Intraluminal Calcium Hydroxyapatite Crystals in Breast Carcinoma: An Ultrastructural Study

Sixty-three breast carcinomas were examined by electron microscopy to determine the frequency of calcium hydroxyapatite (apatite) within tumor lumina. Twenty-one adenocarcinomas contained apatite in intracytoplasmic and/or intercellular lumina. Well-differentiated tumors exhibited a higher incidence of apatite (44%), while only 20% of the poorly differentiated tumors contained apatite (7 = +.22). There was no apparent correlation between the presence of apatite and a positive estrogen receptor assay. Ninety-eight adenocarcinomas of other than breast origin (previously processed for electron microscopy) were examined, revealing 2 cases containing apatite in the appropriate locations. The tissue of origin in one case was determined to be ovarian, while the origin of the second case remains undetermined. The ultrastructural finding of apatite in lumina of adenocarcinoma appears to be unusual in that it has only been observed in breast carcinomas and certain ovarian tumors. The presence of apatite within the lumen in addition to other characteristics of an adenocarcinoma may suggest the breast as the primary site.     

Ultrastructural features of solid/trabecular areas in differentiated thyroid carcinoma

The presence of areas exhibiting a solid/trabecular pattern of growth within an otherwise differentiated thyroid carcinoma represents a source of controversy as regards its proper classification and biologic and prognostic significance. The aim of the current study was to investigate the ultrastructural features of solid/trabecular areas in differentiated thyroid carcinoma and to compare those features with the submicroscopic profile of differentiated, poorly differentiated (insular), and undifferentiated (anaplastic) variants of thyroid cancer. The study series included differentiated carcinoma with solid/trabecular areas (3 cases), conventional papillary carcinoma (4 cases), follicular variant of papillary carcinoma (4 cases), poorly differentiated (insular) carcinoma (3 cases), and undifferentiated (anaplastic) carcinoma (3 cases). It was found that the solid/trabecular areas in differentiated carcinoma and poorly differentiated (insular) carcinoma share similar ultrastructural features and overall retain, even if attenuated, many of the submicroscopic attributes of differentiated carcinomas. In particular, nests of neoplastic cells were observed showing a highly developed cytosecretory apparatus and the presence of numerous abortive/rudimentary follicles, and intercellular and intracellular (intracytoplasmic) lumina/canaliculi of variable morphology. The study supports the hypothesis that the solid/trabecular areas do not merely represent an architectural pattern but rather should be regarded as the expression of a process of reduced differentiation similar to that of poorly differentiated (insular) carcinoma.     

Ultrastructural Features of Solid/Trabecular Areas in Differentiated Thyroid Carcinoma

The presence of areas exhibiting a solid/trabecular pattern of growth within an otherwise differentiated thyroid carcinoma represents a source of controversy as regards its proper classification and biologic and prognostic significance. The aim of the current study was to investigate the ultrastructural features of solid/trabecular areas in differentiated thyroid carcinoma and to compare those features with the submicroscopic profile of differentiated, poorly differentiated (insular), and undifferentiated (anaplastic) variants of thyroid cancer. The study series included differentiated carcinoma with solid/trabecular areas (3 cases), conventional papillary carcinoma (4 cases), follicular variant of papillary carcinoma (4 cases), poorly differentiated (insular) carcinoma (3 cases), and undifferentiated (anaplastic) carcinoma (3 cases). It was found that the solid/trabecular areas in differentiated carcinoma and poorly differentiated (insular) carcinoma share similar ultrastructural features and overall retain, even if attenuated, many of the submicroscopic attributes of differentiated carcinomas. In particular, nests of neoplastic cells were observed showing a highly developed cytosecretory apparatus and the presence of numerous abortive/rudimentary follicles, and intercellular and intracellular (intracytoplasmic) lumina/canaliculi of variable morphology. The study supports the hypothesis that the solid/trabecular areas do not merely represent an architectural pattern but rather should be regarded as the expression of a process of reduced differentiation similar to that of poorly differentiated (insular) carcinoma.     

WT-1 assists in distinguishing ovarian from uterine serous carcinoma and in distinguishing between serous and endometrioid ovarian carcinoma

AIMS: It has been suggested that WT-1 is helpful in distinguishing a primary ovarian serous carcinoma (OSC) from a primary uterine serous carcinoma (USC). Since both neoplasms are often disseminated at diagnosis and since USC often spreads to the ovary and vice versa, it may be difficult to ascertain the primary site. This is important, since adjuvant therapies for OSC and USC may differ. WT-1 staining patterns also differ between OSC and ovarian endometrioid carcinoma and so it is possible that WT-1 may assist in the distinction of these two neoplasms, which is sometimes problematic, especially with poorly differentiated tumours. This study aims to document the value of WT-1 in these settings. Cases of ovarian borderline serous tumour, primary peritoneal serous carcinoma (PPSC) and uterine endometrioid carcinoma were also studied. METHODS AND RESULTS: Cases of OSC (n = 38), USC (n = 25) (in five of these cases there was also a component of endometrioid adenocarcinoma), ovarian endometrioid carcinoma (n = 13), uterine endometrioid carcinoma (n = 7), ovarian borderline serous tumour (n = 16) and PPSC (n = 6) were stained with WT-1. Cases were scored on a scale of 0-3, depending on the percentage of positive cells. The intensity of staining was scored as weak, moderate or strong. There was positive nuclear staining of 36 of 38 (94.7%) OSC with WT-1. In most OSC (68.4%), >50% of cells stained positively and staining was usually strong. Five of 25 (20%) USC were positive with only two cases exhibiting staining of >50% of cells. All primary ovarian and uterine endometrioid carcinomas were negative. All PPSC were positive, usually with diffuse strong immunoreactivity. Fourteen of 16 borderline serous tumours exhibited positivity with WT-1. CONCLUSIONS: WT-1 is useful in distinguishing OSC (characteristically diffuse strong nuclear positivity) from USC (characteristically negative). However, rarely OSC is negative and occasional cases of USC are positive. WT-1 may also be helpful in differentiating poorly differentiated OSC from poorly differentiated ovarian endometrioid carcinoma.     

The histogenesis of mucinous adenocarcinoma of the stomach from observations in early gastric cancer.

Eighteen cases of primary mucinous early gastric cancer (EGC) were studied with regard to histogenetic implications. This type of carcinoma was found in 10.7% of 168 cases of EGC and was removed surgically. In 11 patients, mucinous tumor was mainly found in the submucosal layer of the stomach. These findings are in keeping with the hypothesis that mucinous adenocarcinoma develops during progression of an ordinary adenocarcinoma. In two cases of well-differentiated mucinous intramucosal EGC, mucinous tumor was associated with a villous adenoma, as is the case in intestinal-type adenocarcinoma. In five cases of poorly differentiated mucinous carcinoma, tumor was seen at the middle level of the mucosa, with normal foveolae in the upper mucosa and normal specialized antral and body type glands in the lower part. There were no associated areas of dysplasia or intestinal metaplasia. These histologic findings suggest that a subset of mucinous EGC develops from the proliferative zone (the neck region) of nonmetaplastic glands, as reported in diffuse carcinoma of the stomach. These results suggest a histogenetic heterogeneity in the entity of the mucinous carcinoma. Well- and poorly differentiated mucinous intramucosal EGCs show a histogenesis similar to that of gastric carcinoma of the intestinal and diffuse types, respectively.     

Urachal adenocarcinoma metastatic to the ovary simulating primary mucinous cystadenocarcinoma of the ovary: report of a case

A 56-year-old woman had a large multicystic ovarian tumour 4 years after undergoing partial cystectomy for a deeply invasive urachal adenocarcinoma. On microscopic examination the ovarian tumour was a moderately differentiated mucinous cystadenocarcinoma similar to the urachal tumour. Several peritoneal biopsies and the omentum were positive for metastatic adenocarcinoma. Although initially interpreted as representing primary mucinous adenocarcinoma of the ovary with peritoneal spread, subsequent comparison with the previous urachal adenocarcinoma led to re-interpretation of the ovarian tumour as metastatic urachal carcinoma. Metastatic mucinous adenocarcinomas involving the ovary may be misinterpreted as primary ovarian carcinomas and the urinary bladder is a potential source of these neoplasms.     

Papillary serous carcinoma of the ovary: an ultrastructural and immunohistochemical study

Twenty-four patients with ovarian serous papillary carcinoma were enrolled in the present ultrastructural and immunohistochemical study. Immunohistochemistry was used to examine the status of proliferation activity with antibodies against Ki67 and BM28, and the status of EGFR family members with antibodies against EGFR, c-erbB-2, and c-erbB-4. Ultrastructurally, poorly differentiated tumors often revealed solid sheets of tumor cells with variable desmosomes, cell connection complexies, and microvilli. No mature cilia, which are often present in benign and borderline ovarian epithelial tumors, were seen in these 24 carcinomas. However, two poorly differentiated tumors demonstrated oligocilia. In addition, numerous secondary lysosomes and bizzare intracytoplasmic pseudocavities were more often present in the poorly differentiated tumors. Immunohistochemically, strong expressions of BM28 and Ki67 in more than 50% of the tumor cells were found in 12/15 (80%) and 11/15 (73%) of the poorly differentiated tumors, respectively, compared with 3/9 (33%) and 1/9 (11%) of the moderately differentiated tumors, respectively. Higher levels of EGFR and c-erbB-2 expressions were more often observed in the poorly differentiated tumors, compared with that in the moderately differentiated tumors. In conclusion, oligocilium, numerous secondary lysosomes, and bizarre intracytoplasmic inclusions are more often seen in poorly differentiated ovarian serous carcinomas. Poorly differentiated ovarian serous carcinomas express higher levels of Ki67, BM28, EGFR, and c-erbB-2 proteins.     

Microsatellite-unstable mucinous colorectal carcinoma occurring in the elderly: comparison with medullary type poorly differentiated adenocarcinoma

Mucinous carcinoma and poorly differentiated adenocarcinoma of the large intestine have a high frequency of microsatellite instability, and their occurrence increases gradually with age. To elucidate the clinicopathological and immunohistochemical features of microsatellite-unstable mucinous carcinoma and compare the tumor with medullary type poorly differentiated adenocarcinoma, the clinicopathological status and expression of mucin core and hMLH1 proteins were studied in 15 microsatellite-unstable and 20 microsatellite-stable mucinous colorectal carcinomas occurring in elderly patients, and compared with 23 cases of medullary type poorly differentiated adenocarcinoma in which 21 cases were microsatellite-unstable. Thirteen (87%) of 15 microsatellite-unstable carcinomas exhibited absent hMLH1 expression compared with three (15%) of 20 microsatellite-stable carcinomas (P < 0.01). The proportion (87%) of positive MUC5AC expression in microsatellite-unstable mucinous carcinoma was significantly higher than that (45%) in microsatellite-stable mucinous carcinoma (P = 0.01). Compared with microsatellite-stable mucinous carcinoma, microsatellite-unstable mucinous carcinomas were significantly associated with a proximal location, intra- and peritumoral inflammatory cell infiltration, frequent MUC5AC expression, a low incidence of lymph node metastasis and absent hMLH1 protein expression, which is not different to medullary type poorly differentiated adenocarcinoma except for MUC2 expression and age-related occurrence. These results suggest that microsatellite-unstable mucinous carcinoma occurring in the elderly shares clinicopathological and molecular features with medullary type poorly differentiated adenocarcinoma and that microsatellite instability with absent hMLH1 expression plays an important role in the development of these two carcinomas.     

Metastatic ovarian carcinoma of large intestinal origin simulating primary ovarian carcinoma. A clinicopathologic study of 25 cases.

The distinction of metastatic ovarian carcinoma from a primary malignant ovarian neoplasm is crucial to its subsequent management. The most common metastatic carcinoma that mimics primary ovarian carcinoma is that of large bowel origin. The clinical and pathologic features of 25 cases of intestinal adenocarcinoma metastatic to the ovaries were analyzed. The patients ranged in age from 47 to 80 years (average age, 60 years). Most patients had abdominal pain and a pelvic mass. In 56%, the ovarian tumors and the large bowel carcinomas were discovered synchronously; 44% were metachronous. Seventy-five percent of the tumors were unilateral. Gross examination revealed that all the ovarian tumors were solid and cystic with smooth outer surfaces. Most of the tumors showed hemorrhage and necrosis. Histologic examination showed that 13 cases had a predominantly endometrioid-like pattern, four cases were predominantly mucinous, and the rest demonstrated a mixed pattern. The presence of a garland pattern with cribriform areas and "dirty" necrosis were the most distinctive features that were helpful in correctly differentiating these tumors from primary endometrioid ovarian carcinoma, with which they are often confused. Immunohistochemical stains for carcinoembryonic antigen showed strong intracytoplasmic positive staining in all the cases of intestinal adenocarcinoma metastatic to the ovaries, in contrast to primary ovarian endometrioid carcinoma, which stain negatively for carcinoembryonic antigen or show only intraluminal or apical positivity. As expected, intestinal adenocarcinoma metastatic to the ovaries had a very poor prognosis. Seventy percent of the patients died within a period of 1 to 19 months (average, 8.2 months). Its distinction from primary ovarian carcinoma is crucial because the management and prognosis of metastatic ovarian carcinoma of large intestine origin is different.     

Distribution of alpha glutathione S-transferase in ovarian neoplasms: an immunohistochemical study

AIMS: Alpha glutathione S-transferase (alpha-GST) has been shown to be an immunohistochemical marker for delta(4-5) isomerase, an enzyme active in steroidogenesis. The purpose of this study was to document the distribution of alpha-GST in ovarian neoplasms in order to evaluate its usefulness as a diagnostic tool. METHODS AND RESULTS: A total of 92 tumours (25 sex cord/stromal, 53 epithelial and 14 germ cell) were subjected to immunohistochemistry using a commercially available polyclonal antibody to alpha-GST. The avidin-biotin complex was used as a detection system. Positive staining was found in luteinized stromal cells of all tumour types (58/92). This included the Leydig cells of Sertoli-Leydig cell tumours (7/7) and was particularly prominent in the stromal cells of both benign and malignant mucinous tumours (24/25). Granulosa and Sertoli cells showed weak or no intracytoplasmic staining, which is expected because they do not normally produce androstenedione. They did show some intranuclear staining. Malignant mucinous (12/25) and occasional other epithelial tumours showed focal intracytoplasmic positive staining. Yolk sac tumours showed focal positivity (7/8). CONCLUSIONS: Intracytoplasmic staining of stromal cells is considered to indicate steroidogenesis and intranuclear staining the intracytoplasmic transport function of alpha-GST. The intracytoplasmic staining of mucinous carcinomas might represent an up-regulation of some detoxification function. The findings suggest that antibody to alpha-GST has some value in the investigation of ovarian pathology and could readily be included in any panel of antibodies used to investigate ovarian neoplasms of uncertain histogenesis.     

The Diagnostic Significance of Intracytoplasmic Lumina in Metastatic Neoplasms

The diagnostic significance of intracytoplasmic lumina (ICL) was evaluated in a series of 61 consecutive and unselected metastatic neoplasms in lymph nodes, soft tissues, and bone studied by light and electron microscopy. Their only common denominator was a light microscopic diagnosis of “metastatic tumor of unknown primary site.”

With only rare exceptions, all previous reports of ICL on neoplastic cells deal with glandular organs or organs in which a glandular “metaplasia” may occur. Since primary or metastatic lesions of poorly differentiated squamous carcinomas, melanomas, and lymphomas may often cause problems in the differential diagnosis of poorly differentiated metastases, we also studied a large series of these neoplasms to see if they exhibited ICL.

Our study shows that when ICL are present in a metastatic carcinoma of undetermined primary site, the breast is the most likely site of the primary tumor, but that the clinical context may, and often does, modify the validity of this criterion. Our demonstration of ICL in two adnexal carcinomas of sweat and meibomian glands should discourage pathologists from jumping to a conclusion of a metastatic breast carcinoma whenever ICL are found in a tumor in the skin.

The presence of ICL seems to rule out the possibility of the neoplasm being a squamous carcinoma, a lymphoma, or a malignant melanoma.

Histochemical techniques were useful in diagnosing cases of mesotheliomas and adenomatoid tumors in which ICL are positive with Alcian blue but become negative after hyaluronidase digestion. The notion that mucicarmine positivity might exclude breast carcinoma was not confirmed in our study.     

The Diagnostic Significance of Intracytoplasmic Lumina in Metastatic Neoplasms

The diagnostic significance of intracytoplasmic lumina (ICL) was evaluated in a series of 61 consecutive and unselected metastatic neoplasms in lymph nodes, soft tissues, and bone studied by light and electron microscopy. Their only common denominator was a light microscopic diagnosis of “metastatic tumor of unknown primary site.”

With only rare exceptions, all previous reports of ICL on neoplastic cells deal with glandular organs or organs in which a glandular “metaplasia” may occur. Since primary or metastatic lesions of poorly differentiated squamous carcinomas, melanomas, and lymphomas may often cause problems in the differential diagnosis of poorly differentiated metastases, we also studied a large series of these neoplasms to see if they exhibited ICL.

Our study shows that when ICL are present in a metastatic carcinoma of undetermined primary site, the breast is the most likely site of the primary tumor, but that the clinical context may, and often does, modify the validity of this criterion. Our demonstration of ICL in two adnexal carcinomas of sweat and meibomian glands should discourage pathologists from jumping to a conclusion of a metastatic breast carcinoma whenever ICL are found in a tumor in the skin.

The presence of ICL seems to rule out the possibility of the neoplasm being a squamous carcinoma, a lymphoma, or a malignant melanoma.

Histochemical techniques were useful in diagnosing cases of mesotheliomas and adenomatoid tumors in which ICL are positive with Alcian blue but become negative after hyaluronidase digestion. The notion that mucicarmine positivity might exclude breast carcinoma was not confirmed in our study.     

Morphological subtypes of ovarian carcinoma: a review with emphasis on new developments and pathogenesis

Ovarian carcinomas comprise a heterogeneous group of neoplasms, the four most common subtypes being serous, endometrioid, clear cell and mucinous. In recent years, our understanding of the underlying pathogenesis and initiating molecular events in the different tumour subtypes has greatly increased, and although ovarian carcinoma is often considered clinically as one disease, there is now a much greater realisation that the various subtypes have a different natural behaviour and prognosis. At present, adjuvant therapy is mainly dependent upon tumour stage and grade rather than type; however, this is likely to change in the future with the development of new chemotherapeutic agents and targeted therapies and clinical trials are necessary to evaluate the efficacy of different agents in clear cell, mucinous and low grade serous carcinomas, neoplasms which are considered relatively resistant to traditional chemotherapeutic regimes. In this review, the major subtypes of ovarian carcinoma are discussed. It is now firmly established that there are two distinct types of ovarian serous carcinoma, low grade and high grade, the former being much less common and arising in many cases from a serous borderline tumour. Low grade and high grade serous carcinoma represent two distinct tumour types with a different underlying pathogenesis rather than low grade and high grade variants of the same neoplasm. Both are usually advanced stage (stage III or IV) at diagnosis. B-raf and k-ras mutations are important molecular events in low grade serous carcinomas while high grade serous carcinomas are almost always associated with TP53 mutation. There is now emerging and compelling evidence that many high grade serous carcinomas (by far the most common subtype of ovarian carcinoma) actually arise from the epithelium of the distal fallopian tube. Future studies regarding the initiating molecular events in the development of this aggressive neoplasm should concentrate on this site. Primary ovarian mucinous carcinomas are uncommon, almost always unilateral and stage I, and largely of so-called intestinal or enteric type. Most arise in a stepwise manner from a pre-existing mucinous cystadenoma and mucinous borderline tumour. Endometrioid and clear cell carcinomas typically present as low stage neoplasms and in many, or most, cases arise from endometriosis; the former are usually well differentiated and there is now evidence that the majority of neoplasms reported in the past as high grade endometrioid carcinoma are of serous type. WT1 is useful in this regard since it is a relatively specific marker of a serous phenotype. It is recommended that different subtypes of ovarian carcinoma are graded using different systems rather than employing a universal grading system.     

Glycogen-rich clear cell carcinoma of the breast: a solid variant with mucus. A light microscopic, immunohistochemical and ultrastructural study of a case

The light microscopic, immunohistochemical and ultrastructural features of a clear cell carcinoma of the breast have been studied. Both intraductal and invasive components were found. Histochemistry showed large amounts of intracytoplasmic glycogen and sparse neutral mucin in the tumour. The tumour cells were stained by antisera to carcinoembryonic antigen, keratin and epithelial membrane antigen, but not by antisera to alpha-lactalbumin, desmin or vimentin. Ultrastructurally, the epithelial derivation of the tumour was confirmed. Only a few intracytoplasmic lumina were demonstrated. The tumour was classified as a mucin-containing variant of glycogen-rich, clear cell carcinoma of the breast.     

Uncommon ovarian epithelial tumours

Epithelial ovarian tumours represent the most common type of ovarian tumour. Most of malignant cases represent high-grade serous, clear cell and endometrioid carcinomas; borderline serous and mucinous tumours of intestinal type are less common. This review focuses on the uncommon or rare epithelial tumours of the ovary which include borderline and malignant Brenner tumours, the recently-described mesonephric-like carcinoma of the ovary, and primary ovarian neuroendocrine tumours, with emphasis on helpful and diagnostic features.     

Intracytoplasmic lumina in bladder carcinomas

Intracytoplasmic lumina were identified in neoplastic cells from four human and three canine "spontaneous" bladder carcinomas. They were also found in N-[4-(5-nitro-2-furyl)-2-thiazoly] formamide induced bladder carcinomas in rats as well as in cultured tumor cell lines derived from these experimental tumors. Intracytoplasmic lumina were readily recognized in 5 micrometer. paraffin embedded and 1 micrometer. epoxy embedded sections. Histochemically, intracytoplasmic lumina were strongly positive with PAS and alcian blue-PAS; mucicarmine stain was positive as unevenly distributed droplets. Ultrastructurally lumina were defined by a symmetric unit membrane; they displayed abundant pleomorphic microvilli, which contained prominent cytoskeletal elements. Step section electron microscopic study revealed continuity between intracytoplasmic lumina and the extracellular space in only one case of experimental bladder carcinoma; otherwise they appeared to be entirely encompassed within the cytoplasm. No instance of exocytosis in relation to intracytoplasmic lumina was found. Our observations suggest that intracytoplasmic lumina may be rather frequent in several forms of urothelial carcinoma. They appear to be predominantly but not invariably intracytoplasmic. The mechanism that may determine the development of continuity between intracytoplasmic lumina and the extracellular space and the adduced relationship between intracytoplasmic lumina and the process of secretion remain undetermined.     

Patterns of immunohistochemical staining for proliferating cell nuclear antigen and p53 in benign and neoplastic human endometrium

Signet ring cell differentiation in adenocarcinoma of the prostate is uncommon. In a review of 200 cases of prostatic carcinoma, we identified five cases with this change, all in moderately to poorly differentiated prostatic carcinomas. The signet ring cells in prostatic carcinoma contain an intracytoplasmic lumen, shown on electronmicroscopy to be lined by microvilli. Transition stages were seen from solid to acinar to signet ring cells to mucinous variants. We believe that this change is part of the spectrum of appearances of prostatic carcinoma and should not be regarded as a subtype of specific significance.     

The fine structure of large cell undifferentiated carcinoma of the lung. Evidence for its relation to squamous cell carcinomas and adenocarcinomas

The light microscopic diagnosis of large cell undifferentiated carcinoma of the lung is known to be highly subjective and shows poor interobserver reproducibility; the very existence of this tumor as a separate entity has been challenged. The ultrastructure of seven large cell undifferentiated carcinomas was examined in an attempt to determine whether they were merely poorly differentiated adenocarcinomas and squamous cell carcinomas, or actually represented an entirely separate class of tumors. Four large cell undifferentiated carcinomas demonstrated intra- and intercellular lumina and were designated adenocarcinomas. In three cases there were well formed desmosomes with numerous tonofilaments and intercellular bridges. These tumors were classified as squamous cell carcinomas. An eighth tumor metastatic to the abdominal wall also showed the features of squamous carcinoma. In addition, all tumors contained a variable population of primitive cells without identifying features. The large cell undifferentiated carcinomas were compared ultrastructurally with eight cases of poorly differentiated adenocarcinomas and squamous cell carcinomas classified by light microscopy. These tumors were morphologically similar, but contained fewer primitive cells and greater numbers of differentiated cells. Cells with a clear cytoplasm as seen by light microscopy were present in both the large cell undifferentiated and poorly differentiated groups; these cells contained variable amounts of glycogen but were otherwise similar to the nonclear cells. It is suggested that most of the subcategories of large cell undifferentiated carcinoma represent very poorly differentiated adenocarcinomas and squamous carcinomas.     

Pathology of primary and metastatic mucinous ovarian neoplasms

Recent years have seen a dramatic change in the pathological approach to ovarian mucinous neoplasms. A substantial proportion of tumours previously considered to be ovarian primaries actually represent secondary ovarian involvement by tumours elsewhere in the body. Two major categories of tumour have completely disappeared from the diagnostic spectrum: ovarian 'borderline' mucinous tumour associated with pseudomyxoma peritonei, and widely disseminated mucinous carcinomas. The emergent picture of true ovarian primary carcinoma of pure mucinous morphology is that this is a rare malignancy that is low grade and low stage at presentation in the vast majority of cases, with a very low likelihood of aggressive clinical behaviour. A large volume of literature has appeared concerning the pathological distinction of primary from metastatic ovarian mucinous neoplasms in view of the dramatically different prognosis and treacherously similar morphology. Clinicopathological parameters useful in the distinction of primary from metastatic mucinous ovarian carcinomas are reviewed. Major features favouring metastases are bilaterality, size <10 cm, surface involvement, extensive intra-abdominal spread and an extensive infiltrative pattern with desmoplasia. Two morphological patterns essentially exclude ovarian origin: colloid and signet ring carcinomas. Features favouring primary ovarian origin are unilaterality, large size >12 cm, smooth external surface and association with other ovarian pathology. An admixture of benign, borderline and malignant patterns in the same tumour favour primary origin, but can be misleading as a 'maturation' pattern in metastases can result in the same appearance.