Hepatocellular carcinoma associated with extrahepatic primary malignant neoplasms

Background We studied hepatocellular carcinoma (HCC) with extrahepatic primary malignant neoplasms (EPMNs) and investigated its clinical and pathologic relevance. Method Data from autopsies performed during the last 10 years (January 1985 to December 1994) on 146 patients with HCC were analyzed at Maebashi Red Cross Hospital. The 146 patients consisted of 116 men and 30 women ranging in age from 38 to 87 years at the time of death. Results EPMNs were found in 21 patients: in the large bowel (6 cases), stomach (4 cases), thyroid (2 cases), urinary bladder (2 cases), small intestine (2 case), liver (1 case) and 1 case in the lung, pancreas, prostate, and breast, respectively. One patient had a malignant lymphoma in the small intestine. Ten EPMNs (47.6%) were latent or found at autopsy. The frequency of blood transfusion was significantly higher in the patients with EPMNs than in those without EPMNs. Those with EPMNs tended to be older and more likely to be male. Sixteen of the 21 patients died of liver-related causes. Two patients died of a second cancer, and 3 died of reasons other than malignancy, such as brain hemorrhage and pneumonia. Conclusion Fully 14.4% of patients whose autopsies showed HCC had EPMNs. Survival from the time of diagnosis of HCC did not differ significantly in the patients with EPMNs. These observations suggest that EPMNs did not change the prognosis of these patients with HCC, even when their EPMNs had been detected and treated early.     

Latent malignancies at autopsy: a little used source of information on cancer biology.

Latent carcinomas, found incidentally at autopsy, are defined, and information about such tumours in the prostate, adrenal gland, kidney and thyroid is reviewed. A previously unsuspected carcinoma of the prostate was found in 350 of 1327 (26.4%) autopsies performed in seven countries on men over 45 years of age. The prevalence of latent carcinoma of the prostate at autopsy was greater in older men and in areas of higher incidence and/or mortality, as for clinical carcinomas. Neuroblastomas of the adrenal gland have been reported at a rate of 1:39 in newborn infants who died of other causes; this rate is comparable to that of latent prostatic carcinoma. Neuroblastomas are not found in the adrenal glands of infants older than three months, indicating that the body has a method for destroying them. Latent carcinomas are also found in the thyroid gland at autopsy, at rates ranging from 10 to 30%. The age and area differences seen for prostatic carcinoma do not appear to be operative for these tumours; moreover, latent carcinomas are found more frequently in males, whereas the clinical disease is twice as frequent in females. More research should be carried out to elucidate the differences between people who develop clinical carcinoma, those who have a latent carcinoma 'under control' and those who have neither.     

The central nervous system in childhood leukemia. III. Mineralizing microangiopathy and dystrophic calcification.

We determined the prevalence, histopathologic features, and clinical correlations of a distinctive vascular lesion within the central nervous system (CNS) of children who died with acute lymphoblastic leukemia (ALL). Of 163 brains examined at autopsy, 28 (17%) had a noninflammatory mineralizing microangiopathy, usually accompanied by varying amounts of necrosis and calcification in adjacent neural tissue. The lesion always involved the lenticular nucleus with or without additional involvement of cerebral cortex. It was not the cause of death in any patient. An analysis of clinical features common to patients with microangiopathy indicated that cranial irradiation, in doses as low as 1500 rad, had induced the degenerative process. Survival beyond 10 months from the time of irradiation and multiple postirradiation CNS leukemic relapses, both had significant influences on the development of the lesion. Chemotherapy, particularly systemic or intrathecal methotrexate, might have contributed to the disease process, but apparently was not the instigating factor. Patients at greatest risk for developing microangiopathy are those under 10 years of age at the time of cranial irradiation, who then live more than 10 months and develop multiple CNS leukemic relapses.     

Long-term survival in patients with supratentorial glioblastoma

The authors report 11 patients with cerebral glioblastoma who lived at least 5 years after their initial diagnosis. There were 6 female and 5 male; the mean age was 39 years (range 24–55 years). All patients were treated surgically and postoperatively received whole-brain radiotherapy and chemotherapy. Five patients (45%) presented local recurrences after an average interval of 3.9 years from treatment. At average follow-up of 9 years (range 5–14 years), 7 patients (64%) were alive after an average interval of 8.1 years; 4 patients (36%) died from local relapse. Survival was influenced by patient age and, to a lesser degree, by treatment. A review of the literature, together with our own series, suggest that death from recurrence disease is unusual in glioblastoma patients who survive more than 5 years.     

Metastatic pattern in non-resectable non-small cell lung cancer

This study describes the metastatic pattern at autopsy in patients with non-resectable non-small cell lung cancer (NSCLC) and evaluates the impact of various pretreatment variables and treatment outcomes on the metastatic spread. In eight phase II chemotherapy trials from 1985 through 1993, 337 patients were treated and 51 autopsies were performed (autopsy rate 15%). The male/female ratio was 31/20, median age 56 years (range 36-71), response rate to chemotherapy 8%, and median survival 88 days (range 3-899). Histologic types included adenocarcinoma, 31 cases (60%), squamous cell carcinoma, 9 cases (18%), large cell carcinoma, 9 cases (18%), and unclassified NSCLC, 2 cases (4%). Patients who were autopsied had a shorter median survival than patients without autopsy (p = 0.002, log-rank test). Most commonly involved metastatic sites found at autopsy were mediastinal lymph nodes (84%), pleura (51%), liver (47%), bone (34%), brain (32%), pericardium (29%), adrenals (29%). The median number of involved organs was 5 (range 1-16), with a median of 3 intrathoracic sites (range 1-8) and 2 extrathoracic sites (range 0-11). Patients who initially had metastatic NSCLC also had significantly more metastatic sites at autopsy both extrathoracic (p = 0.004) and totally (p = 0.03) compared to patients with locally advanced disease. No other relation to pretreatment variables was found.     

Correlation of clinical diagnosis with autopsy findings.

We investigated 110 cases, selected at random out of the total of 1876 autopsies performed in the Institute of Pathological Anatomy and Histology at the University of Ferrara-Arcispedale Santa Anna on patients who had died at the hospital during 1983-87. Clinical data were taken from 'necropsy request forms' filled in by clinicians and from medical records. We then evaluated the extent of agreement and disagreement, expressed as underdiagnosis (false-negative) and overdiagnosis (false-positive), between the clinical and pathological records with regard to primary disease and to cause of death. Agreement between the diagnoses was 81% for primary disease and 58% for cause of death. The diagnoses of neoplastic, cerebrovascular and cardiovascular diseases showed the closest agreement. Among the neoplasms, those of the liver, gall-bladder, pancreas, retroperitoneal space and prostate were most often overlooked in clinical diagnoses. We had conflicting results for cancer of the lung and of the colon-rectum, for which there was a high level of agreement, but also a large number of false-positive cases and cases in which they were found by chance at autopsy. For cerebrovascular diseases, false-negative and false-positive diagnoses were seen most often for cause of death. With regard to cardiovascular diseases, a relatively uniform distribution was found for myocardial infarction among the three categories, and a high rate of agreement was found for pulmonary embolism. Of all diseases, bronchopneumonia was associated with the highest percentage of false-negative diagnoses for cause of death. Our data on digestive diseases show the strongest agreement on diagnosis of primary disease in relation to cirrhosis of the liver; a high rate of agreement on cause of death was confirmed for alimentary bleeding. Active tuberculosis was detected only at autopsy. We conclude that autopsy is a valid tool for investigation, despite the availability of sophisticated diagnostic techniques.     

Malignant fibrous histiocytoma of jaws. A clinicopathologic study of 11 cases

Malignant fibrous histiocytoma (MFH) of the jaws is a highly malignant tumor that recurs, metastasizes, and usually causes death despite aggressive surgical therapy. This clinicopathologic review looks at five patients with MFH of the maxilla and six with MFH of the mandible. Five male and six female patients ranged in age from 12 to 75 years (mean, 35.4 years). All patients had large lytic areas of bone destruction, often with soft tissue extension. Two cases were postirradiation sarcomas, one of the maxilla and the other of the mandible. All patients underwent surgery and eight patients received chemotherapy when disease recurred locally or metastasized. Seven patients had local recurrences 3 to 13 months following surgery, and six patients had distant metastases. Of the 11 patients, 7 died of their disease, 1 died of unknown causes, and another with extensive local disease was lost to follow-up after 1.7 years. Two patients with recurrent disease are alive at 18 and 27 months postoperatively.     

Ascending myelitis after intensive chemotherapy and radiation therapy in children with cranial parameningeal sarcoma.

In 1977, a program of early, wide-field radiation therapy (RT) to the central nervous system and repeated lumbar intrathecal (IT) medications along with systemic chemotherapy was begun by the Intergroup Rhabdomyosarcoma Study (IRS) for patients younger than 21 years of age with cranial parameningeal sarcoma and a high risk of meningeal extension. From 1977 until 1987, 149 eligible patients with high-risk cranial parameningeal sarcoma were enrolled in IRS trials. None had evidence of lower extremity or sphincter impairment at diagnosis. Five of the 149 (3.4%) had ascending myelitis at 5.5 to 9 months after the initiation of therapy, with loss of sphincter control and inability to walk; this progressed to severe flaccid quadriparesis and necessitated long-term ventilatory support in 4. All five had received vincristine, dactinomycin, cyclophosphamide, and doxorubicin; four also had received cisplatin and three also had received etoposide. All patients received 4770 to 5500 cGy to the primary tumor, and four patients received 3000 cGy of cranial RT. Three patients received cervical RT and two received spinal RT. The patients also received four to seven courses of IT methotrexate, hydrocortisone, and cytosine arabinoside. Three patients died: one after local tumor recurrence with central nervous system extension and two without known recurrence. In one of the latter patients, the results of an autopsy showed necrosis of the cervical spinal cord and caudal medulla. Although the exact cause of this complication is unclear, no additional cases have been reported to the IRS since the protocol was revised in 1987 to reduce the doses of the IT drugs and to limit them to four courses each.     

Papillary meningioma. Clinicopathologic study of seven cases and review of the literature

Seven cases of papillary meningioma are reported. The patients, 3 females and 4 males, were aged between 21 and 69 years. Five tumors were supratentorial, 1 was located in the left temporal bone, and 1 in the thoracic spinal canal. Five patients had local recurrences and died within 1.4 to 9 years of the original operation. In Case 2, one small pulmonary metastatic nodule was found at autopsy. Microscopically, these meningiomas showed foci of necrosis, numerous mitotic figures and local invasiveness. Psammoma bodies were occasional or absent. Forty-six papillary meningiomas have been identified in the literature. Certain histologic features (necrosis, high mitotic index, rich peripapillary reticulin network) and evolutive events (high rate of local recurrence, development of distant metastases) suggest that this aggressive variant of meningioma could form a histologic link between syncytial, fibroblastic, and hemangiopericytic meningiomas.     

Metastatic carcinoma. The lung as the site for the clinically undiagnosed primary

Of 387 patients who died with lung cancer, 28 cases were reviewed (7.2%) which were clinically undiagnosed. The male:female ratio was 3.6 and mean age was 64 years in the males, 47 years in the females. The most frequent presenting symptoms were neurologic. Prior to death, 21 patients had known or suspected metastatic disease (biopsy-proven in 12), while a malignant diagnosis was not considered in seven patients. Mean survival was 3.5 months. Despite a mean tumor size of 2.8 cm, most of the chest x-rays were not diagnostic even in retrospect. At autopsy, 65% of the tumors were adenocarcinomas (compared to 32% in the other 359 patients); 53% of these showed vascular and lymphatic invasion around the primary tumor, explaining their wide dissemination. In patients with small cell carcinomas (25% of the cases reviewed) or with solitary metastases (14% of the cases reviewed) therapeutic intervention could possibly have been beneficial.     

Obduktionen in der Onkologie

In oncology as well as in other fields of medicine autopsies play an important role as an instrument of quality management. There are numerous situations in which autopsies may disclose unknown antemortem findings in cancer patients. Autopsies of patients who have died in different phases of the cancer disease may bring valuable information about the individual cancer cases. The spectrum of autopsy indications varies from the confirmation of a clinically suspected cancer to the recognition of the final tumor stage or findings of therapy-related side effects or secondary diseases, such as unexpected infections. Several examples are provided to show unexpected results from the autopsies of cancer patients. In a 10-year analysis of 1,301 autopsy cases revealing malignant diseases 74.5% were clinically known and 20.2% (263 cases) were clinically unknown.     

Characteristics of chromate workers' cancers, chromium lung deposition and precancerous bronchial lesions: an autopsy study.

The characteristics of lung cancers induced by inhaled chromate were studied in 13 consecutive autopsies on male ex-chromate workers. In addition to histopathology, we examined: (1) the relationship between the occurrence of lung cancer and the amount of chromium (Cr) deposited in the lung as determined by atomic absorptiometry and (2) the chronological changes in five precancerous lung lesions followed by bronchoscopy till death. Twenty-one cancers were identified, including 16 lung tumours observed either during follow-up or at autopsy. Of these 16 tumours, 13 were found in six subjects, implying a high frequency of multiple cancers. Eleven (69%) out of the 16 tumours were of squamous cell type (including carcinoma in situ), this being twice as frequent as in age-matched controls. A further characteristic was predominance in the central part of lung (69%). The lung Cr burden was very much higher [40-15,800 micrograms g-1 (dry)] in patients with lung tumours than in those without (8-28 micrograms g-1). Five of the precancerous lesions followed by bronchoscopy originated at bronchial bifurcations. Four of these cases showed a return to normal histology at autopsy even without therapy, and the other did not progress.     

Underdiagnosis of carcinoma of the stomach in the elderly: a 25-year autopsy study

Gastric carcinoma may present atypically in the elderly. Between 1955 and 1979, 571 autopsies on gastric carcinoma cases were carried out at the Gade Institute, Bergen. In 165 of them the diagnosis had not been made clinically. The latter patients were, on average, 10 years older at death than those in whom the diagnosis was made premortem, and their tumours were smaller. In 45 the tumour was considered an incidental autopsy finding, while 58 were diagnosed clinically as advanced cancer of unknown origin. In the remaining 62 cases the cancer was the underlying cause of death. Recognition of an elderly sub-group of patients whose gastric carcinomas presented atypically brings with it an increasing diagnostic challenge in our ageing population.     

Fatal infection in patients treated for small cell lung cancer in the Institute of Tuberculosis and Chest Diseases in the years 1980-1994

The study was performed to explore the frequency of infections present at death and infection as the main cause of death (fatal infection - FI) in 845 consecutive patients (pts) treated for small cell lung cancer (SCLC) at the Institute of Tuberculosis and Chest Diseases in Warsaw, in the period 1980-1994. Diagnosis of infection was based on clinical signs and symptoms, the presence of new lesions on the chest X-ray, microbiological tests and/or autopsy examination. All cases of fungal infection, Pneumocystis carinii pneumonia (PCP) and tuberculosis were proved by autopsy and microscopic examination (including special staining). FI was diagnosed if no progression of cancer was noted and no other complications occurred. Infection was present at the time of death in 116 patients (13.7%) and FI was the cause of death in 39 of them (4.6%). Nine patients died from fungal infection, eight from bacterial infection, seven from PCP and two from tuberculosis. In 13 cases the aetiology of infection found at autopsy was not determined. All FI patients received chemotherapy and corticosteroids, 16 of them also had radiotherapy on the tumour and mediastinum. Thirty-two out of 35 patients had leucopenia. The risk of death from infection was greater in patients above 60 years of age. Patients in bad performance status died of infection significantly earlier than others (P<0.05).     

Mucinous carcinoma of the ovary. Pathologic prognostic factors.

Thirty-four ovarian mucinous carcinomas defined by nuclear stratification in excess of three layers (noninvasive mucinous carcinoma, NIMC) or stromal invasion (invasive mucinous carcinoma, IMC) were examined to define prognostic indicators. Twenty-two patients had NIMC (Stage I, 15; Stage II, 1; Stage III, 5; and Stage IV, 1). Twelve patients had IMC (Stage I, one; Stage II, one; and Stage III, ten). Fifteen patients died, ten with IMC and five with NIMC (mean survival, 16.7 months). Nineteen patients survived, two with IMC and 17 with NIMC (mean follow-up, 12 years). Ten of the 12 patients with IMC who died had Stage III disease. Five of the 22 patients with NIMC who died included four with Stage III and one with Stage I disease. Among patients who died, those with IMC tended to have a shorter mean survival than those with NIMC. No differences among groups were identified with respect to nuclear grade, mitotic activity, percentage of tumor displaying more than three cell layers, or amount of invasion. In ovarian mucinous carcinoma, clinical stage and stromal invasion are the most important prognostic variables, and they are interrelated. Stage I NIMC rarely pursues an aggressive course.     

Primary female urethral carcinoma. A retrospective comparison of different treatment techniques

Between July 1951 and January 1984, 14 female patients (11 black and three white; average age, 58 years) were treated for primary urethral carcinoma. Five patients had radical surgery, six received preoperative radiotherapy (2000 cGy in five fractions) followed by anterior exenteration, and three had definitive radiotherapy (external beam 4000 to 5000 cGy plus 2800 to 3000 cGy interstitial implant). The mean follow-up times were 5.6, 3.9, and 2 years, respectively. In the first two groups, two of 11 patients (18%) are alive and well with no evidence of disease. The rest died of local as well as distant disease. In the third group, two of three patients (67%) are alive and well with no evidence of disease. The third patient died of papillary adenocarcinoma of the uterus 30 months later with no evidence of the primary tumor.     

Craniofacial osseous and chondromatous sarcomas in British Columbia--a review of 34 cases

Head and neck sarcomas are very rare diseases. The aim of this study was to assess the prevalence and presentation of hard tissue sarcomas in the head and neck and jaws. A search of the British Columbia Tumor Registry identified 34 craniofacial hard tissue sarcomas (11 chondrosarcomas, 23 osteosarcomas) over a period of 29 years. A male predominance (1.8:1) and a mean age of 40.4 years at diagnosis were seen. Of the 23 patients with osteosarcoma, one-third survived for 5 years and 12 (52%) died within a mean of 20 months. Of the 11 patients with chondrosarcoma, 45% survived for 5 years and two (18%) of the patients died within a mean of 6 months. In nine of the osteosarcoma patients (39%) the jaws were involved, and in six of those cases (67%) there was mandibular involvement. Swelling was the first sign in all jaw patients, with a mean age of 41.1 years at diagnosis and a male predominance with a ratio of 8:1. Three of the eight male patients with osteosarcoma of the jaw (38%) died within a mean of less than 1 year. Improved prognosis is related to early recognition and diagnosis to allow for adequate surgical resection. The benefit of a combination of surgery with irradiation or chemotherapy continues to be investigated.     

CHOD/BVAM regimen plus radiotherapy in patients with primary CNS non-Hodgkin's lymphoma

PURPOSE: To assess the efficacy and toxicity, including long-term neurotoxicity, of combined therapy with the CHOD/BVAM regimen given before cranial radiotherapy in the treatment of primary CNS lymphoma (PCNSL). METHODS AND MATERIALS: Thirty-one consecutive patients with PCNSL were treated with one cycle of cyclophosphamide, doxorubicin, vincristine, and dexamethasone (CHOD) and two of carmustine (BCNU), vincristine, cytosine arabinoside, and methotrexate (BVAM), followed by cranial radiotherapy (45 Gy whole brain plus a 10-Gy boost for single lesions). The median age was 59 years (range 21-70) and 39% had poor performance status. The median follow-up of patients was 4.1 years (range 2.7-9.0). RESULTS: Twenty-one patients had no PCNSL at the end of treatment. The 5-year actuarial probability of survival was 31% (95% confidence interval [CI]: 11%-57%), with a median survival of 38 months. Patients < 60 years had a survival significantly longer than those > or = 60 years (4-year survival: 58% (95% CI: 34-82%) vs. 29% (95% CI: 5-53%), respectively; p = 0.04). Two patients died during chemotherapy from pulmonary embolism and bronchopneumonia, respectively, with no evidence of PCNSL at the autopsy. Dementia probably related to treatment occurred in 5 (62%) of the 8 patients 60 years and older, and 4 of them died without evidence of relapse of PCNSL. Dementia correlated with developing brain atrophy and leuco-encephalopathy on serial CT or MR scans. CONCLUSION: This regimen can be given with the planned dose intensity to patients aged less than 70 years, and produces better survival than that reported with radiotherapy alone; however, dementia occurs in the majority of patients aged 60 years of age or more.     

Aspergillus pericarditis: clinical and pathologic features in the immunocompromised patient

There has been a proliferation of infectious complications due to Aspergillus in patients receiving chemotherapy for cancer and transplantation; however, aspergillus pericarditis has been rarely described. Reported here are the clinical and pathologic findings of Aspergillus pericarditis in six immunocomprised patients who came to autopsy in the past 11 years. Five had leukemia, one had received a renal transplant. All had pulmonary aspergillosis. Two had clinically overt pericarditis leading to cardiac tamponade and death. Pulmonary aspergillosis preceded development of pericardial signs. Chest radiographs, serial electrocardiograms, and echocardiograms showed abnormality but were nonspecific. Pericardiocentesis was performed in one patient but proved nondiagnostic and yielded only transient hemodynamic improvement; postmortem Gram stain of the spun sediment of that pericardial fluid revealed branched hyphae. Although five patients received Amphotericin B, whether it entered the pericardial space is uncertain. Postmortem examination revealed extensive pericardial involvement by Aspergillus associated with effusions as large as 1000 ml Aspergillus penetrated the pericardium by rupture of myocardial abscesses and invasion from contiguous pulmonary foci into the pericardial space. A clinical diagnosis of Aspergillus pericarditis was never established, and at least two died of their pericardial disease. Aspergillus pericarditis is a lethal cardiac infection, which is likely to increase in frequency, and should be considered in the hemodynamically unstable immunocompromised patient, especially when signs of pericarditis or pulmonary aspergillosis are present.     

Primary plasma cell leukemia occuring in the young

Plasma Cell Leukemia (PCL) is a rare form of plasma cell dyscrasia. Plasma cell leukemia has two variants: the primary form presents de novo in patients with no previous history of multiple myeloma (MM); the secondary form consists of a leukemic transformation in a previously recognized MM. In contrast to myeloma, PCL has an aggressive course. Median age at presentation is usually above 50 years. Here we report a case of primary PCL presenting at age of 21 years, which is extremely rare. She was treated with combination chemotherapy (VAD). Although she had a good response initially, later the disease progressed and she died 6 months after the diagnosis.