Krukenberg tumors of the ovary: a clinicopathologic analysis of 120 cases with emphasis on their variable pathologic manifestations.

120 Krukenberg tumors were analyzed with emphasis on their wide microscopic spectrum and resultant problems in differential diagnosis. The patients ranged from 13 to 84 years (average, 45 years) with 43% of them under 40 years. Abdominal swelling or pain usually accounted for the clinical presentation, but 17 had abnormal vaginal bleeding, 4 had virilization, and 4 had hirsutism without virilization. Ascites was present in 43% of the cases. Sixty-three percent of the tumors were documented to be bilateral, but both ovaries were not always removed or rigorously examined microscopically. The mean diameter of the tumors was 10.4 cm, and they typically had intact, bosselated external surfaces without adhesions. The sectioned surfaces were typically solid and firm to edematous to gelatinous; one third of the tumors also had cysts. Microscopic examination showed great variation from case to case and within individual neoplasms. Multiple nodules separated by normal stroma were seen in small neoplasms and focally in many larger ones. The tumors were often more cellular at their periphery and edematous to gelatinous centrally. An irregular distribution of cellular and less cellular areas often imparted a pseudolobular pattern. The cellularity of the stroma ranged from densely cellular to paucicellular; the latter regions ranged from edematous to mucoid. The overall morphology varied according to the prominence of signet-ring cells, extracellular mucin, edema, and various epithelial patterns. Signet-ring cells were numerous in most neoplasms (and by definition occupied at least 10% of the neoplasm) but were often absent or inconspicuous in significant areas of them. The signet-ring cells typically had modest but sometimes copious amounts of pale to basophilic cytoplasm; occasionally, it was eosinophilic. The signet-ring cells varied widely in their arrangement, growing singly, in clusters, forming confluent masses or pseudo-tubular arrays or lining part of all of a true tubule. Small glands and tubules were common, often resembling microcysts (when the lining cells were flattened) or Sertoli tubules; mucinous glands and cysts and medium-sized to large intestinal-type glands were also relatively common, particularly the latter. Extracellular mucin was often conspicuous and, when associated with scant acellular collagenous stroma, gave a distinctive appearance referred to by us as "feathery degeneration." Stromal luteinization was present in the tumors of the 8 pregnant patients and was seen in 14% of the nonpregnant patients. Unusual features that complicated the microscopic picture included diffuse sheets or other arrangements of mucin-free indifferent cells, squamous cells, clear cells, transitional cells, and corded, trabecular, and insular patterns. Vascular space invasion was common. Two thirds of the primary carcinomas were detected synchronously with, or subsequent to, detection of the Krukenberg tumor compounding the diagnostic difficulty posed by the cases. Two thirds of the primary tumors were in the stomach; other primary sites in order of frequency were appendix, colon, breast, small intestine, rectum, gallbladder, and urinary bladder. Our observations emphasize that the microscopic spectrum of the Krukenberg tumor is broader that often presented in the literature, in particular tubules, glands, and cysts often being present, and the wide pathologic differential diagnosis is discussed.

Placental site trophoblastic tumor: A study of 55 cases and review of the literature emphasizing factors of prognostic significance.

OBJECTIVE: The placental site trophoblastic tumor is a rare form of gestational trophoblastic disease. Fifteen percent of reported cases have been fatal, but predicting behavior in individual patients has been challenging. METHODS: The clinical, gross and histopathological features of 55 cases and 180 cases in the literature were analyzed for their effect on survival and in relation to tumor stage. RESULTS: The 55 patients in our series were 20 to 62 (average 32) years of age. The tumors occurred on an average of 34 months after the last known gestation. 84% were stage I, 2% stage II, 5% stage III, and 9% stage IV. Serum levels of human chorionic gonadotropin (hCG) were elevated (average 691 mIU/ml) in 77% of the cases. The tumors were on average 5 cm in greatest dimension and were composed microscopically of infiltrative sheets of intermediate (extravillous) trophoblastic cells. The mitotic rate ranged from 0 to 20 (average 5.0) per 10 high power fields. The follow-up interval averaged 4.6 years. Eight patients (15%) died from metastatic tumor, and nine additional patients had metastases or a recurrence but were alive at last contact. The most common metastatic sites were the lungs, liver, and vagina. CONCLUSIONS: Significant factors associated with adverse survival in the present series were age over 35 years (P = 0.025), interval since the last pregnancy of over 2 years (P = 0.014), deep myometrial invasion (P = 0.006), stage III or IV (P < 0.0005), maximum hCG level > 1000 mIU/ml (P = 0.034), extensive coagulative necrosis (P = 0.024), high mitotic rate (P = 0.005), and the presence of cells with clear cytoplasm (P < 0.0005). Only stage and clear cytoplasm were independent predictors of overall survival, while stage and age were the only independent predictors of time to recurrence or disease-free survival. In the literature, factors associated with survival were stage (P < 0.005), interval from preceding pregnancy of over 2 years (P = 0.029), previous term pregnancy (P = 0.046), high mitotic rate (P < 0.0005), and high hCG level (P = 0.037).

Unusual epithelial and stromal changes in myoinvasive endometrioid adenocarcinoma: a study of their frequency, associated diagnostic problems, and prognostic significance.

The authors have noted that when the myoinvasive glands of endometrioid carcinomas evoke a prominent fibromyxoid stromal reaction, they sometimes undergo distinctive changes. These are characterized by outpouchings from typical neoplastic glands that become detached and often lined by flattened epithelium, sometimes appearing as microcysts. The glands may less often become elongated or undergo fragmentation into small solid clusters or single cells. For this constellation of changes, which in aggregate are distinctive, the authors have coined the acronym MELF (microcystic, elongated, fragmented). The authors evaluated the prognostic significance of these stromal and glandular features and their association with each other and with other histopathologic and clinical prognostic factors by studying 115 unselected myoinvasive endometrial endometrioid carcinomas. The histologic slides and clinical records were reviewed to collect data on age, recurrences or metastases, survival, stromal reaction pattern (fibromyxoid, lymphocytic, or absent), presence of MELF, FIGO grade, depth of myometrial invasion, vascular invasion, squamous differentiation, and presence or absence of necrosis. Factors associated with an unfavorable outcome (recurrence or death) included a fibromyxoid stromal reaction, age older than 70 years, advanced stage, vascular invasion, FIGO grade, depth of myoinvasion, and the presence of tumor necrosis. The presence of a host lymphocytic reaction was associated with a favorable outcome. A multivariate logistic regression model identified stage and age older than 70 years as independent prognostic factors. The MELF changes were associated with the presence of a host stromal reaction (most strongly with a fibromyxoid reaction) and vascular invasion. Within the group associated with a fibromyxoid reaction, patients exhibiting MELF had a better survival. In conclusion, a fibromyxoid reaction in cases of endometrioid carcinoma is associated with a higher frequency of death or recurrence and it is frequently accompanied by distinctive morphologic changes (MELF) in myoinvasive glands as well as lymphatic or blood vessel invasion. MELF is associated with a fibromyxoid reaction but is not independently associated with an adverse effect on prognosis. A lymphocytic stromal reaction is associated with a favorable effect on prognosis and is less often accompanied by the distinctive morphologic changes (MELF) highlighted herein.

Mesodermal (müllerian) adenosarcoma of the ovary: a clinicopathologic analysis of 40 cases and a review of the literature.

Forty cases of mesodermal adenosarcoma of the ovary occurred in women 30-84 years of age (mean 54 years). Abdominal discomfort and distension were the usual complaints. All the patients were treated with an oophorectomy, which was accompanied by a hysterectomy in 85%, a contralateral oophorectomy in 65%, and nonsurgical therapy in 28%. Tumor rupture occurred at or before the operation in 67% of the cases. Twenty-six tumors were stage I, 11 stage II, and 3 stage III. The tumors were unilateral in 97.5% of the cases and 5.5-50 cm (mean 14 cm) in greatest dimension; most of the tumors were predominantly solid but contained numerous small cysts. Microscopic examination revealed sarcomatous overgrowth in 12 tumors. Sex cord-like elements were present in six tumors (including four with sarcomatous overgrowth) and heterologous elements in five (including two with sarcomatous overgrowth). The highest mitotic index of the sarcomatous component was 1-25 (mean 6) mitotic figures per 10 high power fields. Only 6 of 26 women (23%) who were followed postoperatively for > or=5 years were free of tumor. In the other 20 patients recurrent tumor appeared at 0.4-6.6 years (mean 2.6 years) after operation as pure sarcoma (low grade or high grade) or adenosarcoma (with or without sarcomatous overgrowth). Eight women had additional recurrences, and four women had blood-borne metastases. One patient was alive at 15.7 years after the excision of pulmonary metastases. The 5-, 10-, and 15-year survival rates were 64%, 46%, and 30%, respectively. Age <53 years, tumor rupture, a high grade, and the presence of high-grade sarcomatous overgrowth appeared to be associated with recurrence or extraovarian spread. Ovarian adenosarcomas have a worse prognosis than uterine adenosarcomas, presumably because of the greater ease of peritoneal spread. Many of the tumors caused problems in differential diagnosis.

The Prolonged Gestation, Birth, and Early Life of the Sex Cord Tumor with Annular Tubules and How it Joined a Syndrome.

The sex cord tumor with annular tubules was discovered as a distinctive entity when its unusual-appearing microscopic pattern was encountered repetitively in a pathology consultation practice. The author was stimulated to describe the clinicopathological features of the tumor and assign it a specific name when a minority of the cases in his series were found to be associated with the rare Peutz-Jeghers syndrome. Both these tumors and those occurring in the absence of the syndrome have been shown to have distinctive clinicopathological features that differ from those of other tumors in the sex cord-stromal category. Int J Surg Pathol 8(3):233-238, 2000

Uterine Endometrioid Carcinoma with Small Nonvillous Papillae: An Analysis of 26 Cases of a Favorable-Prognosis Tumor To Be Distinguished from Serous Carcinoma.

We have encountered a number of endometrioid carcinomas with small papillary buds lacking fibrovascular cores that could be confused with the small cellular papillae of serous papillary carcinoma (SPC). We have designated these tumors "endometrioid carcinoma with small nonvillous papillae" (ECSP). Because they have not been investigated previously we analyzed 26 examples and compared their features with those of 21 SPCs of the uterus. Three hundred and ninety consecutive cases of endometrial carcinoma diagnosed between January, 1989, and January, 1994, were retrieved from our hospital files; 26 (6.7%) of them, (8% of the endometrioid carcinomas) were identified as ECSP, and 21 (5.4%) as SPC. Tumors were classified as ECSP when the small papillae were present within the glands of otherwise typical endometrioid carcinoma or on the villous projections of villoglandular endometrioid carcinoma. Most of the papillae were in the form of buds of cells with ample eosinophilic cytoplasm and a low nuclear-to-cytoplasmic ratio, but some papillae had a more complex pattern. The papillae arose on a background of International Federation of Gynecology and Obstetrics (FIGO) grade 1 or 2 endometrioid carcinomas, which showed squamous differentiation in half the cases. SPCs were identified according to generally accepted criteria. The mean age of the patients with ECSP was 67 years, intermediate between that of the patients with endometrioid carcinoma lacking small nonvillous papillae (62 years) and that of the patients with SPC (71 years). Patients with ECSP more frequently presented at an earlier stage (73% stage I/II) than those with SPC (29% stage I/II). The overall 5-year survival of patients with ECSP was 84% (95%CI: 0.68-1), more than double that of patients with SPC, 33% (95%CI: 0.10-0.56). ECSP may be confused with SPC on microscopic examination but has clinical and pathological features similar to those of endometrioid carcinoma lacking small nonvillous papillae, and unlike SPC, should be treated in the same manner as the former. Int J Surg Pathol 8(4):279-289, 2000