Yoshiaki Tsukada

Central nervous system metastasis from breast carcinoma autopsy study

Central nervous system (CNS) metastasis was noted in 309 patients of 1044 autopsy cases of breast carcinoma. The brain was involved in 193 cases, and cranial dura in 167 cases. In 82 cases, the cranial dura was the sole site of CNS involvement. Metastasis to the leptomeninges was found in 59 cases, and to the spinal cord and dura in 32 cases. Metastases to the infratentorial portion of the brain was almost as frequent as to the cerebrum. Forty‐two percent of the brain metastasis were single lesions, which is similar to the frequency of solitary metastasis to the brain from malignant tumors as a whole. CNS metastasis occurred more frequently in younger patients than older patients, and the clinical course of these patients was shorter than for those patients without CNS metastasis. CNS metastasis developed in the late stage of the disease, and often was not recognized clinically. Only 31% of the cases were clinically diagnosed or suspected before death. A median survival of these patients after clinical diagnosis of CNS metastasis was 33 days. However, a significant improvement was noted in the clinical diagnosis and median survival in the latter half of the study period. Eleven patients lived for more than 1 year after diagnosis of CNS metastasis. Only 14% of the 309 patients died from CNS failure. Cancer 52:2349‐2354, 1983.

Patterns of metastasis in uterine sarcoma. An autopsy study

The autopsy findings of 73 patients with uterine sarcoma were studied to determine the sites and possible modes of metastasis. Homologous mixed mesodermal tumors were the most frequent (41%) followed by leiomyosarcoma (26%), heterologous mixed mesodermal tumor (18.3%), stromal sarcoma (12%), and endolymphatic stromal myosis (3%). The peritoneal cavity and omentum were the most frequently involved sites (59%), followed by the lung (52%), pelvic lymph nodes (41%), paraaortic lymph nodes (38%), and liver parenchyma (34%). The presence of lung metastasis was not associated with pelvic or paraaortic node metastasis or intraperitoneal disease. Metastasis to other distant sites including the brain, heart, kidney, and bone were independent of pelvic and paraaortic nodal metastasis or intraperitoneal disease. Metastatic sites were not different among various histologic types. Distant metastatic sites were statistically associated with lung metastasis. Hematogenous metastasis best explains this metastatic pattern and adjuvant systemic therapy seems indicated.

Intraoperative frozen section diagnosis of depth of myometrial invasion in endometrial adenocarcinoma

Abstract From January 1981 to December 1988, a prospective trial was conducted on 216 consecutive patients undergoing hysterectomy for FIGO stage I endometrial adenocarcinoma to determine the accuracy of intraoperative frozen section (IFS) diagnosis of depth of myometrial invasion. IFS and D&C diagnoses were compared to the permanent section diagnosis to determine their accuracy. Patients with an IFS or D&C diagnosis of grade 3 carcinoma, deep myometrial invasion, cervical invasion, or adnexal involvement were considered high risk for paraaortic nodal metastasis, and paraaortic lymphadenectomy was performed. IFS correctly diagnosed the depth of myometrial invasion in 194 of 204 cases (95%). The sensitivity of IFS diagnosis of deep invasion was 87%, the specificity was 99%, the positive predictive value was 98%, and the negative predictive value was 94%. Grade, subtype, cervical invasion, and adnexal involvement were also accurately diagnosed. Based on IFS and D&C diagnosis, paraaortic lymphadenectomy was performed in 32% of patients, while 68% were considered low risk and were spared paraaortic lymphadenectomy. Eight patients (5%) were incorrectly diagnosed as low risk and did not have paraaortic lymphadenectomy performed. Sixty-five of seventy-three (90%) patients considered high risk on permanent section had paraaortic lymphadenectomies performed on the basis of IFS and D&C diagnosis. Inaccurate IFS diagnosis of depth of myometrial invasion can occur when tumor involves the uterine isthmus or cornua and when tumor invades areas of adenomyosis.

Metastatic tumor to the tongue. Report of twelve cases.

Abstract The authors have reviewed twelve autopsies of metastatic tumors to the tongue. All twelve cases had documented primary tumors in extraoral sites. This rare phenomenon occurred mostly in patients with generalized dissemination of tumor. Four of the twelve patients had clinical manifestations of lingual metastases before death. In this reported series, most metastases were discovered in the basal region of the tongue.

Histopathology, FIGO stage, and BRCA mutation status of ovarian cancers from the Gilda Radner Familial Ovarian Cancer Registry.

Studies of the histopathology of ovarian cancer arising in patients with germline mutations in BRCA1 or BRCA2 have shown inconsistent findings. We analyzed the large number of tumors from women enrolled in the Gilda Radner Familial Ovarian Cancer Registry for correlations between histopathology and BRCA mutation status. Histopathology slides and reports were reviewed for histology, grade, and stage for cancers of the ovary or peritoneum in 220 women from 126 Gilda Radner Familial Ovarian Cancer Registry families. At least one affected member of each family was analyzed for mutations in the BRCA1 and BRCA2 genes, and tumors from mutation-positive families were compared with those from mutation-negative families. Of 70 patients from 38 BRCA1-positive families, 69 had epithelial ovarian carcinoma and one had a dysgerminoma. Fifteen of 16 patients from nine BRCA2-positive families had epithelial ovarian cancer, and one had a primary peritoneal cancer. Of 134 patients from 79 BRCA-negative families, 118 had epithelial ovarian carcinoma, 11 had ovarian borderline tumors, three had nonepithelial tumors, and two had primary peritoneal carcinoma. There were fewer grade 1 (p < 0.001) and stage I (p = 0.005) cancers in patients from BRCA-positive families than in patients from BRCA-negative families. Neither mucinous nor borderline tumors were found in the BRCA-positive families. In conclusion, ovarian cancers arising in women from BRCA-positive families are more likely to be high-grade and have extraovarian spread than tumors arising in women from BRCA-negative families. Borderline and mucinous tumors do not appear to be part of the phenotype of families with germline mutations in the BRCA genes.

Histopathology of familial ovarian tumors in women from families with and without germline BRCA1 mutations

Breast cancers from patients with germline BRCA1 mutations show characteristic histopathologic features. However, similar studies of BRCA1-associated ovarian cancers have reported inconsistent findings. Interobserver differences in histopathologic classification are a significant source of variation, and most studies have obtained histopathologic information from pathology reports rather than from review of histopathology slides. We therefore reviewed the histopathology slides and pathology reports to determine histologic type, grade, and stage for cancers of the ovary or peritoneum in 217 women from 126 families enrolled in the Gilda Radner Familial Ovarian Cancer Registry. Peripheral blood DNA from at least 1 affected member of each family was analyzed for BRCA1 mutations, and tumors from BRCA1 mutation-positive families were compared with those from BRCA1-negative families. Of 66 patients from 36 BRCA1-positive families, 64 had ovarian carcinoma, 1 had an ovarian carcinoma in situ, and 1 had a dysgerminoma. Of 151 patients from 90 BRCA1-negative families, 135 had ovarian carcinoma, 10 had ovarian borderline tumors, 3 had ovarian sex cord/stromal tumors, and 3 had primary peritoneal carcinoma. There were fewer grade 1 (P <.001) and stage I (P =.10) cancers in patients from BRCA1-positive families than in patients from BRCA1-negative families. Neither mucinous nor borderline tumors were found in the BRCA1-positive families. Ovarian cancers arising in women from BRCA1-positive families are more likely to be high grade and nonmucinous than cancers arising in women from BRCA1-negative families. The absence of borderline tumors in patients from BRCA1-positive families adds to accumulating evidence that BRCA1 mutations do not play a role in the development of these tumors. HUM PATHOL 31:1420-1424.

Brain metastasis from prostatic carcinoma

Between 1959 and 1971 there were 91 patients with clinically diagnosed prostatic carcinoma who were autopsied at Roswell Park Memorial Institute. In four of these 91 (4.4%) intracerebral metastasis were found at autopsy, but only in one of these four was the diagnosis arrived at pre‐mortem. This report describes the diagnosis and management of intracerebral metastasis from prostate carcinoma. It appears, on the basis of our initial experience, that the clinical diagnosis of this entity deserves more frequent consideration.

Peritoneal papillary carcinoma

Between 1977 and 1986, 325 patients with a diagnosis of ovarian carcinoma, peritoneal cancer, or malignant mesothelioma were reviewed with identification of 23 patients (7%) having peritoneal papillary cancer. Only 2 patients had disease confined to the pelvis and the rest had widespread abdominal disease. Various combination chemotherapeutic agents were used with over a 65% response rate to first-line chemotherapy. Twenty of the 23 patients received cisplatin combination chemotherapy with an overall response rate of 65%.

Conservative therapy for melanoma of the vulva

Recent cooperative studies have demonstrated that less radical local resection of cutaneous melanomas is equally effective as a traditional radical approach. A retrospective review of vulvar melanoma was undertaken to determine if mode of therapy affected recurrence. Survival correlated independently with depth of invasion and age (p = 0.05 and p less than 0.02, respectively). In the comparison of radical vulvectomy with local excision, no patient differences in age or histopathologic variables were determined (nodal disease status, histology, mitotic count, lymphocytic infiltration, or ulceration). Radical vulvectomy did not improve survival over local therapy (p greater than 0.2). Six of eight patients whose melanoma had less than 2 mm of invasion treated with local therapy are disease free after a median of 127 months (range 6 to 300 months). For local excision, recurrences were more frequent when margins were less than 2 cm, but this was not statistically significant in this small sample. Although the current series is small and retrospective, its findings suggest that treatment recommendations of large cutaneous nonvulvar melanoma studies are applicable to vulvar melanoma. A prospective randomized study of radical versus conservative surgery for vulvar melanoma will be necessary to confirm these treatment recommendations.

Clear-cell adenocarcinoma (“mesonephroma”) of the vagina. Three cases associated with maternal synthetic nonsteroid estrogen therapy

Three cases of clear‐cell adenocarcinom of the vagina occurring in adolescence are reported. During embryonic development of all these patients, their mothers were treated with synthetic nonsteroid estrogen. This hormonal therapy during pregnancy should be considered potentially carcinogenic to the embryo and avoided whenever possible. Two of our 3 patients died 28 months and 13 months after primary surgical treatment and combined ionizing radiation therapy and chemotherapy, respectively. It is important to include malignancy in the differential diagnosis of vaginal bleeding in teenagers.