Expression of apocrine differentiation markers in neuroendocrine breast carcinomas of aged women.

Neuroendocrine (NE) breast carcinomas are a rare entity in young women; however, their frequency increases in aged patients. The present work demonstrates that NE breast carcinomas in elderly women can also express an apocrine immunophenotype and analyzes the histological and clinical aspects of such differentiation. A selected series of 50 NE tumors (positive for NE markers in >/=50% of the cells) was tested for the immunocytochemical expression of gross cystic disease fluid protein-15 (GCDFP-15). The results demonstrated that about 50% of moderately (G2) and well-differentiated (G1) NE breast carcinomas (mucinous, solid papillary, and solid cohesive histotypes) coexpressed the apocrine marker. In these cases, specific mRNA for GCDFP-15 (PIP) and for chromogranin A (ChA) was demonstrated using in situ hybridization (ISH). Carcinomas of the alveolar subtype (G2) and poorly differentiated carcinomas (G3), including one case of atypical carcinoid, were pure NE carcinomas, devoid of apocrine differentiation. The steroid receptor status of these lesions was evaluated to test a possible involvement of androgen receptors in apocrine differentiation. We demonstrated that the level of AR and the mean age of patients at diagnosis were significantly higher in apocrine than in nonapocrine differentiated tumors. The histological grade and the expression of estrogen receptor (ER) significantly influenced the prognosis of these NE carcinomas, either pure or NE-apocrine differentiated. The most original result of our study is therefore the demonstration of a possible divergent apocrine differentiation of NE breast carcinomas that might be regulated by the activation of androgen receptors in elder patients. In addition, the possibility for using Chs or GCDFP-15 serum values in the follow-up of these patients, as demonstrated in two cases of the present series, can justify the immunophenotyping of the tumors.     

Apocrine carcinoma of the breast. A morphologic and immunocytochemical study.

The mode of recognition and hence the frequency of apocrine differentiation in breast carcinomas, assessed on purely morphologic grounds, remains uncertain. One hundred consecutive cases of breast carcinoma were studied in order to establish the incidence of this type of tumor. With the use of an immunocytochemical method for the detection of GCDFP-15, a protein present in apocrine epithelium and in the fluid of tension cyst of the breast, the presence of apocrine differentiation was confirmed in 4 cases initially diagnosed as apocrine carcinomas on histologic grounds. Eight additional cases contained immunoreactive cells: 1 contained 10% of positive cells scattered throughout the tumor, and the other 7 cases were only focally positive. In 4 of these latter cases positive staining was confined to the in situ component. The ultrastructural findings in 2 cases of apocrine carcinoma are discussed in order to link the morphologic features for recognizing this tumor type and the presence of the antigenic apocrine marker.     

Expression of the PIP/GCDFP-15 gene and survival in breast cancer

Expression of the PIP/GCDFP-15 gene was determined by measuring PIP/GCDFP-15-mRNA in breast carcinomas of 91 patients. The patients were followed-up for an average of 47 months after initial diagnosis and treatment of the disease. There were no deaths in the group of 14 patients with tumours of high PIP/GCDFP-15-mRNA levels, while 16 of 77 patients of the group with low PIP/GCDFP-15-mRNA tumour levels died. A similar advantage for high PIP/GCDFP-mRNA expression was observed with regard to disease free survival.     

Comparative study of monoclonal antibody B72.3 and gross cystic disease fluid protein-15 as markers of apocrine carcinoma of the breast

Gross cystic disease fluid protein-15 (GCDFP-15) is a commonly used apocrine marker; however, its expression was recently found to decrease in infiltrating, larger, or metastasizing apocrine carcinomas of the breast. In the breast, monoclonal antibody (MAb) B72.3 has been reported to be useful as an apocrine marker although it is used for that purpose much less frequently than GCDFP-15. In the search for a more consistent apocrine marker, immunoreactivity for MAb B72.3 was examined in apocrine carcinomas at different stages and compared with GCDFP-15. 47 of 51 apocrine carcinomas (92%) and 9 of 62 ordinary carcinomas (15%) were MAb B72.3 positive, while 39 of 51 apocrine carcinomas (76%) and 13 of 62 ordinary carcinomas (21%) were GCDFP-15 positive. Thus, both sensitivity and specificity were higher for MAb B72.3. Furthermore, unlike GCDFP-15, MAb B72.3 exhibited positivity irrespective of infiltrating status, tumor size, or metastatic status. There was no correlation between MAb B72.3-immunoreactivity and GCDFP-15-expression. The combined usage of MAb B72.3 with GCDFP-15 was useful to confirm the diagnosis of apocrine carcinoma, especially for advanced tumors, with only two cases being negative for both MAb B72.3 and GCDFP-15. Whether these two cases should be differentiated from ordinary apocrine carcinomas remains to be investigated.     

Expression of the PIP/GCDFP-15 gene and survival in breast cancer

pExpression of the PIP/GCDFP-15 gene was determined by measuring PIP/GCDFP-15-mRNA in breast carcinomas of 91 patients. The patients were followed-up for an average of 47 months after initial diagnosis and treatment of the disease. There were no deaths in the group of 14 patients with tumours of high PIP/GCDFP-15-mRNA levels, while 16 of 77 patients of the group with low PIP/GCDFP-15-mRNA tumour levels died. A similar advantage for high PIP/GCDFP-mRNA expression was observed with regard to disease free survival.     

Infiltrating lobular carcinoma of the breast with histiocytoid features: three cases

Histiocytoid carcinoma of the breast, a cellular variant of invasive breast cancer, is mainly found among infiltrating lobular carcinomas (ILC). It can be easily confused with benign conditions or other mammary tumors also composed of cells with a pink granular to foamy cytoplasm and an eccentric nucleus. We report 3 cases of histiocytoid ILC. Our aim is to discuss recent immunocytochemical data that could suggest a special type of apocrine differentiation of tumor cells, including a diffuse immunoreactivity for GCDFP-15 (Gross Cystic Disease Fluid Protein 15) and a predominant expression of androgen receptor, and to describe the features useful for the differential diagnosis.     

Monoclonal antibody B72.3 immunostaining of breast carcinoma. Patterns of staining and relationship to mucin content and GCDFP-15 reactivity.

Around 80% of breast carcinomas express the tumor-associated glycoprotein-72, as demonstrated by positive immunostaining with the monoclonal antibody B72.3. We have investigated the pattern of B72.3 immunostaining in 88 breast carcinomas of different types, with the use of an immunoperoxidase technique. As tumor-associated glycoprotein-72 has mucinlike properties and is usually present in cells that show apocrine differentiation, we have also compared the results of B72.3 immunostaining in these tumors with the staining results for mucin and GCDFP-15, which is another antibody that recognizes apocrine differentiation. A variable degree of B72.3 immunostaining was seen in 60 cases (68%). The staining patterns varied with the histological type and sometimes within the same type. A significant relationship was demonstrated between B72.3 positivity and the presence of acidic mucin in the tumors, but not with their staining for GCDFP-15. The extent, distribution, and pattern of immunostaining for B72.3 varies in different types of breast carcinoma; this fact has to be taken into consideration if radiolabeled B72.3 monoclonal antibodies are going to be used for therapeutic purposes.     

Apocrine epithelium of the breast: does it result from metaplasia?

 Benign and malignant breast lesions may show an apocrine epithelium considered to be the result of metaplasia. In an attempt to clarify the histogenesis of the breast apocrine epithelium we searched for the presence of apocrine cells or cells with apocrine differentiation during human breast development. We analysed 10 autopsy specimens of female breasts from fetuses between 28 and 40 weeks of gestational age and tissue from 6 normal breasts, obtained after breast reduction in nulliparous young women between 22 and 28 years of age. Formalin-fixed, paraffin-embedded sections were stained with haematoxylin-eosin, PAS-diastase and a monoclonal antibody (BRST-2) anti-GCDFP-15, which is a specific apocrine marker. A 40-week fetal breast was analysed by electron microscopy. No cells with histological and ultrastructural apocrine features were found in the ducts of fetal breasts. All fetal breasts showed some ducts with sparse GCDFP-15-immunoreactive cells; the number of these cells increased with gestational age. PAS-diastase was negative. No cells with apocrine morphology were found in ducts and lobules of normal adult breasts. Scattered GCDFP-15-positive luminal epithelial cells and rare PAS-diastase-positive cells were observed in some lobules of all adult breasts. Cells with biochemical characteristics (GCDFP-15 expression) of apocrine differentiation are evident during human fetal breast development and persist in adult mammary glands. Unknown stimuli may induce these cells to take on an apocrine morphology. Apocrine epithelium of the breast may be a normal process of differentiation rather than metaplasia. We suggest the term ”apocrine differentiation precursor cells” for GCDFP-15-positive breast epithelial cells with no apocrine morphology. Received: 14 February 1997 / Accepted: 12 April 1997     

Immunohistochemical localization of gross cystic disease fluid protein-15, -24 and -44 in ductal carcinoma in situ of the breast: relationship to the degree of differentiation

AIMS: Three major proteins present in breast gross cystic disease fluid and expressed by the cyst lining apocrine epithelium are gross cystic disease fluid protein-15 (GCDFP-15), apolipoprotein-D (APO-D; GCDFP-24) and zinc alpha2-glycoprotein (ZnGP; GCDFP-44). The aim of this study was to investigate the expression of these proteins in ductal carcinoma in situ (DCIS) of the breast and to relate their expression with the degree of differentiation of DCIS. METHODS AND RESULTS: An immunohistochemical study of these proteins was performed in 57 cases of DCIS and nine cases of morphologically apocrine DCIS. Positivity was seen in 24/57 (42.1%) cases with anti-GCDFP-15, 20/57 (35.1%) cases with anti-GCDFP-24 and 22/57 (38.6%) cases with anti-GCDFP-44. GCDFP-15 positivity was noted in 5/13 (38.5%) of the well-differentiated, 11/19 (57.9%) intermediately differentiated and 8/25 (32.0%) of the poorly differentiated cases (P=0.217). GCDFP-24 positivity was seen in 3/13 (23.0%) well-differentiated, 9/19 (47.4%) intermediately differentiated and 8/25 (32.0%) poorly differentiated cases (P=0.336). GCDFP-44 was detected in 5/13 (38.5%) of well-differentiated cases, 11/19 (57.9%) intermediately differentiated and 6/25 (24.0%) poorly differentiated cases (P=0.074). In the nine cases of apocrine DCIS, GCDFP-15 positivity was detected in seven (77.8%), while five (55.6%) and six (66.7%) cases were positive for GCDFP-24 and GCDFP-44, respectively. CONCLUSIONS: The results indicate that there is no significant association between the expression of the studied proteins and the degree of differentiation of DCIS of the breast. Moreover, some morphologically apocrine DCIS cases appear to lose expression of these proteins.     

Immunohistochemistry of a gross cystic disease fluid protein (GCDFP-15) of the breast. A marker of apocrine epithelium and breast carcinomas with apocrine features.

Gross cystic disease fluid is a pathologic secretion from breast composed of several glycoproteins, including a unique 15,000-dalton monomer protein, GCDFP-15. By the immunoperoxidase technique, GCDFP-15 was localized in the apocrine metaplastic epithelium lining breast cysts and in apocrine glands in the axilla, vulva, eyelid, and ear canal. In normal breast tissue, a few individual epithelial cells within lobules and small ducts were focally positive for GCDFP-15. Fourteen of 30 breast carcinomas stained positively for GCDFP-15. Of 16 carcinomas with apocrine features, 12 stained positively. Benign and malignant lesions from other tissues, including lung, colon, ovary, endometrium, stomach, prostate, liver, esophagus, and kidney, revealed no immunoreactivity. The only cells of "non-apocrine" tissues that contained GCDFP-15 were serous cells of the submandibular salivary gland, submucosal glands of the bronchi, and accessory lacrimal glands. Phylogenetically, these tissues have biologic features in common with apocrine glands. This report is the first to characterize GCDFP-15 as a specific tissue marker of apocrine epithelium.     

The ultrastructural localization of gross cystic disease fluid protein (GCDFP-15) in breast epithelium.

GCDFP-15 is a major constituent protein of 15,000-dalton monomer size present in breast gross cystic disease fluid. Immunoperoxidase staining of GCDFP-15 has shown the protein to be present in normal apocrine epithelium, metaplastic apocrine epithelium of the breast, and breast carcinomas with apocrine features. To delineate ultrastructurally the localization of GCDFP-15 in benign breast epithelium, a low-temperature embedding colloidal gold technique was used. Metaplastic apocrine epithelium of the breast showed GCDFP-15 to be localized in Golgi vesicles and cytoplasmic granules. At the cell apices these granules were contained in vacuoles and appeared to be released by exocytosis. There was labeling of cyst fluid within microcyst lumens. This report is the first to ultrastructurally characterize this protein and its mode of secretion.     

Immunohistochemical analysis of pleomorphic lobular carcinoma: higher expression of p53 and chromogranin and lower expression of ER and PgR

AIMS: Pleomorphic lobular carcinoma of the breast is a histological variant of infiltrating lobular carcinoma with a poor prognosis. The aim of this study is to investigate the immunohistochemical profile of this distinctive breast carcinoma in comparison with the classical type. The expression of cytokeratin, epithelial membrane antigen, gross cystic disease fluid protein-15, chromogranin, oestrogen and progesterone receptors and p53 oncoprotein was investigated to examine whether the expression of these markers correlates with the aggressiveness of this variant. METHODS AND RESULTS: Sections from 10 cases of pleomorphic lobular carcinomas were reviewed and examined for the expression of cytokeratin of high and low molecular weight, epithelial membrane antigen (EMA), gross cystic disease fluid protein-15 (GCDFP-15), chromogranin, oestrogen (ER) and progesterone receptors (PgR), and p53 oncoprotein. Immunohistochemical staining was performed on paraffin wax embedded sections. Ten cases of classical lobular carcinomas were used for comparison. A semiquantitative count of the percentage of positive tumour cells was recorded. Pleomorphic lobular carcinomas have most of the characteristic histological features of the classical type but have nuclear anaplasia and abundant granular cytoplasm. Clinically they exhibited poor prognosis and a high frequency of nodal metastases. All of the pleomorphic lobular carcinomas expressed low and high molecular weight keratin, EMA, and GCDFP-15, eight cases expressed nuclear p53 at a range between 10% and 45%. All cases expressed chromogranin (3-5%). ER and PgR were weakly positive in two cases and negative in eight cases. Classical infiltrating lobular carcinomas were all positive for cytokeratin, EMA, ER and PgR and negative for GCDFP-15. Only five cases of classical lobular carcinoma expressed p53 positivity with up to 5% nuclear staining while chromogranin showed less expression (1-2%). CONCLUSION: Pleomorphic lobular carcinoma exhibits distinct cellular features with apocrine differentiation, higher expression of chromogranin and p53 protein and lower ER and PgR in comparison with classical lobular carcinomas. Determination of p53 overexpression and reduced or absent expression of ER and PgR may help predict the behaviour of this variant of lobular carcinoma.     

Immunohistochemical comparison between GCDFP-15 and estrogen and progesterone receptors in the diagnosis of metastatic carcinoma of the breast

Background: in the workup of tumors of unknown primary origin in women, a frequent consideration is breast carcinoma, because it is common and may initially present as metastasis. Objective: describe and compare the immunohistochemical profile of hormonal receptors (estrogen receptor and progesterone receptor) and GCDFP-15 in lymph node metastatic breast carcinoma according the histological grade. Methods: retrospective study analyzing 30 patients with identified primary breast cancer and lymph node metastasis. The cases were divided in three groups: grade I (well differentiated), grade II (moderately differentiated) and grade III (poorly differentiated). We used three antibodies (estrogen receptor, progesterone receptor and GCDFP-15) in the lymph node and compare the expression according the histological grade. Results: in metastatic lymph node from grade I breast carcinomas the hormone receptors were 100% positive and GCDFP-15 was 80% positive. In grade II, estrogen receptor and progesterone receptor were positive in 90 and 40% respectively, and GCDFP-15 was positive in 80%. In grade III, estrogen receptor and progesterone receptor were positive in 30 and 50% respectively, and GCDFP-15 in 60%. Conclusions: the immunohistochemical expression of hormonal receptors and GCDFP-15 in metastatic breast carcinoma is related to histological grade in the breast.     

E-cadherin immunohistochemical analysis of histiocytoid carcinoma of the breast

Histiocytoid carcinoma is a rare type of invasive breast carcinoma. It has been considered to be a variant of lobular carcinoma, a variant of apocrine ductal carcinoma, and an apocrine variant of lobular carcinoma and to resemble lipid-rich carcinoma. In attempts to elucidate its histogenesis, investigators have used mucin and oil red O histochemical analysis and GCDFP-15 immunostaining. E-cadherin is a relatively recent addition to the armamentarium of immunohistochemical markers used for cell differentiation and is a member of a family of transmembrane glycoproteins that has been shown to have a strong correlation with the histologic phenotypes of breast carcinoma. Most ductal carcinomas show diffuse membrane expression of E-cadherin, and lobular carcinomas are characterized by complete lack of membrane staining of E-cadherin. The object of this study was to use E-cadherin immunohistochemical analysis to help clarify the histogenesis of histiocytoid carcinoma. Fourteen cases containing the diagnosis of histiocytoid carcinoma of the breast were identified at M. D. Anderson Cancer Center (Houston, TX) from 1988 to 2001. All cases were rereviewed, histologic features were evaluated, and immunohistochemical staining with E-cadherin and GCDFP-15 was performed. Clinical information was extracted from the patients' medical records. Eleven cases met published histologic criteria for histiocytoid carcinoma. The remaining three cases were apocrine carcinoma. The pattern of tumor infiltration was solid, without secondary lumen formation in all cases of histiocytoid carcinoma. Lobular carcinoma in situ was identified in eight cases, but was absent in three. There was no E-cadherin immunohistochemical staining in eight of the 11 cases of histiocytoid carcinoma (72.7%). GCDFP-15 was immunoreactive in all 10 cases of histiocytoid carcinoma where it was performed. Follow-up data was available for nine of the 11 cases of histiocytoid carcinoma: six patients were alive with disease at 1.5 to 48 months, one patient had died of disease at 60 months, and two patients had no evidence of disease at 32 and 45 months. We conclude that histiocytoid carcinoma has an immunophenotypical profile consistent with both ductal and lobular differentiation. Moreover, the lack of consistent morphologic features, a specific clinical profile, and a distinct immunohistochemical pattern lead us to hypothesize that histiocytoid carcinoma is not a special type of breast cancer.     

Cell-type- and tumour-type-related patterns of bcl-2 reactivity in mesenchymal cells and soft tissue tumours

 GCDFP-15, a glycoprotein identified in the cyst fluid of cystic breast disease, is considered to be a marker of apocrine differentiation. Studies on GCDFP-15 localization in adult normal tissues are lacking, and no information on GCDFP-15 expression during fetal development has been reported. We investigated GCDFP-15 expression in a large series of formalin-fixed, paraffin-embedded normal human adult and fetal tissues using the monoclonal antibody BRST-2. In normal adult tissues GCDFP-15 expression was found in all apocrine, lacrimal, ceruminous and Moll’s glands and in numerous serous cells of the submandibular, sublingual and minor salivary glands. The serous cells of nasal and bronchial glands were also positive; parotid and laryngeal glands showed rare immunoreactive cells. GCDFP-15-positive cells were observed in all cutaneous eccrine glands from different body sites. In fetal tissues immunoreactivity was observed in numerous acinous cells of all tracheal, bronchial and submandibular salivary glands. GCDFP-15 positivity was identified in numerous cells of all axillary sweat glands and in rare cells of some sweat glands of the thorax, abdomen, back, leg and arm. In both apocrine and nonapocrine glands GCDFP-15 was always localized in the secretory component. These data suggest that GCDFP-15 is a glandular differentiation marker associated with apocrine secretion; that it is expressed in glands that have phylogenetic origins in common with apocrine glands (submandibular salivary and submucosal bronchial glands); and that eccrine cutaneous glands express GCDFP-15 and thus might be referred to as mixed apocrine-eccrine glands. GCDFP-15 is expressed during fetal development and may represent a common marker of embryologically linked glandular structures. Received: 22 May 1997 / Accepted: 15 September 1997     

Gross cystic disease fluid protein-15 in salivary gland tumors

Gross cystic disease fluid protein-15 (GCDFP-15) is a 15-kd glycoprotein that is expressed by normal apocrine epithelia and in a majority of breast carcinomas. However, recent studies have demonstrated that this substance is also present in tumors of the salivary glands, sweat glands, and prostate gland. To determine whether the expression of CGDFP-15 might aid in the differential diagnosis of salivary gland lesions, the anti-GCDFP-15 monoclonal antibody D6 was applied to paraffin sections of 133 such neoplasms. Benign tumors (76% reactive) were more often labeled than malignant lesions (28% reactive) by this antibody; overall, 53 (41%) of 133 cases were positive for GCDFP-15. Notably, the tubuloglandular components in 17 (81%) of 21 pleomorphic adenomas were reactive, but no example of either adenoid cystic carcinoma or polymorphous low-grade adenocarcinoma were labeled. In contrast, 24% of adenocarcinomas stained with this antibody. The apparent expression of GCDFP-15 by a spectrum of salivary gland tumors supports their biologic relationship to lesions of the cutaneous apocrine glands and breast. Furthermore, the demonstration of this determinant may be of use in suggesting the salivary gland nature of poorly differentiated carcinomas of the head and neck, and it may facilitate the separation of pleomorphic adenoma from histologically similar malignant neoplasms in the salivary glands themselves.     

Bilateral apocrine carcinoma of the breast Molecular and immunocytochemical evidence for two independent primary tumours

Apocrine carcinoma is an uncommon variant of breast cancer. The frequency of bilaterality in patients who have apocrine carcinoma in one breast is not significantly different from that for bilateral mammary carcinomas in general, but bilateral apocrine carcinomas are very uncommon. We report on a bilateral apocrine carcinoma of the breast in a 74-year-old woman. The apocrine differentiation in both tumours was confirmed by the positivity of the cytoplasmic granules for PAS after diastase digestion and immunoreactivity for GCDFP-15 and sialyl-Tn. The tumour in the right breast showed immunohistochemical expression of p53, and a mutation was demonstrated by PCR-SSCP; the tumour in the left breast was negative for p53 on immunohistochemistry, and no mutation was found at the molecular level. c-erbB2 expression was not detected in the right tumour but there was overexpression (at the cell membrane) in the left tumour. Both tumours were aneuploid: the right tumour displayed multiple stemlines, whereas the left tumour had a triploid profile. Using the fluorescence in situ hybridization technique we demonstrated that both tumours displayed chromosome 17 polysomy and numerical abnormalities of chromosome 1, polysomy in the right and monosomy in the left tumour. We conclude that the two tumours are probably independent, as are most bilateral carcinomas of the breast.     

Mammaglobin vs GCDFP-15: an immunohistologic validation survey for sensitivity and specificity

There are limited data that compare the usefulness of mammaglobin with gross cystic disease fluid protein-15 (GCDFP-15) in the identification of breast carcinomas. Whole tissue sections of 29 breast carcinomas with matched lymph node metastases and 63 breast carcinomas on tissue microarray were stained with mammaglobin cocktail and GCDFP-15 antibodies. In addition, tissue microarrays (US Biomax, Rockville, MD) containing 544 different human tumors were also stained with the mammaglobin antibody cocktail. Positive staining was seen in 67 (55.4%) of 121 breast carcinomas with mammaglobin and in 28 cases (23.1%) with GCDFP-15. In the majority of cases, the staining intensity and number of cells staining were higher with mammaglobin than with GCDFP-15. Positive mammaglobin staining was also seen in 44 (8.1%) of 544 nonbreast tumors. Mammaglobin is a more sensitive marker than GCDFP-15 for breast carcinoma; however, it lacks the specificity of GCDFP-15.     

Value of gross cystic disease fluid protein-15 in distinguishing metastatic breast carcinomas among poorly differentiated neoplasms involving the ovary

Women with breast cancer have an increased risk of developing primary ovarian tumors. Because a differential diagnosis between primary and metastatic tumors may be difficult in poorly differentiated ovarian neoplasms, breast carcinoma markers may be helpful in establishing the primary site of origin. Gross cystic disease fluid protein-15 (GCDFP-15), a well-known marker of apocrine differentiation, has been reported as a highly specific and sensitive breast carcinoma marker. To evaluate the usefulness of GCDFP-15 as a marker for metastatic breast cancer, we have studied, by the avidin-biotin-peroxidase technique, 14 cases of breast cancer metastatic to the ovary and compared them with 32 primary ovarian tumors and seven cases of ovarian metastases other than breast in origin. Two cases of primary ovarian cancer metastatic to the breast were also included. A strong cytoplasmic immunostaining was found in 10 of 14 cases (71%) of ovarian metastasis from breast carcinoma, and in most cases a characteristic paranuclear staining was noted. All primary ovarian tumors were negative. Ovarian metastases from tumors other than breast and both cases of ovarian carcinoma metastatic to the breast were negative. These results are highly significant (P less than .00001) and demonstrate the value of GCDFP-15 in establishing a primary breast origin among neoplasms of unknown origin involving the ovaries.     

Histiocytoid breast carcinoma: Histological, immunohistochemical, ultrastructural, cytological and clinicopathological studies

Histiocytoid breast carcinoma (HBC) is a rare variant of breast carcinoma and often causes a diagnostic dilemma because of its histological similarities to some types of breast cancer and benign lesions. To elucidate the incidence of HBC and its biological properties, histological specimens from 1010 breast cancer patients treated at Yokohama Minami Kyosai Hospital between 1972 and 1996 were reviewed. Three cases of pure HBC and three cases of combined HBC (two with pleomorphlc lobular carcinoma and one with apocrine ductal carcinoma) were found, yielding an Incidence of 0.3% for each. Two of the three pure HBC cases contained foci of in situ lobular carcinoma. Targetoid and Indian file invasive patterns, the features characteristic of lobular carcinoma, were present in all three pure HBC cases and in two of the three combined HBC with pleomorphic lobular carcinoma. These results, together with those of previous studies, suggested that the majority of HBC are of lobular origin, although the apocrine ductai origin is also possible in a small number of HBC. Diastase-resistant periodic add-Schiff-positive granules and granular immunoreactivities for gross cystic disease fluid protein-15 (GCDFP-15) were characteristic of the histiocytoid tumor cells in both the pure and combined HBC, suggesting the apocrine differentiation of tumor cells. All three pure HBC cases were in stage 1 and were free of the disease for up to 5 years and 1 month after the lumpectomy. Thus, the prognosis of HBC appears to be dependent on the stage of the disease and may not always be poor, as indicated by the original report mentioning a preferential eyelid metastasis.