatory myofibroblastic tumor: comparison of clinicopathologic, histologic, and immunohistochemical features including ALK expression in atypical and aggressive cases

Inflammatory myofibroblastic tumor (IMT) is a neoplasm of intermediate biologic potential. In this study, we report a subset of IMTs with histologic atypia and/or clinical aggressiveness that were analyzed for clinicopathologic features, outcome, and immunohistochemical expression of anaplastic lymphoma kinase (ALK) and other markers to identify potential pathologic prognostic features. Fifty-nine IMTs with classic morphology (5 cases), atypical histologic features (21 cases), local recurrence (27 cases), and/or metastasis (6 cases) were studied. Immunohistochemistry was performed for ALK1 and other markers (Mib-1, c-Myc, cyclin D1, caspase 3, Bcl-2, Mcl-1, survivin, p27, CD56, p53, MDM-2) using standard techniques. The 59 IMTs had an age at diagnosis ranging from 3 weeks to 74 years (mean 13.2 y, median 11 y, 44% in the first decade). The mean tumor size was 7.8 cm. Sites included the abdomen or pelvis in 64%, lung in 22%, head and neck in 8%, and extremities in 5%. The follow-up ranged from 3 months to 11 years, with a mean of 3.6 years and a median of 3 years. Thirty-three patients had local recurrences, including 13 with multiple local recurrences and 6 patients with both local recurrences and distant metastases. Six patients died of disease, 5 with local recurrences, and 1 with distant metastases. Histologic evolution to a more pleomorphic cellular, spindled, polygonal, or round cell morphologic pattern was observed in 7 cases. Abdominal and pelvic IMTs had a recurrence rate of 85%. Recurrent and metastatic IMTs were larger, with mean diameters of 8.7 and 11 cm, respectively. Cytoplasmic ALK reactivity was seen in 56%. ALK-negative IMTs occurred in older patients (mean age 20.1) years and had greater nuclear pleomorphism, atypia, and atypical mitoses. All 6 metastatic IMTs were ALK-negative. Nuclear expression of p53 was detected in 80% of IMTs overall, but in only 25% of the metastatic subset. There were no significant differences among the subgroups for c-Myc, cyclin D1, MDM-2, Mcl-1, Bcl-2, CD56, p27, caspase 3, or survivin expression. In conclusion, among these 59 IMTs, ALK reactivity was associated with local recurrence, but not distant metastasis, which was confined to ALK-negative lesions. Absent ALK expression was associated with a higher age overall, subtle histologic differences, and death from disease or distant metastases (in a younger subset). Other proliferative, apoptotic, and prognostic markers did not correlate well with morphology or outcome. Thus, ALK reactivity may be a favorable prognostic indicator in IMT and abdominopelvic IMTs recur more frequently.     

Sporadic cutaneous angiosarcomas: a proposal for risk stratification based on 69 cases

Angiosarcomas have traditionally been considered high-grade lesions for which histologic features and grading have played no role in prognostication and, consequently, they have been excluded from the American Joint Committee on Cancer staging system. We have, therefore, analyzed 69 cutaneous angiosarcomas seen in consultation and not associated with lymphedema or prior radiation therapy to determine if a combination of histologic and clinical parameters could be used to differentiate indolent from aggressive tumors. The clinical features analyzed included patient age, location, size, depth, and focality of the lesion; the histologic features studied included pattern of growth (vasoformative vs. solid), nuclear grade (high vs. low), necrosis (present/absent), cell type (epithelioid or spindled), extent of inflammatory infiltrate (minimal vs. marked), and mitotic rate. Lesions occurred on the head/neck (49), extremities (15), and trunk (5) of adults (21 to 94 y) and predominated in males (41 males; 28 females). Tumors ranged in size from 0.3 to 15 cm (average 3.1 cm) and involved the papillary (n=9), reticular (n=16), or deep dermis/ subcutis (n=30). They could be predominantly vasoformative (n=28) to solid (greater than 50% solid, n=41). Most lesions were of high (n=65) as opposed to low (n=4) nuclear grade, were mitotically active (0 to 99/10 high power fields), and occasionally displayed necrosis (n=14) and epithelioid features (n=21). Inflammatory infiltrates were minimal in most cases. Follow-up information was obtained for all patients. Recurrences developed in 18 patients (26%) and metastasis in 15 (22%) to the following sites: lung (6), lymph node (7), liver (2), bone (2), and parotid gland (1). Forty-seven patients died (30 of disease) and 22 were alive at last known follow-up (range, 16 to 158 mo; mean, 65; median, 36). Five-year disease-specific survival was 48%. By univariate analysis only older age, anatomic site, necrosis, and epithelioid features correlated with increased mortality. Tumors were stratified into low (n=41) or high (n=28) risk groups based on necrosis and/or epithelioid features. By multivariable analysis, high-risk group (hazard ratio 4.07, P=0.0004) and age >70 (hazard ratio 2.79, P=0.012) were associated with increased mortality, and tumor depth (P=0.048) correlated with the risk of local recurrence. The high-risk group had a significantly worse prognosis than the low-risk group with 3-year survival of 24% and 77%, respectively. No patients with high-risk features survived 5 years. In conclusion, we report that a combination of clinical and histologic features allows stratification of angiosarcoma patients into 2 risk groups that are strongly associated with marked differences in clinical course. These features seem to diminish in importance with increased tumor size and are probably most useful in tumors less than 5 cm in maximum dimension.     

Liposarcomas of the mediastinum and thorax: a clinicopathologic and molecular cytogenetic study of 24 cases, emphasizing unusual and diverse histologic features

Liposarcoma rarely occurs in the mediastinum, and most reports predate the current genetically based classification system. We report the clinicopathologic and molecular genetic features of a series of thoracic liposarcomas identified over a 60-year period. Twenty-four confirmed cases were reclassified using the most recent World Health Organization classification. Fluorescent in situ hybridization for CPM amplification and/or DDIT3 rearrangement was performed on selected cases. The 24 cases occurred in 13 men and 11 women (mean age, 53 y; range, 15 to 73 y) and arose in all mediastinal compartments. All subtypes were encountered with 8 well-differentiated liposarcomas, 6 dedifferentiated liposarcomas (3 of 6 confirmed CPM+), 7 pleomorphic liposarcomas (2 of 7 confirmed CPM-, 1 of 7 confirmed DDIT3-), 2 myxoid liposarcomas, and 1 unclassifiable liposarcoma (CPM- and DDIT3-). Unusual histologic features included myxoid well-differentiated liposarcoma mimicking myxoid liposarcoma (2 cases), lipoleiomyosarcoma (1 case), dedifferentiated liposarcoma with "meningothelial"-like dedifferentiation, differentiated myxoid liposarcoma mimicking well-differentiated liposarcoma (CPM-), and pleomorphic liposarcoma with epithelioid and myxoid change. Follow-up information was available for 19 patients (mean, 55 mo; range, 8 to 252 mo). Outcome was strongly associated with histologic subtype, with death from disease occurring in 1 of 6 well-differentiated, 1 of 4 dedifferentiated, 5 of 7 pleomorphic, and 2 of 2 myxoid liposarcomas. The mediastinum shows a preponderance of uncommon subtypes and unusual morphologic variants. Correct classification has important implications, with most patients with well-differentiated/dedifferentiated liposarcoma having a protracted clinical course, in contrast to the more rapid disease progression seen in patients with myxoid and pleomorphic liposarcoma.