p63 expression in breast cancer: a highly sensitive and specific marker of metaplastic carcinoma

p63, a member of the p53 gene family, is involved in cellular differentiation and is expressed in the nuclei of myoepithelial cells of normal breast ducts and lobules. Although p63 has been reported in metaplastic carcinomas of the breast, its expression pattern in breast carcinomas and sarcomas has not been fully characterized, and its potential diagnostic utility has not been defined. In this study, we determined p63 expression in a large number of breast carcinomas, including metaplastic carcinomas, and in Phyllodes tumors and sarcomas. We examined 189 invasive breast carcinomas, including 15 metaplastic carcinomas, as well as 10 Phyllodes tumors, and 5 pure sarcomas of the breast for pattern and intensity of p63 staining using an anti-p63 antibody (clone 4A4, Neomarkers). p63 was strongly expressed in 13 of 15 metaplastic carcinomas (86.7%). p63 was positive in all the metaplastic carcinomas with spindle cell and/or squamous differentiation (12 of 12), and in 1 of 3 metaplastic carcinomas with cartilage foci. In stark contrast, only 1 of 174 (0.6%) nonmetaplastic invasive carcinomas was positive for p63. All Phyllodes tumors and sarcomas were consistently negative for p63 expression. The sensitivity and specificity of p63 as a diagnostic marker for metaplastic carcinoma was 86.7% and 99.4%, respectively. We propose the inclusion of p63 as part of the diagnostic workup of challenging spindle cell tumors of the breast as a highly specific marker for metaplastic carcinomas.     

Immunohistochemical staining with monoclonal Ab B72.3 in benign and malignant breast disease

A variety of benign and malignant breast lesions were evaluated for their reactivity with the monoclonal antibody B72.3. The lesions included invasive duct carcinoma (15 cases), apocrine carcinoma (18 cases, nine invasive and nine in situ lesions), well-differentiated (tubular) carcinoma (15 cases), invasive lobular carcinoma (10 cases) and lobular neoplasia (10 cases), intraductal hyperplasia (nine cases), atypical intraductal hyperplasia (eight cases), intraductal carcinoma (15 cases), sclerosing adenosis (15 cases), and apocrine metaplasia (24 cases). Only 20% of the invasive ductal carcinomas and 27% of the intraductal carcinomas showed a positive reaction for B72.3. Ten percent of the lobular neoplasias and 25% of the invasive lobular carcinoma reacted with B72.3. None of the 15 tubular carcinomas or the 15 cases of sclerosing adenosis reacted. One of eight examples of atypical intraductal hyperplasia (12.5%) showed a positive reaction, but none of the nine intraductal hyperplasias reacted with B72.3. The most consistently positive results were observed in cases displaying apocrine metaplasia. A positive reaction was observed in 23 of the 24 cases of apocrine metaplasia (96%) and 17 of 18 cases of apocrine carcinoma (94%). Thus we conclude that B72.3 is neither specific nor sensitive for the detection of malignant breast lesions. However, it does appear to be a valuable marker for the presence of apocrine differentiation, which is not a known precursor of carcinoma.     

Gut-endocrinomas (carcinoids and related endocrine variants) of the breast: an analysis of 310 reported cases

The purpose of this study was to analyze the present status of gut-endocrinomas (carcinoids and related endocrine variants) of the breast, an extremely rare site for primary growth of such neoplasms, and to provide precise and reliable information concerning these neoplasms on varying clinicopathological aspects for investigators engaged in relevant research fields. A total of 310 cases presented in this analysis consisted of 196 carcinoids, 102 typical and 94 atypical, and 114 related endocrine variants; in the last group, the expression of "breast carcinoma with (neuro-) endocrine differentiation" was often used without referring to the term "carcinoid." A statistical evaluation was performed on most occasions based on a comparison among three groups of typical carcinoids, atypical carcinoids and related endocrine variants, or between the former two series of carcinoids and the third series of endocrine carcinomas. Statistically significant differences between the groups of carcinoids and endocrine carcinomas were recognized in terms of average age, tumor size categories of < or = 20 mm and 21-50 mm, rates of metastases, and positive neuron-specific enolase (NSE) immunohistochemistry. Contrary to our expectations no statistically significant difference between these two groups was evident in terms of overall average tumor size, Grimelius argyrophilia for endocrine nature, or postoperative 5-year survival rates in curative resection cases. It seems important to establish more precise diagnostic criteria for "endocrine carcinomas" from the viewpoint of a certain possibility that some of these neoplasms may belong to the atypical carcinoid group.     

Papillary cystic tumor of the pancreas. An analysis of cellular differentiation by electron microscopy and immunohistochemistry

Three cases of clinically benign pancreatic papillary cystic tumors in young female patients were studied by immunohistochemistry and electron microscopy in order to define the cellular nature of this type of neoplasm. Two of the tumors showed focal cytokeratin- and desmoplakin-positivity as evidence of focal epithelial differentiation, while the tumor cells were in all cases positive for vimentin--the intermediate filament protein typical of (but not specific for) mesenchymal cells. Electron microscopy showed some cell-cell junctions, but there was no evidence of acinar or islet cell differentiation. The tumors were at least focally positive for neuron-specific enolase, and small clusters of polypeptide hormone immunoreactive cells were present in all cases (glucagon 3/3, somatostatin 2/3, insulin 2/3). However, the tumors were negative for synaptophysin and neurofilament proteins, unlike most islet cell tumors. Trypsin and chymotrypsin immunoreactivity was found in all tumors, but because many nonpancreatic carcinomas were also positive, we doubt whether these two enzyme proteins can act as specific markers for pancreatic acinar cell differentiation. Two of the tumors that were studied immunohistochemically for the presence of nuclear estrogen receptors, were negative. Therefore no proof of the suggested hormone dependence of this tumor could be obtained. We conclude that papillary cystic tumor is a neoplasm of primitive pancreatic epithelial cells, that may exhibit focal endocrine cell differentiation.     

Immunohistochemical demonstration of tumor-associated antigens in prostatic carcinomas of various histological differentiations

Prostate acid phosphatase (PAP), prostate-specific antigen (PSA), carcinoembryonic antigen (CEA) and keratin were determined immunohistochemically in paraffin sections from 64 prostatic carcinomas fixed in formalin according to the conventional method. The results obtained with PSA led to the correct diagnosis of prostatic carcinoma in 90.7% of the cases. 80.3% of the diagnoses obtained with PAP were correct. The intensity of the staining of the marker decreased with increasing differentiation. 3 utricular carcinomas were positive for PAP and PSA. CEA and keratin may be considered unspecific tumor markers only. However, metaplastic squamous epithelium from poorly differentiated carcinomas was always positive for keratin. PAP and PSA are also suitable for differentiating between tumors of prostatic and nonprostatic origin and could thus be successfully used to determine immunohistochemically the histogenesis of 15 invasive, poorly differentiated carcinomas of the prostate and bladder. PSA again proved to be a more specific epithelial marker than PAP.     

Immunohistochemical features of claudin-low intrinsic subtype in metaplastic breast carcinomas

PurposeThe claudin-low molecular subtype of breast cancer includes triple negative invasive carcinomas, with a high frequency of metaplastic and medullary features. The aim of this study was to evaluate the immunohistochemistry expression of claudins in a series of metaplastic breast carcinomas. We also assessed other claudin-low features, such as the cancer stem cell-like and epithelial-to-mesenchymal transition phenotypes.ResultsThe majority of the cases showed weak or negative staining for membrane claudins expression. We found 76.9% (10/13) low expressing cases for claudin-1, 84.6% (11/13) for claudin-3 and claudin-4, and 92.3% (12/13) for claudin-7. Regarding the cancer stem cell marker ALDH1, 30.8% (4/13) showed positive staining. We also showed that the majority of the cases presented a CD44⁺CD24^?/low phenotype, positivity for vimentin and lack of E-cadherin expression. Interestingly, these claudin-low molecular features were specific of the mesenchymal component of metaplastic breast carcinomas, since its frequency was very low in other breast cancer molecular subtypes, as luminal, HER2-overexpressing and non-metaplastic triple negative tumors.ConclusionsThe negative/low expression of claudins and E-cadherin, high levels of vimentin, and the breast cancer stem cell phenotype suggests that metaplastic breast carcinomas have similar features to the ones included in the claudin-low molecular subtype, specially their mesenchymal components.     

Immunological studies on the occurrence and properties of chromogranin A and B and secretogranin II in endocrine tumors

We investigated a variety of endocrine tumors for the presence of chromogranins A and B and secretogranin II. These antigens were identified by one- and two-dimensional immunoblotting and in some cases by immunohistochemistry. An antigen corresponding in electrophoretic behavior to adrenal chromogranin A was present in all types of tumors, including insulinomas, oat cell carcinomas, and Merkel cell tumors of the skin. Chromogranin B had a much more limited distribution. This antigen could not be detected in parathyroid adenomas, oat cell carcinomas, or Merkel cell tumors, either by immunoblotting and immunohistochemistry. The occurrence of secretogranin II was similar to that of chromogranin B, with the exception of a positive reaction in Merkel cell tumors. In benign pheochromocytomas, all three antigens were found consistently; whereas in two of three malignant pheochromocytomas, chromogranin B was absent. Our study establishes that in most cases chromogranins and secretogranin in tumors are identical to the adrenal antigens, but that these antigens are not always stored together. Chromogranin A is the most widely distributed marker for endocrine tumors.     

Biopathological significance of single cell DNA aneuploidy measured by static cytometry in breast cancer

DNA ploidy image analysis in breast carcinomas has occasionally revealed cases with a diploid DNA content but with a single hypertetraploid element, the so-called single cell aneuploidy (SCA). To identify the biologic significance of this little known phenomenon, we selected 40 cases with SCA from a series of 599 consecutive operable breast carcinomas. The clinical, pathological and biological characteristics of SCA cases were compared with those of a control group of 40 pure diploid breast carcinomas. Hormonal receptor status, proliferative indexes (Ki-67) and p53 overexpression were determined immunohistochemically and quantitatively evaluated by image analysis. The overexpression of c-erbB-2 was determined semiquantitatively. SCA was observed in 6.6% of cases (40 of 599) and in 17% of otherwise diploid cases (40 of 236). Breast cancers with SCA occur in younger women (mean age 54.75 y vs 61.12 y, P<0.05), are smaller (mean diameter 20.00 vs 21.62 mm), less differentiated (percentage of G3 cases 13.2 vs 2.9), more frequently hormone independent (ER positivity 70.0 vs 77.5%; PgR positivity 57.5 vs 77.5%) and have a greater cell proliferative activity (mean S-phase: 4.6 vs 2.8, P<0.05), (percentage of Ki-67 immunostaining: 24.1 vs 19.7%). There is also more overexpression of c-erbB-2 and P53, particularly in pT1 cases in which the percentage of c-erbB-2 positive cells is 54 vs 32 (P value is not significant) and the percentage of p53 is 29 vs 4 (P<0.05). According to these results SCA may be a reliable marker of genetic instability and of greater biologic aggressiveness. Image cytometry of DNA content may be a cost effective means of identifying breast cancer patients with an increased risk of tumour recurrences despite otherwise favourable prognostic parameters.     

荧光定量聚合酶链反应检测乳腺癌外周血微小转移

目的：探讨应用荧光定量聚合酶链反应（FQ－PCR）扩增乳腺组织特异性基因hMAM mRNA作为检测乳腺癌血行微小转移方法的可能性。方法：利用逆转录RT－PCR检测hMAM mRNA在乳腺癌细胞系SKBR3的表达，将FQ－PCR与普通PCR的敏感性进行比较，并利用FQ－PCR对乳腺癌等不同病种患者101例及健康志愿者31例的外周血进行检测，分析hMAM mRNA表达与乳腺癌临床特点之间的关系。结果：普通巢式PCR扩增hMAM mRNA在10^6个白细胞中可检测出1个SKBR3细胞，而巢式FQ－PCR可在10^7个白细胞中可检测出1个SKBR3细胞，63例乳腺癌患者外周血中19例hMAM mRNA阳性（阳性率30％），随肿瘤分期进展阳性率增高，其他病种患者外周血中均阴性，而31例健康献血员中有1例阳性，结论：巢式FQ－PCR是检测乳腺癌微小转移的敏感方法。     

Invasive ductal carcinomas of the breast showing partial reversed cell polarity are associated with lymphatic tumor spread and may represent part of a spectrum of invasive micropapillary carcinoma

Invasive micropapillary carcinomas (IMPC) of the breast are aggressive tumors frequently associated with lymphatic invasion and nodal metastasis even when micropapillary (MP) differentiation is very focal within the tumors. We have noticed that some breast carcinomas showing lymphatic spread but lacking histologic features of IMPC have occasional tumor cell clusters reminiscent of those of IMPC without the characteristic prominent retraction artifact. To study the clinicopathologic significance of such features, we prospectively selected 1323 invasive ductal carcinomas and determined the presence and extent of MP differentiation and retraction artifact in the tumors. One representative tumor block per case was used for immunostaining for epithelial membrane antigen (EMA). Partial reverse cell polarity (PRCP) was defined as prominent linear EMA reactivity on at least part of the periphery of tumor cell clusters usually associated with decreased cytoplasmic staining. The clinicopathologic features of carcinomas with PRCP were compared with IMPC and invasive ductal (no special type) carcinomas without this feature. Of the 1323 cases, 96 (7.3%) and 92 (7.0%) showed MP features and the presence of PRCP, respectively. We found that the presence of both PRCP and MP features were strongly associated with decreased cytoplasmic EMA immunoreactivity and the presence of lymphatic invasion and nodal metastasis, even if such features were present only very focally. Our results suggest that breast carcinomas with PRCP may have the same implication as MP differentiation and these tumors may represent part of a spectrum of IMPC. Complete or partial reversal of cell polarity may play a significant role in lymphatic tumor spread.     

乳腺癌针吸细胞学激素受体的测定及临床意义研究

目的探讨乳腺癌针吸细胞学激素受体检测的临床意义。方法应用单克隆抗体免疫组化法对42例乳腺癌患者的针吸细胞学涂片与组织切片检查结果对照。结果针吸细胞学涂片与其石蜡切片雌激素受体(ER)、孕激素受体(PR)检测的总符合率为83.3%、80.95%,二者差异无统计学意义。结论乳腺癌针吸细胞涂片检测激素受体结果与组织切片同样可靠。这种方法简便易行,安全性好,对不适合手术的患者的治疗方案选择具有重要的意义。     

Detection of estrogen receptor in paraffin-embedded sections of breast carcinoma by immunohistochemistry and in situ hybridization.

Biopsy specimens of small breast carcinomas are often insufficient for both diagnosis and the biochemical determination of estrogen receptor (ER) protein. Recent reports from various laboratories have shown the utility of immunohistochemical detection of ER protein in paraffin-embedded tissue sections. We used immunohistochemical (IHC) staining with the Abbott ER antibody (H222) and in situ hybridization (ISH) analysis with a 35S-labeled and a biotinylated oligonucleotide probe to detect ER protein and messenger RNA (mRNA) in tissue sections of 53 breast carcinomas. The dextran-coated charcoal (DCC) assay of these same cases revealed positive receptor levels in 31 of 53 cases, whereas the IHC method was positive in 33 of 53 cases. ISH for detection of ER mRNA was more sensitive than IHC or the biochemical assay for estrogen binding proteins, as the isotopic probe detected ER mRNA in 47 of 53 cases, whereas the biotinylated probe detected ER mRNA in 46 of 53 cases. These results indicate that ER protein can be readily detected in enzyme-treated paraffin tissue sections and that the IHC detection of ER protein correlates highly with the DCC assay. ISH with isotopic and biotinylated probes detects ER mRNA in most cases found to be positive for ER protein and also in many cases without detectable ER protein. Although detection of ER protein in paraffin sections correlates highly with the biochemical assay in this report and in other reported studies, the clinical significance of increased sensitivity by ISH is unknown and must await clinical correlative follow-up studies.     

Mammary endocrine ductal carcinoma in situ: a case report

Endocrine differentiation represents a pathway of neoplastic development available to a range of breast cancers. This pattern occurs in tumors with different morphological appearances as ductal carcinoma in situ (DCIS), mucinous carcinoma, a variant of lobular carcinoma, and low-grade invasive ductal carcinoma. Endocrine ductal carcinoma in situ is an uncommon entity. It occurs in older women with a mean age of 70 years. Histologically it shows expansile intraductal growth forming solid sheets and festoons transversed by delicate fibrovascular septa. Conventional microscopy permits the diagnosis in most cases. Specialized techniques such as immunohistochemistry and electron microscopy can serve as the basis of diagnosis in the absence of the appropriate morphological features. We present a 68-year-old female with a 1.5-cm firm mobile nodule of the left breast. Mammography and ultrasounds showed a 15 x 15-mm circumscribed solid lobulated nodule. The mass was excised and pathology was positive for endocrine DCIS. Although endocrine DCIS has a biologic marker profile similar to that of well-differentiated or noncomedo DCIS it may constitute a different histogenetic pathway of carcinogenesis in the breast. The tumor may exhibit the invasive characteristics of a neuroendocrine neoplasm. Larger studies and longer follow-up are needed for the determination of the clinical behavior.     

The mucin profile of noninvasive and invasive mucinous cystic neoplasms of the pancreas

Recently, it was shown that ductal adenocarcinomas and intraductal papillary-mucinous neoplasms of the pancreas differ in their expression of the mucin markers MUC1 and MUC2 while both tumors express MUC5AC. It is not known whether mucinous cystic neoplasms of the pancreas have their own mucin profile. To clarify this issue, 22 mucinous cystic neoplasms were examined immunohistologically for their expression of MUC1, MUC2, MUC5AC, and MUC6 and also for the protein products of the tumor suppressor genes p53 and DPC4 and the mismatch repair genes. Noninvasive mucinous cystic neoplasms, regardless of the degree of cellular atypia, were all positive for MUC5AC and negative for MUC1, with the exception of the cyst-lining epithelium of a single case with eosinophilic cytology (case no. 16). Only in cases with an invasive component was MUC1 expression observed. MUC2 expression was restricted to goblet cells scattered within the epithelium of the mucinous cystic neoplasms and was often accompanied by endocrine cells, a further indication of intestinal differentiation. DPC4 expression was maintained in all tumors, except for three invasive carcinomas. p53 nuclear reactivity was found in one borderline tumor and four invasive mucinous cystic carcinomas. The results suggest that the epithelium of noninvasive mucinous cystic neoplasms does not differ in its expression of MUC5AC from ductal adenocarcinomas, intraductal papillary-mucinous neoplasms, and metaplastic pancreatic duct epithelium. The fact that noninvasive mucinous cystic neoplasms lack MUC1 expression (except for an eosinophilic variant) but express it when they become invasive might be used as a marker indicating the step of progression from noninvasiveness to invasiveness.     

Increased endocrine cells in treated rectal adenocarcinomas: a possible reflection of endocrine differentiation in tumor cells induced by chemotherapy and radiotherapy

The presence of focal endocrine cells in colorectal adenocarcinoma is a relatively common phenomenon. However, endocrine differentiation in treated adenocarcinomas of the gastrointestinal tract has received little attention. We noted striking numbers of cells with endocrine morphology and phenotype in the residual tumor of six randomly encountered cases of rectal adenocarcinoma that were subjected to neoadjuvant therapy. All six cases had a substantial treatment response (> or =50%). To validate our initial observation and to explore its clinicopathologic significance, further morphologic and immunohistochemical studies were performed on 53 cases of rectal adenocarcinomas treated with preoperative radiation with (33 cases) or without (20 cases) chemotherapy. Pretreatment biopsies from 20 of the 53 cases and 79 resection specimens of rectal adenocarcinoma that received no neoadjuvant therapy were used as controls. Chromogranin positivity was identified in the posttreatment resection specimens in 36 of the 53 study cases (67.9%). Twenty of the 36 showed positive staining in > or =20% of the residual tumor cells. The chromogranin-positive cells in these cases often formed cords or nests. On hematoxylin and eosin sections these cells had markedly eosinophilic cytoplasm and round and uniform or sometimes pleomorphic nuclei with an often dense chromatin pattern. The proportion of chromogranin-positive cells was significantly associated with the extent of treatment response (p = 0.0005). Tumors treated with both chemotherapy and radiotherapy were more likely to have abundant chromogranin-positive cells compared with tumors treated with radiotherapy alone (p = 0.0004). In contrast, only 30% of the pretreatment biopsies and 17.7% of the control resection specimens of untreated rectal carcinomas showed chromogranin-positive cells, predominantly arranged as scattered individual positive cells, constituting <10% of the tumor. No significant correlation was observed between pretreatment and posttreatment specimens with regard to chromogranin positivity (p = 1.0). Ten of 15 patients (66.7%) whose resection specimens showed positive chromogranin staining failed to demonstrate any chromogranin positivity in their pretreatment biopsy specimens. In addition, groups or nests of chromogranin-positive cells noted in posttreatment specimens showed a very low Ki67 labeling index (<5%) but showed a frequency of abnormal p53 protein expression comparable with that observed in tumor foci resembling conventional adenocarcinoma (66.7% vs 62.5%). Our findings demonstrate that there is an increased frequency and density of cells with an endocrine phenotype in rectal adenocarcinomas that were subjected to neoadjuvant therapy and that the extent of endocrine cells appears proportional to the degree of treatment response. The possible mechanism for the increased endocrine cells in treated rectal adenocarcinomas may be related to induction of endocrine differentiation in tumor cells by cytotoxic insult.     

Lack of peptide YY immunoreactivity in adenomatous colonic polyps: evidence in favor of an adenoma-carcinoma sequence

The aim of endoscopic polypectomy is to prevent colorectal cancer, as it is assumed that most, if not all, large bowel cancers are derived from adenomatous polyps. While it is now recognized that colonic endocrine cells, like other mucosal epithelial cells, have an endodermal origin, they are relatively sparse components of large bowel tumors. Peptide YY (PYY) is the most abundant endocrine regulatory peptide localized to the distal bowel. Endocrine cells, like the other cells of the mucosal epithelia, are derived from a common stem cell in the base of the crypts. The presence of endocrine peptides may thus be viewed as a marker for cellular differentiation in the gut. PYY was therefore measured in colonic carcinomas and adenomatous polyps, as its absence would be evidence in favor of genetic alterations in epithelial stem cell maturation. PYY concentrations in extracts of surgically removed colonic carcinomas (n = 22) from all regions were very low compared with those of adjacent normal bowel. Similarly, PYY concentrations in extracts of polyps (n = 39) obtained during endoscopic polypectomy were also very low when compared with those of adjacent normal mucosa. These varied between 1 and 11% of the normal epithelial content, depending upon the region. Low PYY levels appeared to reflect the malignant potential of these lesions: highest in tubular polyps, lower in villous polyps, and lowest in carcinomas. The very low concentrations of PYY in adenomatous polyps, like those of colonic cancer, are consistent with epithelial dysplasia and the incomplete formation of mucosal endocrine cells. These findings support the hypothesis of an adenoma to carcinoma sequence in colonic cancer.     

Expression of WT1, CA 125, and GCDFP-15 as useful markers in the differential diagnosis of primary ovarian carcinomas versus metastatic breast cancer to the ovary

Metastatic breast carcinoma to the ovary is sometimes difficult to differentiate from primary ovarian carcinoma. This problem is often encountered in breast carcinoma patients who develop adnexal masses. ER and PR can be positive in a high percentage of breast and ovarian carcinomas, and therefore cannot be used in the differential diagnosis of these entities. WT1 and CA125 have been identified as possible markers for ovarian cancer. However, no studies have been done that specifically compare the immunophenotype of breast carcinoma metastatic to ovary with that of primary ovarian cancer. Thirty-nine cases of metastatic breast carcinoma to the ovary, 36 primary breast carcinomas, and 42 primary ovarian carcinomas were examined immunohistochemically for the expression of WT1, CA125, carcinoembryonic antigen, MUC2, MUC1, and GCDFP. The percentage of cells stained and the intensity of staining were recorded. Thirty-two ovarian carcinomas (76%) were positive for WT1, including 31 of 33 (94%) serous carcinomas. Most of them had strong and diffuse staining. None of the breast cancers either primary or metastatic to the ovary expressed WT1. Thirty-eight (90%) ovarian carcinomas were positive for CA125, most of them with strong and diffuse staining. Most breast carcinomas were negative for CA125, with only 6 (16%) of the primary ones and 5 (12%) of the metastatic showing weak and focal positivity. All ovarian carcinomas were negative for GCDFP. Five primary breast cancers (14%) and 17 (43%) metastatic to the ovary were positive for GCDFP. Nine (21%) ovarian carcinomas, 8 (22%) primary breast carcinomas, and 13 (33%) metastatic to the ovary were positive for carcinoembryonic antigen. Almost all tumors examined were positive for MUC1 (100% ovarian carcinomas, 100% primary breast carcinomas, and 95% metastatic breast carcinomas to ovary). MUC2 was positive in 10 (24%) ovarian carcinomas, 3 (8%) primary breast cancers, and 12 (30%) metastases to the ovary. The presence of immunoreactivity for WT1 and CA125 in a carcinoma involving ovary strongly favors a primary lesion. Most ovarian carcinomas are positive for both markers, whereas the majority of metastatic breast carcinomas to the ovary are negative. GCDFP can be complementary in this differential diagnosis.     

Calcium oxalate crystals in the breast. Pathology and significance

Deposits of birefringent calcium oxalate crystals in the breast constitute a mammographically detectable but often histologically overlooked form of calcification. Unstained by routine dyes, these deposits are important as a cause of discrepant radiographic and microscopic biopsy findings. To elucidate the pathologic changes that give rise to these crystals and the possible significance of these deposits in the breast, we retrospectively studied 119 breast biopsies from 100 women. By polarized light microscopy, we identified 16 cases with calcium oxalate deposits from this group. The crystals were typically within benign cysts or terminal ductules exhibiting apocrine differentiation by conventional morphologic criteria or by immunoreactivity to monoclonal antibodies against gross cystic disease fluid protein of 1,500 MW (anti-GCDFP-15). The lesions harboring the crystals were papillary or cystic apocrine metaplasia in 14 cases and simple apocrine metaplasia in two cases. These lesions were associated with separate foci of lobular carcinoma in situ in three cases and with other proliferative lesions regarded as risk markers for invasive carcinoma in six other cases. Paradoxically, the crystals were rarely seen in association with infiltrating carcinomas. Our findings support the concept that calcium oxalate deposits are a secretory form of calcification. The association with lobular carcinoma in situ and the rarity of the crystals in invasive carcinomas are in accord with previous observations. We found polarized light microscopy indispensable for the demonstration of these deposits in hematoxylin-eosin-stained sections.