Sclerosing adenosis of the prostate gland. A clinicopathological and immunohistochemical study of 11 cases.

Eleven cases of sclerosing adenosis of the prostate gland, a recently reported uncommon pseudoneoplastic lesion with characteristic histological, histochemical, and immunohistochemical features, are described. The well-circumscribed cellular lesions were composed of variably sized and shaped, often compressed, glands and small clusters of epithelial cells embedded in a cellular, often myxoid stroma. Mild cytologic atypia was occasionally present, and one case had moderate cytologic atypia. A distinct basement membrane often surrounded the glands and clusters. Luminal acid mucin was typically present. Keratin-positive basal cells were present in the glands and as spindle cells in the stroma. The basal cells were also immunoreactive for S-100 and muscle-specific actin, suggesting myoepithelial differentiation. Clinical follow-up has shown no evidence of prostatic carcinoma. The available evidence suggests that sclerosing adenosis of the prostate gland is a benign lesion with distinctive features that should enable it to be distinguished from prostatic adenocarcinoma.     

Sclerosing adenosis of the prostate. Histopathologic and immunohistochemical analysis.

A prostatic lesion, histologically identical to sclerosing adenosis of the breast, was found in five (1.9%) of 263 patients who underwent transurethral resection, open prostatic adenectomy, radical prostatectomy, or total cystoprostatectomy. This uncommon lesion was a localized proliferation of crowded small glands, small solid nests, and individual cells embedded in a cellular stroma, mimicking a small acinar prostatic adenocarcinoma. The proliferating glands were lined by a single layer of secretory cells surrounded by an eosinophilic membranous structure. Basal cells were disclosed in individual glands or as small nests and even individual cells with immunostainability for basal cell-specific cytokeratin (EAB903), S-100 protein, and muscle-specific actin (HHF35). These findings indicate the benign nature of the lesion with myoepithelial differentiation of the basal cells. In contrast, all 25 small acinar adenocarcinomas examined as controls lacked positive stains for the above three antibodies, verifying the usefulness of these antibodies to distinguish between this benign lesion from adenocarcinoma.     

Sinonasal adenocarcinoma: immunohistochemical marking and expression of oncoproteins

BACKGROUND: Relatively little is known concerning the immunohistochemical marking of sinonasal adenocarcinoma (SNA). The most clinically problematic tumors are those that seem histologically identical to colonic adenocarcinoma, a neoplasm that may metastasize to the sinonasal region. To determine whether differentiated immunohistochemical expression of keratins could differentiate primary from metastatic tumors and to understand the biology of these tumors, differentiated keratin and oncoprotein expression was investigated. METHODS: Eleven patients with sinonasal adenocarcinoma were investigated for expression of cytokeratins 7 and 20 (CK7, CK20), AE 1/3, CAM 5.2, smooth muscle-specific actin, muscle-specific actin, desmin, S-100, carcinoembryonic antigen (CEA), p53, and HER-2/neu. RESULTS: All sinonasal adenocarcinomas of intestinal type were cytokeratin 7 positive. None of the tumors showed myoepithelial differentiation. Strong HER-2/neu staining was seen in some tumors. CONCLUSIONS: Strong HER-2/neu staining in some cases suggests this oncogene may be involved in the genesis of SNA. Immunohistochemical staining with cytokeratin 7 may be potentially useful in differentiating primary from metastatic disease in sinonasal adenocarcinomas of the intestinal subtype.     

Changes of phenotypic expression of prostatic antigen in secondary transitional cell carcinoma of the prostate: evidence for induction phenomenon as a mechanism for acquisition of prostatic antigens in prostatic transitional cell carcinoma

BACKGROUND: In vitro and experimental studies of mesenchymal-epithelial interaction for the prostatic stroma have demonstrated that the prostatic stroma is capable of inducing the nonprostatic epithelium to acquire many features of prostatic epithelium. We investigated whether this phenomenon could be observed in vivo in human prostatic stroma. MATERIALS AND METHODS Sixty transitional cell carcinoma (TCC) of the urinary bladder: (a) 20 with glandular lumen; (b) 20 without glandular lumen: (c) 10 mixed TCC-adenocarcinoma (ACA); and (d) 10 with synchronous or metachronous TCC of the prostate; and three primary TCC of the prostate were examined and submitted for immunostaining for prostatic acid phosphatase (PAP) and prostatic specific antigen (PSA). RESULTS: There was a spectrum of immunostaining for PSA ranging from negative reactivity in TCC without glandular lumen of the urinary bladder, to focal and weak reactivity in single cells with varying degrees of nonmucinous glandular differentiation and to strong reactivity in groups of cells in primary and synchronous or metachronous TCC in the prostate. The areas of carcinoma geographically closest to the prostate and with the most extensive nonmucinous glandular differentiation displayed the most frequent and strongest immunoreactivity for PSA. The immunoreactivity for PAP was usually stronger than for PSA. Four cases of TCC and mixed TCC-ACA were immunoreactive only for PAP. Furthermore, there was a change in the phenotype of TCC in the urinary bladder as it spread into the prostate. For 10 TCC in the urinary bladder with synchronous or metachronous tumor in the prostate, all TCC in the urinary bladder were negative for PAP and PSA, whereas six TCC in the prostate were focally positive. CONCLUSIONS: The spectrum of immunoreactivity for PAP and PSA and the change in immunoreactivity of TCC of the urinary bladder as it spreads into the prostate are likely induced by the prostatic stroma through the mechanism of mesenchymal-epithelial interaction. Prostate 47:172-182, 2001.     

A clinical and immunohistochemical study of papillary adenocarcinoma of the prostate

Clinical and immunohistochemical studies were conducted to evaluate prostatic papillary adenocarcinoma and prostatic papillary hyperplasia. Subjects consisted of 5 cases of papillary adenocarcinoma and 2 cases of papillary hyperplasia. There is no conclusive clinical factor for preoperative diagnosis, but we attach importance to endoscopic findings. PSA, PAP, high molecular weight cytokeratin, and PCNA were evaluated immunohistochemically. PSA became positive in every instance but one—a case of papillary adenocarcinoma which became ±. PAP was + in all cases, except for 1 case of papillary adenocarcinoma. Basal cells were positive for high molecular weight cytokeratin in 2 cases of papillary hyperplasia but were missing in papillary adenocarcinoma. Although PCNA was free from positive nuclei in papillary hyperplasia, positive nuclei were found in all cases of papillary adenocarcinoma. Considering these immunohistochemical results, papillary adenocarcinoma can be said to originate in the glandular epithelium of the prostate, as does ordinary prostatic carcinoma.     

Adenomyoepithelioma of the breast diagnosed by a mammotome biopsy: Report of a case

Adenomyoepithelioma is an uncommon primary breast tumor. It is conspicuous for two elements of the tumor, namely, ductal and myoepithelial components. Recently, a Mammotome biopsy, or stereotactic vacuum-assisted biopsy has become popular and various benign or borderline lesions are obtained. We report an adenomyoepithelioma of the breast in a 56-year-old woman. She was pointed out to have a cluster of some microcalcifications on mammography and a 9-mm hypoechoic mass lesion was detected by ultrasound. A Mammotome biopsy revealed a well-defined lesion. Histologically, the tumor demonstrated a thick and bi-cellular growth pattern consisting of ducts and myoepithelium. Immunohistochemically, epithelial cells were positive for cytokeratin AE1/AE3 and cytokeratin, epithelial membrane antigen (EMA), and carcinoembryonic antigen (CEA), negative for alpha-smooth muscle actin (alpha-SMA). In addition, myoepithelial cells were positive for alpha-SMA and CEA, which were scatterly positive for cytokeratin AE1/AE3, and negative for EMA. In examinations of non-palpable lesions found on mammography and ultrasound, a Mammotome biopsy is useful for making diagnosis, however, and adenomyoepithelioma is rarely found. In diagnosing such a rare disease from the limited information obtained from a needle biopsy, an immunohistochemical study was thus found to be useful for making a differential diagnosis.     

The distribution of S-100 protein in hyperplastic and neoplastic prostatic epithelium

Specimens from 30 cases of benign prostatichyperplasia and 75 cases of prostatic carcinomaobtained during suprapubic prostatectomy, transurethalresection of the prostate and radical prostatectomy,were stained immunohistochemically for S-100 protein,prostatic acid phosphatase (PAP), prostatic specificantigen (PSA), neuron specific enolase (NSE) andpolyclonal keratin. S-100 protein was positive in9.3% of prostatic carcinomas and negative in allcases of prostatic hyperplasia. PAP and PSA werepositive in all cases, while NSE was positive in 16%of the carcinoma cases. Polyclonal keratin waspositive in both cell layers of the double layeredhyperplastic prostatic epithelium with a more intensestaining pattern in the outer cell layer. The authorsbelieve that the S-100 protein immunoreactivityobserved in some prostatic carcinomas, reflecting thechange in the functional status of the neoplasticcells, might be of prognostic significance. They alsoemphasize the non-myoepithelial nature of the outercell layer of the double layered prostaticepithelium. This revised version was published online in August 2006 with corrections to the Cover Date.     

An immunohistochemical study of normal endometrial stroma and endometrial stromal neoplasms. Evidence for smooth muscle differentiation.

To determine the immunohistochemical staining profile of endometrial stromal cells, we analyzed a series of formalin-fixed, paraffin-embedded normal endometrial tissues, stromal nodules, and stromal sarcomas for immunoreactivity with a panel of eight antibodies. Normal proliferative-phase (five cases) and secretory-phase (five cases) endometrial stromal cells showed the following immunopositivity: vimentin 10 of 10, muscle-specific actin (MSA) 10 of 10, alpha-smooth muscle actin (alpha sm) 10 of 10, desmin nine of 10, cytokeratin (AE1/AE3 and CAM 5.2) zero of 10, epithelial membrane antigen (EMA) zero of 10, and S-100 protein zero of 10. Antibodies to vimentin, MSA, and alpha sm stained a greater number of proliferative-phase stromal cells as compared with secretory-phase cells. Only rare stromal cells were immunoreactive for desmin, except for one case in which predecidual cells were diffusely positive. Both endometrial stromal nodules reacted with antibodies to MSA, alpha sm, and desmin, and one was vimentin positive. Each was unreactive for epithelial markers and S-100 protein. The 12 endometrial stromal sarcomas had the following immunopositivity: vimentin 11 of 12, MSA 10 of 12, alpha sm 10 of 12, desmin seven of 12, AE1/AE3 one of 12, CAM 5.2 two of 12, EMA zero of 12, and S-100 protein zero of 12. The antibodies to MSA and alpha sm usually stained a greater number of cells than did the desmin antibody. Three stromal sarcomas had sex cord-like areas, one of which exhibited focal CAM 5.2 positivity. These immunohistochemical findings for normal and neoplastic endometrial stromal cells indicate smooth muscle differentiation and are similar to those of smooth muscle neoplasms and myofibroblastic cells.     

Immunocytochemical detection and phenotypic characterization of micrometastatic tumour cells in bone marrow of patients with prostate cancer

Monoclonal antibodies (mAbs) specific for cytokeratins are potent probes for the identification of disseminated individual epithelial tumour cells in mesenchymal organs such as bone marrow. We have used a monoclonal antibody (mAB) against cytokeratin 18 (CK18) for the detection of individual metastatic tumour cells in bone marrow aspirates from 84 patients with carcinoma of the prostate. CK18+cells were detected in a sensitivity of 1 per 8×10⁵ marrow cells using the alkaline phosphatase anti-alkaline phosphatase (APAAP) system for staining. We were able to detect CK18+tumour cells in the marrow of 33% of patients with stage N0M0 prostate cancers. The incidence of CK18+cells showed a significant correlation with established risk factors, such as local tumour extent, distant metastases and tumour differentiation. For further characterization of such cells in patients with prostate cancer, we developed an immunocytochemical procedure for simultaneous labelling of cytokeratin component no. 18 (CK18) and prostate-specific antigen (PSA). In a first step, cells were incubated with a murine mAb against PSA, followed by goldconjugated goat anti-mouse antibodies. In a second step, a biotinylated mAb to CK18 was applied as primary antibody and subsequently incubated with complexes of streptavidin-conjugated alkaline phosphatase, which were developed with Newfuchsin substrate. The binding of gold-labelled antibodies was visualized by silver enhancement. CK18+cells co-expressing PSA were found in bone marrow aspirates from 5 out of 14 patients with carcinomas of the prostate. The specificity of CK18 for epithelial tumour cells in bone marrow was supported by negative staining of 12 control aspirates from patients with benign prostatic hyperplasia (BPH). Thus the prostatic origin of CK+cells in bone marrow of patients with prostate cancer has been directly demonstrated for the first time in this work. In conclusion, the approaches presented appear to be reliable methods of identifying and phenotyping individual prostatic carcinoma cells and may help to identify those patients with prostate cancer who are at high risk of relapse.     

Prostatic carcinosarcoma: case report and review of literature

True carcinosarcoma of the prostate is a rare neoplasm, with only 9 cases well documented by immunocytochemistry and ultrastructural examination. We report a case of an unresectable pelvic tumor studied at autopsy. The primary prostatic neoplasm and pulmonary metastases were composed of well differentiated adenocarcinoma admixed with foci of leiomyosarcoma and osteosarcoma. The sarcomatous components showed reactivity with vimentin and desmin, did not express prostatic acid phosphatase (PAP) and prostate specific antigen (PSA), and contained myofilaments on electron microscopic examination. Positive staining of the carcinomatous component for PAP and PSA was noted. These findings confirm the mixed epithelial and mesenchymal components in primary and metastatic sites, and support the diagnosis of true prostatic carcinosarcoma.     

Middle Ear Adenomas Stain for Two Cell Populations and Lack Myoepithelial Cell Differentiation

Middle ear adenomas (MEAs) are benign neoplasms along a spectrum with neuroendocrine neoplasms (carcinoid tumors). Immunohistochemical (IHC) staining for myoepithelial markers has not been reported in these tumors. The archives of the Cleveland Clinic, University of Virginia and Armed Forces Institute of Pathology were retrospectively searched for tumors arising within the middle ear with material available for IHC staining. Twelve cases of MEAs, four cases of jugulotympanic paragangliomas (JPGs), 10 cases of ceruminous adenomas (CAs) and four cases of ceruminous adenocarcinomas (CACs) were obtained. IHC staining was performed for smooth muscle actin (SMA), p63, S-100 protein, cytokeratin 5/6 (CK5/6), and cytokeratin 7 (CK7). The MEAs were positive for: CK7 (92 %, luminal), CK5/6 (92 %, abluminal), p63 (83 %, abluminal), and negative for SMA and S-100 protein. The JPGs were negative for CK7, CK5/6, p63 and SMA; S-100 protein highlighted sustentacular cells. The CAs were positive for: CK7 (100 %, luminal), CK5/6 (100 %, abluminal), S-100 protein (80 %, abluminal), p63 (100 %, abluminal), and SMA (90 %, abluminal). CACs demonstrated two patterns, (1) adenoid cystic carcinoma-type: positive for CK7 (100 %, luminal), CK5/6, S-100 protein, p63, and SMA (all 100 %, abluminal); and (2) conventional-type: CK7 (50 % luminal), and no CK5/6, SMA, S-100 protein, or p63 expression. The IHC profile of MEAs suggests that these tumors harbor at least two cell populations, including luminal and basal cells. However, unlike ceruminous adenomas, MEAs lack true myoepithelial differentiation given the absence of S-100 protein and SMA staining in all cases.     

Reconstituted basement membrane promotes morphological and functional differentiation of primary human prostatic epithelial cells.

Prostatic epithelial cells undergo rapid proliferation and lose their ability to synthesize and secrete prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) under standard tissue culture conditions. Herein, we compared the morphology, growth, secretory activity, and intermediate filament expression of human prostatic epithelial cells cultured on either standard tissue culture plastic or reconstituted basement membrane. Epithelial cells grown on plastic exhibited a 10-fold increase in proliferation and a higher percentage of cells in the S-phase of the cell cycle compared to cells cultured on basement membrane. However, cells grown on basement membrane secreted markedly higher levels of PSA and PAP. The basement membrane-induced enhancement of secretory activity was potentiated by dihydrotestosterone (DHT) and prostate stromal cell conditioned medium. Morphological studies showed that cells plated on basement membrane formed organoid-like clusters and maintained several aspects of differentiated epithelium including abundant secretory vesicles, microvilli, and desmosomes with associated cytoskeletal elements. Cultivation of epithelial cells on basement membrane components also suppressed the expression of vimentin, a mesenchymal intermediate filament polypeptide. However, cytokeratin expression was abnormal in cells grown on either surface. These results indicate that the differentiated properties of prostatic epithelial cells are promoted by cultivation on reconstituted basement membrane in the presence of DHT and stromal cell conditioned medium.     

Histogenesis of benign pleomorphic adenoma (mixed tumor) of the major salivary glands. An ultrastructural and immunohistochemical study

Twenty-two benign pleomorphic adenomas of the major salivary glands were studied by transmission electron microscopy and immunohistochemical techniques (three cases) in order to characterize the cell types comprising the epithelial and so-called mesenchymal regions of the tumors. Light- and electron-microscopic studies showed the tumors to consist of variable mixtures of neoplastic ductular epithelial cells, rare acinar cells, and metaplastic myoepithelial cells. Many of the loosely organized "stromal cells" contained structures indicative of their myoepithelial origin, e.g., perinuclear tonofilaments, ectoplasmic actin microfilaments, and remnants of basement membrane. Polyclonal antikeratin antisera strongly stained ductular epithelial and myoepithelial cells, squamoid cell nests, and periductular myoepithelial cells, whereas myxoid and chondroid cells were less intensely stained. Monoclonal cytokeratin antibody AE1 stained only the ductular epithelial cells in both the normal glands and tumors. In contrast, S-100 protein, which is present only in scattered acinar cells and myoepithelial cells in the normal parotid gland, was found in the ductular and periductular myoepithelial cells, isolated myxoid cells, and chondroid and cartilagenous cells in the tumors. Actin was found in all the cell types of the tumor but staining was strongest in the ducts. Double immunofluorescence staining for cytokeratin and vimentin revealed coexpression of both types of intermediate filaments in occasional normal acinar and intercalated duct myoepithelial cells, and in some cells in the myxoid and chondroid regions of the tumors. In the tumors, vimentin was present in occasional periductular myoepithelial cells, stellate myxoid cells, and especially in chondroid cells and chondrocytes. Our findings indicate that benign pleomorphic adenomas of the major salivary glands are pure epithelial cell tumors. The histologic complexity of these neoplasms is due to the ability of the neoplastic ductular myoepithelial cell to modulate its morphologic appearance and intermediate filament composition, and to produce large amounts of matrix substances. We further postulate that these tumors arise from neoplastically transformed intercalated ducts.     

Invasive Breast Carcinoma Arising in Microglandular Adenosis: A Case Report and Review of the Literature

Abstract:  Microglandular adenosis of the breast is an extremely rare, benign lesion. Carcinoma arising in microglandular adenosis has been reported in up to 27% of patients with microglandular adenosis. We reported a case of invasive carcinoma arising in microglandular adenosis. A lumpectomy was performed on a 42-year-old female because of a mass in the right breast. Grossly, the lesion was ill-defined with thickened areas. Histologically, this case was consistent with carcinoma arising in microglandular adenosis and showed clear transition from microglandular adenosis through atypical microglandular adenosis to in situ and invasive carcinoma. All the epithelial cells were positive for cytokeratin7, S-100 protein, but negative for estrogen receptor, progesterone receptor, and Her2/Neu. No myoepithelial cells were demonstrable with immunohistochemical staining for smooth muscle actin, muscle-specific antigen or P63. Periodic acid-Schiff staining showed the presence of a basement membrane in microglandular adenosis, atypical microglandular adenosis, in situ carcinoma and the absence in invasive carcinoma. To the best of our knowledge, this is the first reported case of carcinoma arising in microglandular adenosis in China.     

Human glandular kallikrein 2 (hK2) expression in prostatic intraepithelial neoplasia and adenocarcinoma: A novel prostate cancer marker

Objectives. We describe the expression of a potentially new tumor marker, human glandular kallikrein 2 (hK2), that may be useful as an adjunct to prostate-specific antigen (PSA) in the diagnosis and monitoring of prostate cancer.Methods. We evaluated 257 radical prostatectomy specimens removed at the Mayo Clinic with pathologic Stage T2 adenocarcinoma to compare the cytoplasmic expression of hK2, PSA, and prostatic acid phosphatase (PAP) in benign tissue, high-grade prostatic intraepithelial neoplasia (PIN), and adenocarcinoma. Two monoclonal antibodies, hK2-A523 and hK2-G586, specific for hK2 were used, as well as antibodies against PSA (PSM-773) and PAP (polyclonal).Results. Intense epithelial cytoplasmic immunoreactivity was observed in every case for hK2-A523, hK2-G586, PSA, and PAP (100% of cases, respectively). The intensity and extent of hK2 expression for both antibodies were greater in cancer than high-grade PIN; furthermore, high-grade PIN was greater than benign epithelium. Cases of Gleason primary grade 4 and 5 cancer showed hK2 staining in almost every cell, whereas there was greater heterogeneity of staining in lower grades of cancer. In marked contrast to hK2, PSA and PAP immunoreactivity was most intense in benign epithelium and stained to a lesser extent in PIN and carcinoma. The number of immunoreactive cells for hK2 and PSA was not predictive of cancer recurrence.Conclusions. hK2 was expressed in every cancer, and the expression incrementally increased from benign epithelium to high-grade PIN and adenocarcinoma. PSA and PAP displayed inverse immunoreactivity compared with hK2. The expression of hK2 and PSA was not predictive of cancer recurrence in patients with Stage T2 carcinoma. Expression of hK2 indicates that this kallikrein antigen is both prostate localized and tumor associated. Tissue expression of hK2 appears to be regulated independently of PSA and PAP. Further studies are needed to determine whether tissue immunoreactivity of hK2 will prove clinically useful in the diagnosis and monitoring of prostate cancer.     

Immunohistochemical characterization of neuroendocrine cells in prostate cancer

BACKGROUND: Neuroendocrine (NE) cells increase in high grade/stage prostate cancer (PC) and may contribute to androgen-independent cancer. Their immunohistochemical phenotype has not been studied in detail and conflicting results have been reported. METHODS: PC tissue was stained immunohistochemically for luminal secretory cell-associated cytokeratin, basal cell markers, ki-67, androgen receptor (AR), PSA, prostate acid phosphatase (PAP), and alpha-methylacyl coenzyme A racemase (AMACR). RESULTS: The NE cells are positive for AE1/AE3, Cam 5.2, and negative for basal cell markers. They are negative for AR, PSA, and Ki-67 but positive for PAP. The benign NE cells are negative for AMACR while the malignant NE cells are positive for AMACR. CONCLUSIONS: NE cells of PC constitute a unique subset of cancer cells, which have a unique immunohistochemical profile. They do not express AR, consistent with their resistance to hormonal therapy. They are post-mitotic cells but are malignant and part of the tumor.     

Esophageal gland duct adenoma: immunohistochemical comparison with the normal esophageal gland and ultrastractural analysis

Esophageal gland duct adenomas are extremely rare tumors. Here, we report the case of a 75-year-old Japanese man who had undergone total gastrectomy for advanced gastric cancer. Esophageal gland duct adenoma was incidentally found in the lower esophagus. It appeared to be detached from the site of gastric cancer and was well demarcated without a capsule. Histologic analysis revealed papillary and cystic structures mainly comprising eosinophilic cells with minimum nuclear atypia. Immunohistochemical analysis revealed that the tumor were diffusely positive for the S100 protein with preserved alpha-SMA-positive myoepithelial cell layers and a characteristic cytokeratin expression pattern similar to that in normal esophageal gland ducts (CK5/6+++, CK7+++, CK17+, CK18+, CK19+++, CK20-, HMWCK+++). In addition, differentiation into the terminal duct was confirmed by a combination of mucin staining and immunohistochemical and ultrastructural examinations. This is the first report that refers to the ultrastructural findings of an esophageal gland duct adenoma and describes terminal duct differentiation. We believe that the possibility of an esophageal gland duct adenoma should be considered when diagnosing a ductal or glandular lesion of the esophagus.     

Monophasic fibrous and poorly differentiated synovial sarcoma: immunohistochemical reassessment of 60 t(X;18)(SYT-SSX)-positive cases

Diagnosing monophasic fibrous and poorly differentiated synovial sarcoma (SS) on morphology alone is often a source of problems for pathologists. SS bear the t(X;18)(p11.2,q11.2) translocation, which proved to be specific for this tumor type and is currently considered one of the most reliable diagnostic criteria. To evaluate the sensitivity of immunohistochemical techniques in diagnosing monophasic fibrous SS (MFSS) and poorly differentiated SS (PDSS), we examined 60 t(X;18)(SYT-SSX)-positive cases (47 MFSS and 13 PDSS) for cytokeratin AE1/AE3, cytokeratin KL1, epithelial membrane antigen, E-cadherin, CD34, S-100 protein, alpha-smooth muscle actin, desmin, h-caldesmon, CD99, bcl2, and C-kit (CD117) antibodies. Of the four epithelial markers tested, epithelial membrane antigen proved to be the most sensitive, reacting with 100% of MFSS and 92% of PDSS, followed by cytokeratin AE1/AE3 (70% of MFSS, 46% of PDSS), cytokeratin KL1 (49% of MFSS, 38% of PDSS), and E-cadherin (47% of MFSS, 54% of PDSS). A staining for cytokeratin AE1/AE3 and/or E-cadherin was observed in 79% of MFSS and 69% of PDSS, and a staining for cytokeratin KL1 and/or E-cadherin was observed in 74% of MFSS and 62% of PDSS. S-100 protein was positive in 38% of MFSS and 23% of PDSS, and alpha-smooth muscle actin in 21% of MFSS and 8% of PDSS. Tumor cells were rarely positive for CD34 (6% of MFSS, 0% of PDSS) and desmin (2% of MFSS, 0% of PDSS). Most SS were strongly positive for bcl-2 (91% of MFSS, 92% of PDSS) and CD99 (91% of MFSS, 100% of PDSS). A weak and focal cytoplasmic reactivity for CD117 was observed in 11% of MFSS (only one case had a strong immunoreactivity) and 8% of PDSS. Staining with h-caldesmon was consistently negative. In conclusion, in keeping with literature data, our results show that reactivity for epithelial membrane antigen, cytokeratin AE1/AE3, and E-cadherin, in combination with CD34 negativity, are the most useful and sensitive markers for diagnosing monophasic fibrous and poorly differentiated t(X;18)-positive SS. They also support the fact that about one third of MFSS and one fourth of PDSS are positive for S-100 protein, a finding of diagnostic relevance when considering their distinction from other spindle to round cell sarcomas, especially malignant peripheral nerve sheath tumors.     

Myoepithelial carcinoma of the salivary glands: a clinicopathologic study of 25 patients

Salivary gland carcinomas displaying exclusively myoepithelial differentiation (myoepithelial carcinoma) are considered rare. Their histopathologic features, immunohistochemical profile, and clinical behavior are not well characterized. The authors reviewed the clinicopathologic features of 25 salivary gland tumors fulfilling two fundamental histologic criteria: unequivocally malignant and exclusively myoepithelial. For most of these, the original diagnosis was malignant mixed tumor. Thirteen men and 12 women aged 24 to 77 years (mean age, 55 yrs) participated in the study, and most presented with a painless mass. The parotid gland was the most common site (n = 15). Tumors ranged from 2.1 to 5.5 cm, arising either in association with a benign mixed tumor (n = 15) or de novo (n = 10). Histologically, all the tumors displayed infiltrative growth and most had a characteristic multinodular architecture with a cellular periphery and central necrotic/myxoid zones. Epithelioid, hyaline, spindle, clear, or mixed cell types were noted with accompanying myxoid and/or hyalinized extracellular matrix. Ten tumors were high grade cytologically and 15 were low grade. The mitotic rate ranged from three to 51 mitoses per 10 high-power fields. Necrosis was present in 15 tumors and perineural and vascular invasion were identified in 11 and four neoplasms respectively. Immunoreactivities included CAM5.2 (89%), AE1:AE3 (100%), 34betaE12 (92%), cytokeratin 7 (21%), cytokeratin 14 (53%), vimentin (100%), S-100 protein (100%), smooth muscle actin (50%), calponin (75%), muscle-specific actin (31%), glial fibrillary acidic protein (31%), carcinoembryonic antigen (0%), and epithelial membrane antigen (21%). Ultrastructural examination of three tumors showed myoepithelial features. Ten patients developed recurrences, mostly multiple. Follow up of 17 patients showed that eight patients (47%) developed metastases (six high grade, two low grade) and five patients (29%) died of disease (four high grade, one low grade) after a mean of 32 months. Two patients were alive with disease (19 and 49 mos). Ten patients (59%) were without any evidence of disease after a mean of 42.2 months. Myoepithelial carcinomas exhibit a wide spectrum of cytomorphologic features and diverse clinical outcomes. As a result of their morphologic heterogeneity, they can be confused easily with many tumors. Myoepithelial carcinomas have been underrecognized in the past, primarily by being lumped under a broader category of "malignant mixed tumor." Awareness of their unique cytoarchitectural patterns and immunohistochemical profile is crucial for accurate identification.