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Contralateral breast cancer: molecular differentiation between metastasis and second primary cancer.

Previous cancer in one breast is a strong known risk factor for cancer in the contralateral breast. Differences in tumor histology and nuclear grading are applied to distinguish between a metastatic spread and a second primary cancer, although cancers of the breast often share the same histological features. Comparison of genetic alterations in paired tumors may provide the most reliable approach for discerning clonal relationships, hence uncovering the presence or absence of multiple primary cancers. We compared tumors from 33 patients with cancer in both breasts for mutations in the p53 gene. With this molecular approach, we were able to define the relationship within paired tumors in 13 patients. The paired tumors of two patients shared the same mutation, revealing the second lesion in one case as a contralateral metachronous lymph node metastasis appearing 29 months after first surgery, and in the other as a spread to the opposite breast. In 11 patients, mutations were either discordant or solely present in one of the lesions, confirming the diagnosis of bilateral breast cancer. Histopathological evaluation had failed to provide firm diagnosis in nine out of 11 instances on account of concordances in pathological parameters such as histological type and grading. In our study, we could show that bilateral breast malignancies most frequently represent two primary breast cancers. We could also demonstrate that contralateral breast cancer spread does occur. Standard pathological assessment allowed a firm diagnosis only in the presence of different histological types.

Adult↗

[Double primary malignant tumors involving a lung cancer].

Patients with multiple primary malignant tumors involving a primary lung cancer have been analyzed at our department in the Gunma University hospital. With reference to the lung cancer, three quarters of these patients were clinically in stages III or IV. The lung cancers were histologically classified into 26 epidermoid cancers, 14 adenocarcinomas, one large cell carcinoma, and one small cell carcinoma. Other primary cancers were 13 gastric cancers, 7 laryngeal cancers, 6 cervical cancers, 3 colon cancers, and other such cancers. Cases manifesting simultaneous cancers showing less than a one-year interval were 15 whereas 27 cases had double primary cancers with intervals of over one-year. Eleven patients had been given radiation therapy for their initial malignant tumor, but only two cases were considered to have incurred a radiation-induced lung cancer with a latent period of 5 and 12 years respectively.

Adult↗

Current issues in the management of advanced Hodgkin's disease.

During the past two decades, the standard drug regimen has been the MOPP program and its variants MVPP or ChlVPP. The search for less toxic chemotherapy in terms of decreased sterility and myelodysplasia-acute non-lymphocytic leukemia prompted the design of ABVD. Recent data from different countries indicate that adriamycin-based combinations as ABVD or MOPP alternating with ABVD appear very useful to improve treatment outcome compared to MOPP alone. The combination of chemotherapy and radiation has been utilized by many institutions in practically all stages of Hodgkin's disease. The intent is to optimize the cure rate and with the theory that less intensive therapy of both modalities may carry a lower risk of iatrogenic complications without compromising treatment outcome. In patients relapsing from curative radiotherapy, combination chemotherapy such as ABVD or MOPP/ABVD is recommended as the most effective salvage regimen, associated to further irradiation if technically feasible. In patients relapsing from primary chemotherapy, clinicians have first to take into consideration whether the duration of first complete remission is longer than 12 months. In this case, retreatment with the same drug regimen remains the treatment of choice. In patients with progressive lymphoma while on primary chemotherapy or showing remission duration lesser than 12 months, non-cross resistant chemotherapy or high dose therapy plus autologous bone marrow transplantation are indicated.

Antineoplastic Combined Chemotherapy Protocols↗

Second primary neoplasms in patients with retinoblastoma.

In a series of 882 retinoblastoma patients, 384 known to have the genetic form of the disease and 498 others, 30 patients developed second primary neoplasms. The spectrum of these second neoplasms is discussed in relation to the forms of treatment used for the retinoblastoma. Cumulative incidence rates of second tumours in the whole series are 2.0% at 12 years after diagnosis and 4.2% after 18 years. For patients with the genetic form of retinoblastoma the cumulative incidence rate after 18 years is 8.4% for all second neoplasms and 6.0% for osteosarcomas alone. The inherent risk among survivors from genetic retinoblastoma of developing an osteosarcoma, excluding all possible effects of treatment, is estimated to be 2.2% after 18 years. Within the field of radiation treatment the cumulative incidence rate for all second neoplasms after 18 years is 6.6% and for osteosarcomas alone 3.7%. There is some evidence that patients with genetic retinoblastoma are particularly sensitive to the carcinogenic effects of radiation. The results also suggest that the use of cyclophosphamide may increase the risk of second primary neoplasms in patients with genetic retinoblastoma. The incidence rates of second primary neoplasms in retinoblastoma survivors reported here are lower than those quoted for previously published series. Evidence from this and other papers strongly suggests an association between retinoblastoma and malignant melanoma.

Child, Preschool↗

Patients with multiple primary gastric cancers tend to develop second primaries in organs other than the stomach.

The multiple occurrence of a single cancer tends to result in the increased vulnerability of some other organs to another malignancy. In the present study, we examined a total of 1,606 patients with gastric cancer to ascertain whether the frequency of second primaries in organs other than the stomach is higher in patients with multiple gastric cancers than in those with a single gastric cancer. Primary cancers of other organs were present in 87 (5.9%) of 1,474 patients with single gastric cancer and in 16 (12.1%) of 132 patients with multiple gastric cancers. The difference was statistically significant. The most frequent site of the occurrence of a second primary was the colo-rectum, followed by the urogenital organs, uterus, breast, and lung in descending order of frequency. We therefore assume that the occurrence of multiple cancers in the stomach is not merely a chance phenomenon but is related to both genetic predisposition and environmental factors.

Adenocarcinoma↗

Risk factors for young premenopausal women with endometrial cancer.

OBJECTIVE: Endometrial cancer is the most common gynecologic malignancy in the United States. The mean age at diagnosis is 61 years; however, 5-30% of women are aged younger than 50 years at the time of diagnosis. The objective of this study was to conduct a clinical and pathologic review of endometrial cancers diagnosed in premenopausal women aged younger than 50 years, to better identify the risk factors for this subgroup of women. METHODS: We conducted a retrospective cohort study of patients with histologically confirmed endometrial cancer treated at the University of Texas, M. D. Anderson Cancer Center from 1989 to 2003. Clinical characteristics including age, body mass index (BMI), parity, diabetes, and personal or family history of cancer were obtained from the medical record. Pathologic information was obtained from pathology reports. RESULTS: Twelve percent (188/1531) of all patients with endometrial adenocarcinoma were aged younger than 50 years. The mean age at diagnosis was 41 years (range 21-49 years). Mean BMI was 34 kg/m(2) (range 18-68); 58% of patients had a BMI of 30 or greater. Fifty-five percent were nulliparous and 39% reported irregular menstrual cycles. The incidence of both diabetes and hypertension was 23%. Thirty-six patients (19%) had synchronous ovarian cancers. CONCLUSION: We found that the majority of patients diagnosed with endometrial cancer at a young age were obese and nulliparous. In addition, we found a high incidence of synchronous primary ovarian cancers in this cohort of young, premenopausal women.

Adenocarcinoma↗

Radiation-induced sarcoma of the breast in a female adolescent. Case report with histologic and therapeutic considerations.

A 14-year-old girl developed a radiation-induced sarcoma of the left breast after successful combined surgical and radiation therapy of a left adrenal carcinoma when she was 9 months old. The breast lesion was histologically described as a stromal sarcoma with fibrosarcomatous and myxosarcomatous areas. The second primary lesion and local recurrence of this was treated with surgery. At each recurrence the tumor became more aggressive both clinically and histologically, and eventually proved fatal.

Adolescent↗

[Primary hemorrhagic spindle cell tumor of the lymph node with amianthoid structures. Case report and review of the literature].

An example of a benign haemorrhagic spindle cell tumour of the lymph node (synonym: intranodal myofibroblastoma) is presented, which was first described 5 years ago and has not as yet been documented in the German literature. This rare benign mesenchymal neoplasm of the lymph node occurs almost exclusively in the inguinal region. Diagnostic criteria include its composition of myofibroblastic cells (with immunoreactivity for vimentin and actin), which may show nuclear palisading, the presence of peripheral haemorrhage zones and the occurrence of characteristic amianthoid structures, which have the ultrastructural appearance of dense meshworks of collagen fibers. Knowledge of this tumour entity is important for differential diagnosis of primary and secondary malignant mesenchymal neoplasias of the lymph node.

Actin Cytoskeleton↗

Subsequent cancer in patients with Ewing's sarcoma.

Among 31 long-term survivors of Ewing's sarcoma, two patients developed second primary cancers, compared to an expected number of 0.03 (relative risk = 72; 95% confidence limit = 8-259). One patient had renal medullary neuroblastoma, which is not known to be related to Ewing's tumor or its therapy. The second patient had a bone fibrosarcoma, arising at the primary tumor site, which was thought to be radiation-induced. The risk of radiation-induced bone sarcomas was lower, although not significantly so, than in a recently reported series of Ewing's tumor. These two reports suggest that patients with Ewing's sarcoma have a tendency to develop radiogenic sarcomas following primary megavoltage radiation therapy. The lowest radiation dose consistent with local tumor eradication should be employed to minimize the risk of subsequent radiogenic cancer.

Adolescent↗

Multiple primary melanomas: implications for screening and follow-up programs for melanoma.

BACKGROUND: Once individuals are diagnosed with malignant melanoma, they are at an increased risk of developing another melanoma when compared with the normal population. METHODS: To determine the impact of an intensive follow-up protocol on the stage of disease at diagnosis of subsequent primary melanomas, a retrospective query was performed of an electronic medical record database of 2,600 consecutively registered melanoma patients. RESULTS: Sixty-seven patients (2.6%) had another melanoma diagnosed at the time of presentation to the clinic or within 2 months (synchronous) and another 44 patients (1.7%) developed a second primary melanoma during the follow-up period (metachronous). For the 44 patients diagnosed with metachronous lesions, the Breslow mean tumor thickness for the first invasive melanoma was 2.27 mm compared with 0.90 mm for the second melanoma. The first melanomas diagnosed are thicker by an average of 3.8 mm (p = 0.008). The mean Clark level for the initial melanoma was greater than the mean level for subsequently diagnosed melanomas (p = 0.002). Twenty-three percent of the initial melanomas were ulcerated, whereas only one of the second primary lesions showed this adverse prognostic factor (p = 0.002). CONCLUSIONS: Once individuals are diagnosed with melanoma, they are in a high-risk population for having other primary site melanomas diagnosed and should be placed in an intensive follow-up protocol consisting of a complete skin examination.

Adult↗

Solitary pulmonary nodules in patients with extrapulmonary neoplasms.

PURPOSE: To determine the frequency of single lung metastasis, primary lung cancer, and benign lesions in patients with a solitary lung nodule and a primary extrapulmonary neoplasm. MATERIALS AND METHODS: The authors evaluated the electronic charts of 149 patients with an extrapulmonary malignant neoplasm and a solitary pulmonary nodule. The histologic characteristics of the nodule were correlated with those of the extrapulmonary neoplasm and with patient age and smoking history. RESULTS: Patients with carcinomas of the head and neck, bladder, breast, cervix, bile ducts, esophagus, ovary, prostate, or stomach were more likely to have primary bronchogenic carcinoma than lung metastasis (ratio, 25:3 for patients with head and neck cancers; 26:8 for patients with other types of cancer combined). Patients with carcinomas of the salivary glands, adrenal gland, colon, parotid gland, kidney, thyroid gland, thymus, or uterus had fairly even odds (ratio, 13:16). Patients with melanoma, sarcoma, or testicular carcinoma were more likely to have a solitary metastasis than a bronchogenic carcinoma (ratio, 23:9). Thirty patients had a benign nodule. There was substantial overlap in age distribution among the patients with benign disease, lung cancer, and metastasis, although no patient younger than 44 years had a lung cancer. Smokers had a 3.5-fold higher chance of developing lung cancer compared with nonsmokers. CONCLUSION: The likelihood of a primary lung cancer versus a metastasis depends on the histologic characteristics of the extrapulmonary neoplasm and the patient's smoking history.

Adult↗

Lung cancer. Special treatment issues.

This chapter of the Lung Cancer Guidelines addresses patients with particular forms of non-small cell lung cancer that require special considerations. This includes patients with Pancoast tumors, T4N0,1M0 tumors, satellite nodules in the same lobe, synchronous and metachronous multiple primary lung cancers (MPLC), and solitary metastases. For patients with a Pancoast tumor, a multimodality approach, involving chemoradiotherapy and surgical resection, appears optimal provided appropriate staging has been carried out. Patients with central T4 tumors that do not have mediastinal node involvement are uncommon. When carefully staged and selected, however, such patients appear to benefit from resection as part of the treatment as opposed to chemoradiotherapy alone. Patients with a satellite lesion in the same lobe as the primary tumor have a good prognosis and require no modification of the approach to evaluation and treatment from what would be dictated by the primary tumor alone. On the other hand, it is difficult to know how best to treat patients with a focus of the same type of cancer in a different lobe. Although MPLC do occur, the survival results after resection for either a synchronous presentation or a metachronous presentation with an interval of < 4 years between tumors are variable and generally poor, suggesting that many of these patients may have had a pulmonary metastasis rather than a second primary lung cancer. A thorough and careful evaluation of these patients is warranted to try to differentiate between patients with a metastasis and those with a second primary lung cancer, although criteria to distinguish them have not been defined. Finally, some patients with a solitary focus of metastatic disease in the brain or adrenal gland appear to benefit substantially from resection.

Adrenal Gland Neoplasms↗

Adenocarcinoma in the lung in patients with breast cancer. A prospective analysis of the discriminatory value of immunohistology.

In some patients with a history of breast cancer who also have masses in the lung, making a clinical distinction between primary pulmonary neoplasia and pulmonary metastasis of mammary carcinoma may be impossible. To ascertain whether immunohistologic studies could contribute to resolving this problem, the authors undertook a prospective study of 30 cases showing synchronous or metachronous adenocarcinomas in these two sites. A predefined panel of antibodies--as derived from published antigenic catalogs for breast and lung cancer--was applied to each case. Tumors were interpreted as metastases if they were positive for gross cystic disease fluid protein-15, estrogen receptor protein, or S-100 protein. Conversely, primary adenocarcinomas of the lung were defined by their expression of carcinoembryonic antigen and a lack of the other three determinants. Using these criteria, 15 lesions were classified as metastatic; 11 were categorized as primary pulmonary adenocarcinomas; and 4 cases were indeterminate in origin. Responses to corresponding therapeutic protocols generally supported the validity of the immunohistologic diagnoses; 8 of 15 patients treated for metastatic breast cancer were well at least contact, as were 5 of 11 patients who received therapy for primary carcinoma of the lung. These data suggest that immunohistology plays a useful role in distinguishing mammary from pulmonary adenocarcinomas.

Adenocarcinoma↗

Multiple primary malignant tumors in patients with head and neck cancer: results of a prospective study and future perspectives.

Multiple primary tumors are a known phenomenon in head and neck cancer. They are partially responsible for the limited improvement in survival of head and neck cancer during the past 20 years. Only a few prospective data have been published about the incidence of metachronous tumors. The authors prospectively studied 127 patients with squamous cell carcinoma of the head and neck. The overall incidence of second primary tumors was 13.5% (simultaneously, 3%; synchronously, 5.5%; and metachronously, 8%). More than 90% of the recurrences of the first primary tumor occurred within the first 2 years following primary treatment, but the second primary tumors continued to occur gradually in the course of follow-up. Most of the second primary tumors were discovered because the patients developed symptoms (14/17). Survival after detection of the second primary tumor was poor. The development of a second primary tumor was of equivalent prognosis to a recurrence of the primary tumor. Future directives include the development of more adequate screening methods. Identification of potential early markers for the development of a squamous cell carcinoma at the level of the mucosa at risk and in serum could be of value for the early detection of individuals at risk.

Carcinoma, Squamous Cell↗

Second malignant tumors after cancer in childhood.

Studies were made of the development of second malignant tumors in children treated at the Sidney Farber Cancer Institute. In 1973 a retrospective analysis identified second cancers in 15 of 410 patients who survived a childhood cancer. During the period 5-24 years after diagnosis of the first cancer, the cumulative probability of developing a new cancer was 12%. This frequency was approximately 20-fold higher than the expected rate for the general population. Prospective study of the series since 1973 has identified a second primary cancer in five additional patients. The majority of second cancers were in the field of prior radiotherapy, and were attributable to the oncogenic effect of radiation. Genetic susceptibility factors were identified in individual patients.

Adolescent↗

Multiple primary tumours in women following breast cancer, 1973-2000.

We investigated the predictors of the risk of developing a second primary cancer after breast cancer, this occurring in about 12% of affected women. The analysis included 335 191 females, registered in the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) database, who had been diagnosed with breast cancer. Observed numbers of subsequent cancers in the SEER database with a first breast cancer diagnosed from 1973 to 2000 were compared with the expected numbers based on age-adjusted incidence rates to calculate standardised incidence ratios. Kaplan-Meier curves were conducted to determine the median time until the second primary cancer diagnosis. Average number of years until diagnosis varied by site and by age as well as median years until second cancer diagnosis. Most cancer risks decreased with age, but there was an increase in aging-related cancers such as lung cancer. The median years of follow-up were well beyond the 5-year mark. Breast cancer survivors should be advised of their increased risk for developing certain cancers in their lifetime.

Adult↗

Multiple primary cancers in patients with gastric cancer.

BACKGROUND/AIMS: Some gastric cancer patients have multiple primary cancers (MPC). We evaluate the current status of MPC with gastric cancer. METHODOLOGY: 2,109 gastric cancer patients treated between 1987 and 2002 were analyzed. RESULTS: There were 99 MPC with gastric cancer (4.7%). Second cancer (77.8%) was discovered within 5 years before and after the onset of gastric cancer. 34.3% of patients were discovered within 1 year (synchronous tumor). In the 77 male patients, prostate cancer was the most common occurrence (19.5%), followed by cancers of the colon (18.2%) and liver (14.3%). In the 22 female patients, colon cancer was the most common (31.9%) followed by breast and cervix cancers (22.7%). These cancers were the most common diseases in Taiwan in the same period. Gastric cancer patients with MPC had less stromal reaction and better survival than those without. Patients with metachronous secondary tumors had more peritoneal dissemination and worse survival than those with synchronous primary cancer. CONCLUSIONS: Gastric cancer patients may develop second cancer(s), which is often a current prevalent malignancy. Knowledge of time to development and mode of organ association may allow clinicians to detect potentially curable subsequent cancer(s).

Age Factors↗