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Thyroid adenoma following treatment of acute lymphocytic leukemia.

Sequelae of the treatment of children with acute lymphocytic leukemia (ALL) include multiple effects on the endocrine system, especially as it relates to growth and puberty. Thyroid dysfunction, and in particular, the occurrence of thyroid neoplasia, has been only rarely described. We report the development of benign thyroid neoplasms in two patients 9 years following the diagnosis and treatment of ALL. Both patients were clinically and biochemically euthyroid with noncystic "cold" nodules found on thyroid scan. In light of these observations, and along with previous reports of malignant thyroid neoplasia in children with ALL, long-term careful observation of children successfully treated for ALL is indicated.

Adenoma↗

Secondary acute myelogenous leukemia in patients previously treated for childhood renal tumors: a report from the National Wilms Tumor Study Group.

PURPOSE: This review characterized cases of secondary acute myelogenous leukemia (AML) occurring after treatment of renal neoplasms on protocols of the National Wilms Tumor Study Group (NWTSG) between October 1969 and December 1991. PATIENTS AND METHODS: The NWTSG database was reviewed for cases of secondary AML and for WT1 status of the affected patients. Referring institutions were contacted by a confidential letter requesting pathology reports, results of immunophenotyping, cytogenetic, and molecular analyses, and details concerning treatment of AML. RESULTS: Of the 5,278 patients treated during the study period, 43 had second malignant neoplasms, and 7 of these 43 had AML. At the time of diagnosis of Wilms tumor, the median age of the seven patients (4 boys) was 3.2 years. Five of the seven renal neoplasms had favorable histologic characteristics. The most common French-American-British morphology was M5. One patient had bilateral tumors, and two were treated for recurrent Wilms tumor. All patients received chemotherapy regimens that included doxorubicin (6) or etoposide (1), and six were treated with infradiaphragmatic irradiation. The median latency period from initial diagnosis of the renal neoplasm to development of secondary AML was 3 years (range, 1.2-4 yrs). One patient had the translocation t(9:11)(p22;q23); WT1 status was not noted for any of the seven patients. CONCLUSIONS: The development of secondary AML in this subset of patients after treatment of renal neoplasms may reflect the interaction of the effects of treatment and possible genetic predisposition toward cancer.

Abnormalities, Multiple↗

Angiosarcoma of the breast occurring soon after lumpectomy and breast irradiation for infiltrating ductal carcinoma: a case report.

Angiosarcoma of the breast is a rare second malignancy after breast irradiation for carcinoma. As with most radiotherapy-associated malignancies, the usual latent period after radiotherapy is many years. The authors present a case of angiosarcoma appearing in the breast 14 months after breast irradiation after lumpectomy and axillary node dissection for infiltrating ductal carcinoma.

Breast Neoplasms↗

Histology and clinical outcomes in patients with bilateral testicular germ cell tumors: the Memorial Sloan Kettering Cancer Center experience 1950 to 2001.

PURPOSE: The optimal management of bilateral testicular tumors continues to evolve. We examined the incidence, characteristics, histology, treatment and clinical outcomes of patients with bilateral testicular cancer. MATERIALS AND METHODS: Between 1950 and 2001, 3,984 patients with testicular cancer were treated at our center. A total of 58 patients with bilateral testicular germ cell tumors were identified. The clinical records of these 58 patients were reviewed for age, histology of the 2 tumors, stage at presentation of the first and second tumor, interval between tumors, treatment and clinical outcome. Median followup was 60 months. RESULTS: Ten of the 58 patients (17%) had synchronous tumors, while the other 48 (83%) had metachronous tumors with a median interval between tumors of 50.5 months. Overall seminoma was the most common histology of the synchronous and metachronous tumors. Most patients in the synchronous and metachronous tumor groups presented with low stage disease. Of the 58 patients 52 (89%) had no evidence of disease and 6 (11%) were dead of disease at the last followup. Treatment of the second tumor appeared to be influenced by therapy for the first tumor in 16.7% of cases. CONCLUSIONS: Patients with a history of testicular germ cell tumor require careful long-term monitoring of the contralateral testicle due to the risk of bilateral disease and potentially long latent period between the first and second tumors. Overall the clinical outcome is good in these patients when they are treated appropriately for histology and stage. In patients with metachronous tumors treatment of the contralateral tumor is rarely altered by prior treatment of the initial tumor.

Adult↗

Multifocal transitional cell carcinoma of the bladder and upper urinary tract: molecular screening of clonal origin by characterizing CD44 alternative splicing patterns.

PURPOSE: CD44 is a widely expressed cell surface adhesion molecule in which various isoforms arise from alternative RNA splicing mechanism during cancer initiation. We assessed whether multifocal transitional cell carcinoma of the urothelium is due to field change and/or intraluminal seeding and implantation. MATERIALS AND METHODS: In a series of 24 patients with synchronous and/or metachronous multiple urothelial cancers we performed reverse transcription-polymerase chain reaction analysis using a set of primers capable of amplifying all CD44 splice variant isoforms. After polymerase chain reaction products were electrophoresed band intensities with areas corresponding to the major isoforms (that is CD44s, CD44v10 and CD44v8-10) were quantified, and CD44v10-to-CD44s and CD44v8-10-to-CD44s ratios were calculated. Moreover, p53 gene mutations in exons 4 to 11 were screened by direct DNA sequencing. RESULTS: Of these 24 cases 18 showed similar CD44v10-to-CD44s and CD44v8-10-to-CD44s ratios in among multiple urothelial cancers in each case. However, in the remaining 6 cases these ratios were quite different among multiple cancer lesions. Furthermore, different types of p53 mutation were detected among multiple cancer lesions in only 2 of 24 cases, which also indicated different patterns of CD44 alternative splicing. CONCLUSIONS: These findings suggest that at least some multiple transitional cell carcinomas of the urothelium seem to be of independent origin based on the analysis of alternative RNA splicing of CD44. Moreover, this hypothesis was further supported by the evaluation of p53 gene mutation.

Alternative Splicing↗

Sarcomatoid carcinoma of the prostate: a study of 42 cases.

UNLABELLED: Sarcomatoid carcinoma of the prostate is a rare type of prostatic cancer. With the exception of 1 study, the morphologic features and patient outcomes have been reported only in relatively small case series and individual reports. We examined transurethral resection, needle biopsy, and radical prostatectomy specimens from 42 patients with sarcomatoid carcinoma of the prostate, all of which were received in consultation. Clinical information on 32 patients was obtainable. Five patients were lost to follow-up and information on the 5 remaining patients could not be obtained. Prior prostatic adenocarcinoma: The majority of patients (n=21; 66%) had a prior history of acinar adenocarcinoma of the prostate. Of the 14 men with available data, reported Gleason scores were 6 (n=7), 8 (n=4), and 10 (n=3). Of the remaining patients for whom this information was known, 11 patients presented with de novo sarcomatoid carcinoma. The time between the original diagnosis of acinar adenocarcinoma and diagnosis of sarcomatoid carcinoma ranged from 6 months to 16 years (mean 6.8 y). Concurrent adenocarcinoma: The majority of patients demonstrated a concurrent high grade acinar carcinoma of Gleason score 7 (n=3), 8 (n=9), 9 (n=10), and 10 (n=10). A subset of patients contained an admixed ductal adenocarcinoma (n=4), small cell carcinoma (n=3), squamous cell carcinoma (n=3), or other unusual pattern of prostate carcinoma (n=3). In 1 case, the diagnosis was based on immunohistochemical evidence of epithelial differentiation along with the history of prior adenocarcinoma. Morphology of the sarcomatoid component: The percentage of sarcomatoid growth ranged from 5% to 99% (mean 65%). Bizarre atypia with giant cells was present in 55% of cases. Admixed heterologous elements were identified in 10 cases (29%), including osteosarcomatous (n=7), chondrosarcomatous (n=5), and rhabdomyosarcomatous (n=2) elements. Of the 12 cases with received immunostains of the sarcomatoid component, 5/7 cases were at least focally positive for cytokeratin, 1/1 case was focally positive for Cam5.2, and 3/6 cases were focally positive for prostate acid phosphatase. The sarcomatoid component did not demonstrate immunoreactivity for prostate-specific antigen in 8 cases. PROGNOSIS: approximately half of all patients developed metastatic disease either at time of presentation or subsequently. Of patients with meaningful follow-up, 6/7 died within 1 year of the diagnosis of sarcomatoid carcinoma; 20 were alive yet with very short follow-up (median 1 y; mean 2.3 y). Kaplan-Meier analysis revealed that the actuarial risk of death at 1 year after diagnosis of sarcomatoid carcinoma was 20%. No correlation was identified between patient survival and morphologic features, before radiation or hormone therapy, or concurrent high-grade prostate cancer. Sarcomatoid carcinoma demonstrates diverse spindle and epithelial cell morphologies. The sarcomatoid component often has heterologous elements and, in 1 case, no epithelial component was seen on hematoxylin and eosin-stained sections. The epithelial component is typically high-grade acinar adenocarcinoma, yet other aggressive tumor subtypes such as ductal adenocarcinoma and small cell carcinoma may also be seen. Sarcomatoid carcinoma is an aggressive form of prostate cancer, the prognosis of which is dismal regardless of other histologic or clinical findings.

Aged↗

Malignant tumours in patients with a history of multiple laryngeal papillomas: the significance of irradiation.

For a period of more than 30 years irradiation was used in the treatment of multiple laryngeal papillomas, especially in children. The treatment was discontinued because a number of irradiated patients developed laryngeal carcinomas. There are however a number of reports of laryngeal and even bronchial carcinomas arising in patients with laryngeal papillomas who had not been irradiated. In addition, HPV type 11 has recently been found in laryngeal papillomas as well as in laryngeal and bronchial carcinomas, subsequently arising in the same patients, both irradiated and non-irradiated. The analysis of a series of 113 patients with laryngeal papillomas has shown that irradiated patients have a 16-fold increased risk of a subsequent carcinoma in the respiratory system.

Adolescent↗

Angiosarcoma in irradiated post-mastectomy chest wall.

A 61-year-old woman developed an angiosarcoma in the irradiated chest wall 2 1/2 and 4 years after mastectomy for a carcinoma of breast. The two sets of tumours were morphologically distinct and differed immunohistochemically. The short interval between post-operative irradiation and presentation of the angiosarcoma is unusual. The case is discussed in relation to others of allied type.

Breast Neoplasms↗

Basal cell carcinoma and breast carcinoma following repeated fluoroscopic examinations of the chest.

A 69-year-old white Italian woman was first seen at Memorial Sloan-Kettering Cancer Center in 1981 concerning several skin growths on her back. The patient had had several basal cell carcinomas surgically removed from her back during the preceding 5 years. There was no history of arsenic ingestion or prolonged sun exposure and her family history was negative for skin cancer. The patient had developed pulmonary tuberculosis in 1938 and was treated with pneumothorax therapy. She had had more than 50 fluoroscopic examinations of the chest following this therapy, as well as multiple diagnostic x-ray films since that time. She recalled that she had faced the fluoroscopy beam during the procedure. In 1959, she had a transabdominal hysterectomy for fibroid tumors. In 1980 she underwent a right modified radical mastectomy for adenoid cystic carcinoma of the breast; biopsies of lymph nodes were negative. Physical examination revealed a thin, white woman with a right mastectomy scar. On the back, clustered in the interscapular region, were multiple scars and nine erythematous nodules with pearly borders, telangiectasia, and translucent surfaces. Within several nodules there were areas of light and dark brown pigmentation. There were no other suspicious lesions on the head, chest, or extremities, nor did the patient show any evidence of the basal cell nevus syndrome. Biopsy of all lesions revealed basal cell carcinoma, some of which were pigmented, without evidence of chronic radiodermatitis. All lesions were treated with curettage and electrodesiccation three times with good cosmetic results (Fig. 1).

Breast Neoplasms↗

Point mutations in the c-K-ras 2 gene in multiple colorectal carcinomas.

The c-K-ras 2 gene mutations were examined in colorectal tumours from patients with synchronous or metachronous tumours in order to investigate tumorigenesis. Sixty-seven colorectal carcinomas from patients with a single lesion, 50 from patients with synchronous lesions, and 12 from patients with metachronous lesions were analysed for the presence of point mutations in codons 12 and 13 of c-K-ras proto-oncogene. In the patients with metachronous or synchronous lesions, the finding of the mutation in one tumour was not associated with a greater frequency of the mutation in other carcinomas from the same patient. In the patients with tumours that each contained the mutation, the mutations were not always the same. In tumours from the patients with original and synchronous lesions, the mutation frequency was significantly lower in advanced carcinomas invading through the entire muscularis propria (10.5%) than in early carcinomas confined to the mucosa (47.8%), and the mutation frequency in carcinomas invading through the entire muscularis propria was significantly lower in patients with synchronous lesions (10.5%) than in patients with a single lesion (37.7%). These results suggest that the tumorigenesis of colorectal carcinomas from patients with synchronous lesions is different from that in patients with a single lesion.

Adult↗

Adenocarcinoma arising from mature cystic teratoma of the ovary.

An extremely rare adenocarcinoma arising from a mature cystic teratoma is reported. A 58-year-old woman underwent bilateral salpingo-oophorectomy because of a tumor in each ovary. The right ovarian tumor (solid, 9.6 x 9.6 x 6.3 cm) was a benign thecoma. Histology revealed the left ovarian cystic tumor (multilocular, 6.4 x 4.8 x 2.8 cm) was a mature cystic teratoma containing skin, fatty tissue and respiratory epithelial tissue. In addition, there was a small focal adenocarcinomatous lesion contiguous to the teratomatous ciliated columnar epithelium without stromal invasion (so-called adenocarcinoma in situ) that was suggestive of respiratory epithelium origin. However, goblet cells were present in the glandular structures of the lesion and immunohistochemical staining was segmentally strongly positive for CK20 and uniformly negative for CK7. These results suggested that the adenocarcinomatous lesion had a mucin secretory gastrointestinal phenotype. Further investigation and the collection of more cases is necessary to determine the origin and growth mechanism of adenocarcinoma arising from mature cystic teratoma of the ovary.

Adenocarcinoma↗

Synchronous anal and penile cancers.

Malignancies of the anogenital region have similar etiology, including viral infections, sexual habits, social and educational factors. Condylomata acuminata represent precancerous lesions. In the available literature, we found no cases of synchronous cancers of anus and penis reported. We report a case of synchronous cancer of the penile foreskin and cancer of the anus in a 36 year-old man. The microscopic diagnosis of the anal lesion was squamous cell cancer, basaloid type. The penile lesion was squamous cell cancer, keratinizing type. Both cancers presented with the in situ component. Immunohistochemical staining (MIB-1) and histological features (koilocytosis, acanthosis and dyskeratosis) indirectly confirmed the past viral infection. Numerous etiological similarities in anogenital cancers entail careful clinical inspection in patients with a malignant lesion in this region and suggest searching for possible other concomitant cancers or precancerous lesions.

Adult↗

Radiation-induced carcinoma of the penis.

Two patients with carcinoma of the penis were treated with interstitial radiation. They were cured of their disease for 17 and 21 years respectively and then developed radiation-induced tumours.

Carcinoma, Squamous Cell↗