Beta E12 Research Articles

Sarcomatoid (Spindle Cell) Carcinoma Arising in Mature Cystic Teratoma as a Mural Nodule: A Case Report

Mature cystic teratomas are the most common ovarian germ cell tumours.Malignant transformation is rare in mature cystic teratoma. Spindle cell/sarcomatoid carcinoma is an uncommon type of squamous cell carcinoma. A 45-year- old female presented with abdominal distention and discomfort. Magnetic Resonance Imaging (MRI) showed multiloculated cystic mass measuring 21×20×14 cm with heterogeneously enhancing solid component measuring 5x3.5 cm in right adnexal region. Excision of the mass done. Macroscopic examination showed irregular cystic mass containing pultaceous material and hair, and a mural nodule measuring 5x5 cm. On histopathological examination, the cyst wall showed mature teratomatous elements. Sections from mural nodule showed sheets of atypical spindle cells with increased mitosis and foci of necrosis. On immunohistochemical examination, the spindle cells showed patchy weak to moderate positivity for cytokeratin, 34 beta E12, CK5/6 and P40. Diagnosis of spindle cell/sarcomatoid carcinoma arising in mature cystic teratoma was given. Malignant transformation in mature cystic teratoma is rare and should be suspected in large sized tumours in older patients. Sarcomatoid carcinoma is an extremely rare form of secondary malignant neoplasm arising from mature cystic teratoma.

Diagnostic Value of Cytokeratin 34 beta E12 (Ck34βE12) and α-Methylacyl-CoA racemase (AMACR) Immunohistochemical Expression in Prostatic Lesions.

Background & Objective:Some prostatic lesions contain small suspicious foci for prostatic carcinoma in which the morphological features are equivocal. Two immunohistochemical markers namely, cytokeratin 34 beta E12 (Ck34βE12) and α-Methylacyl-CoA racemase (AMACR), were evaluated in these lesions for a definitive diagnosis and avoiding misdiagnosis or overdiagnosis of prostatic carcinoma.Methods:A total of 90 paraffin embedded blocks of prostatic tissue were selected and categorized into three groups as follows: 50 cases of benign prostatic hyperplasia (BPH), 20 cases of prostatic carcinoma, and 20 cases of benign prostatic lesions with suspicious foci labeled as ASAP (atypical small acinar proliferation) that occupy not more than 5% of the lesion. These cases were revised for histopathological diagnosis and stained with two immunohistochemical markers: Ck34βE12 and AMACR.Results:While 92.9% of BPH were positive for Ck34βE12, 96% of prostatic carcinoma were negative for this marker (P=0.0001). Regarding AMACR, 92.9% of BPH cases were negative, but 92% of prostatic carcinoma cases were positive for this marker (P=0.0001). Out of 20 cases of BPH, 15 cases containing suspicious foci showed Ck34βE12+/AMACR- (diagnosis: benign), but 5 cases were Ck34βE12-/AMACR+, for which the diagnosis changed to prostatic carcinoma (P=0.04).Conclusion:Immunohistochemical staining with Ck34βE12 and AMACR improved the diagnostic performance and increased confidence level for establishing definite diagnosis in cases with suspicious foci, in which the morphological features were equivocal. This could help to avoid misdiagnosis or overdiagnosis of prostatic carcinoma that would eventually improve the management of the patient and subsequently the prognosis.

Morphologic, Immunohistochemical and Molecular Analyses of a Huge Clear Cell Papillary Renal Cell Carcinoma

Among the tumors of the kidney, the clear cell papillary renal cell carcinoma (CCPRCC) is a recently described entity. This tumor is well circumscribed, with a fibrous capsule, showing mostly a prominent cystic component and a diameter less than 4 cm. Necrosis is not a feature. Tumor cells are clear with low grade nuclei with a predominantly tubule-papillary architecture and immunohistochemical staining strongly positive for CK7, and for CA IX and negative for RACEMASE, features which differentiate this tumor from clear cell renal cell carcinoma (CCRCC) and papillary renal cell carcinoma (papillary RCC). In these latter tumors, it has been reported, unlike the other two, no loss or gain of chromosomes 7 and Y, no chromosome 3p deletion, and no KRAS mutation. In this report, a huge clear cell papillary renal cell carcinoma case, 9 cm diameter, in a 42-year-old male is described. Pathologic diagnosis of the tumor was confirmed by immunohistochemical analysis including CD10, CA IX, CK7, RACEMASE, and 34 beta E12 stainings. Molecular detection of KRAS, BRAF, NRAS, PIK3CA, ALK, ERBB2, DDR2, MAP2K1, RET, and EGFR gene mutational analysis has also been performed. Molecular findings are in accordance with the speculation that the CCRCC is an indolent tumor which may be defined as low malignant potential. In fact, in the molecular analysis, none out of all genes evaluated showed mutation.

MP21-13 FUNCTIONAL ROLES OF METABOTROPIC GLUTAMATE RECEPTOR SUBTYPE 1A IN CONTROL OF LOWER URINARY TRACT ACTIVITY IN MICE

distribution in an intact prostate. 34bE12 staining of clarified seminal vesicle prominently labeled all the basal cells. To explore the feasibility of multi-rounds of molecule phenotyping, anti-S100 was stripped from the bladder and anti-UPIa and 34beta E12 were used for re-staining. Anti-UPIa specifically labeled the superficial umbrella cells, whereas 34bE12 stained the basal cells of the urothelium. CLARITY preserved the fine structure of all GU samples tested and multiple rounds of molecular phenotyping did not cause any tissue damage. CONCLUSIONS: This is the first report of the use of CLARITY in mouse GU tissues. Our preliminary work shows that CLARITY has the ability to analyze GU organs, repetitively with multiple antibodies which can be compared to molecular data to further our understanding of normal and pathological states.

Immature ovarian teratoma with unusual gliomatosis

This study aimed to investigate an unusual case of immature ovarian teratoma with onset of mature glial cells implanted on the contralateral ovary, a challenge in the diagnosis of the second ovarian tumor. We report the case of a 31- yr-old woman, who developed at the age of 16 an immature teratoma in the right ovary that was surgically removed. Six years later mature glial implants were present on the left ovary and six months later at the level of peritoneum that relapsed after other six months. The patient suffered three surgical resections after the initial one. Paraffin sections and immunohistochemical examinations using antibodies against glial and neuronal antigens were performed. In the teratoma, the neuroectodermal tissue expressed Glial fibrillary acidic protein (GFAP), S100 protein, Epithelial membrane antigen (EMA) and Cytokeratin 34 beta E12 (Ck34beta E12), wheares the implants expressed only GFAP and S100 protein. The immature teratoma is the rarest type of ovarian teratomas. Gliomatosis peritonei is an exceptional finding, expecially with onset on the contralaterally ovary. The implant of the mature glial cells has a high risk of relapse, as seen in our case, thus close follow-up of the patient is necessary.

Metaplastic Breast Carcinoma: A Case Report

INTRODUCTION: Metaplastic breast carcinoma is a rare condition, representing less than 1% of the invasive carcinomas of the breast. These tumors, in addition to the carcinomatous component, are constituted by mesenchymal, fusocellular and squamous dominant elements. They are characterized by a high growth rate, aggression and immunohistochemical characteristics of the basal-like carcinomas of the breast (triple negative). REPORT: An eighty six years old lady, first seen at September 2011, at the Breast Surgery Department at Hospital das Clinicas, Universidade Federal de Minas Gerais, Brazil. She had a complaint of a palpable mass at her right breast. On her physical exam there was palpable mass of 5 cm at her right breast, extending to the axilla, consistent of a clinical staging of T4bN0M0. Her mammogram showed a spiculated nodule in axillary tail of Spence at the right breast, BIRADSTM 5. Her breast ultrasound showed a spiculated hypoechoic nodule of 3. 6 cm at the outer quadrant of her right breast, BIRADSTM 5. Incisional biopsy was performed, positive for a spindle cell neoplasm with a low mitotic index - this could represent a mesenchymal (fibrosarcoma) or mammary neoplasm (myofibroblastoma or spindle cell metaplastic carcinoma). Immunohistochemistry was positive for a metaplastic spindle cell carcinoma. Family at first did not allow the surgical procedure, which delayed her treatment. When authorized by the family, surgery was performed in March 2012 and she underwent a radical modified mastectomy. Her pathological findings were: metaplastic breast carcinoma type fibrosarcoma with mild cell pleomorphism, low histological grade, skin infiltrated by contiguity and free surgical margins. pT3(5, 5)N0(0/10)M0. New immunohistochemistry was performed at the surgical specimen compatible with a metaplastic spindle cell carcinoma (staining strongly positive for AE1/AE3, 34 beta E12 and p60). In July 2012, the patient was asymptomatic with no signs of local or systemic recurrence. She is regularly followed by the breast surgeons and clinical oncologists. DISCUSSION: Metaplastic breast carcinoma is associated with a faster local growth and a worse prognosis compared to ductal carcinomas. These metaplastic tumors show, in general, negative hormone receptors and Her2 negative on immunohistochemistry. In contrast, immunohistochemistry is often crucial in differentiating metaplastic carcinoma and primary sarcomas of the breast. The correct diagnosis of metaplastic carcinoma, differential diagnosis of sarcomas and invasive ductal carcinoma is important for proper treatment and prognosis. In relation to the metastatic potential, metaplastic tumors have higher rates of hematogenous metastases and lower rates of lymph node metastasis. There are no conclusive studies about the benefit of adjuvant chemo and radiation therapy, which makes surgery the main treatment.

Characterization of lacrimal sac histology: an immunohistochemical study

A prospective observational study in a university hospital setting to study the immunohistochemical (IHC) characteristics of non-neoplastic human lacrimal sac epithelium. Twenty paraffin-embedded specimens of human lacrimal sac were studied using monospecific monoclonal antibodies to 34 beta E12, cell adhesion molecule (CAM 5.2), epithelial membrane antigen (EMA), cytokeratins (CK) 7 and 20, estrogen receptor and progesterone receptor. The distribution and histologic location of IHC staining were examined qualitatively, and the IHC stains scored as positive (+) or negative (-). The haematoxylin-eosin stains were reviewed for tissue morphology. All 20 specimens were positive for 34 beta E12, CAM 5.2, EMA and CK 7 and negative for CK 20, estrogen receptor and progesterone receptor. To our knowledge, this is the first study to characterize the IHC properties of human lacrimal sac epithelium. This epithelium appears to possess consistent IHC properties as it stains for 34 beta E12, CAM 5.2, EMA and CK 7 and this information would be potentially useful in differentiating tumours arising in the region of the lacrimal sac.

Diagnostic utility of α-methylacyl CoA racemase (P504S) & HMWCK in morphologically difficult prostate cancer

BackgroundTo evaluate the diagnostic utility of alpha-methylacyl CoA racemase (P504S) & HMWCK (34beta E12) in morphologically difficult prostate cancer.MethodsA total of 1034 cases were reviewed and divided into benign (585) malignant (399) and suspicious (50). Immunohistochemistry with HMWCK and AMACR was done on the 50 suspicious cases along with controls.ResultsForty nine suspicious cases were resolved by using both markers where as 1 case was resolved by further support with CD68. The original diagnosis was changed in 15 of 50 (30%) suspicious cases from benign to malignant, one case from benign to high grade PIN and in one case from malignant to benign. Change of diagnosis was seen in 17 of 50 (34%) suspicious cases with a significant p value of 0.002. The overall diagnosis was changed in 17 of 1034 cases (1.64%) of prostatic disease (p < 0.001).ConclusionsA combination of HMWCK and AMACR is of great value in combating the morphologically suspicious cases and significantly increasing the diagnostic accuracy in prostate cancer. Although, in this study the sensitivity and specificity of HMWCK and AMACR were high, yet it should be used with caution, keeping in mind all their pitfalls and limitations.

Pleomorphic carcinoma of the breast in a 17-year-old woman

We report a 17-year-old woman with refractory high-grade breast cancer who died early after surgery, with reference to the histogenesis of the cancer. Macroscopically, the tumor was cystic, composed of a mixture of solid and myxomatous areas. Histologically, the tumor exhibited ductal structures and areas with squamoid features. Cancer cells were markedly atypical and polymorphic, and included a mixture of bizarre and eosinophilic cells with rhabdoid feature-like free cells. Immunohistochemically, cytokeratin (CK) 8, CK 18, 34 beta E12, CD10, involucrin, CK14, and vimentin were partially positive, whereas estrogen and progesterone receptors and HER-2 were negative. These findings suggest an undifferentiated cancer whose cells have multilineage potential to differentiate into mesenchymal, basal, and squamoid cells, and it was diagnosed as pleomorphic carcinoma, which is a histological type hitherto unreported in young girls. The cancer was refractory to treatment, and the patient died 1 year and 5 months after surgery despite chemotherapy and radiotherapy.

Immunohistochemical Distinction of Cutaneous Spindle Cell Carcinoma

Cutaneous spindle cell squamous carcinoma is an uncommon variant of squamous cell carcinoma in which keratinocytes infiltrate the dermis as single cells with elongated nuclei rather than as cohesive nests or islands, and signs of keratinization of conventional squamous cell carcinoma are insubstantial or nonexistent. Spindle cell carcinoma must be distinguished from spindle cell/desmoplastic melanoma, cutaneous leiomyosarcoma, atypical fibroxanthoma (AFX), and scar. In instances when there is no definitive evidence of squamous differentiation, immunohistochemical studies may confer diagnostic discrimination. Twenty-four cases consisting of 12 spindle cell squamous cell carcinomas, 3 AFXs, 3 leiomyosarcomas, 3 desmoplastic melanomas, and 3 scars were evaluated with a battery of immunohistochemical stains, with the specificity and sensitivity of each marker calculated. The immunohistochemical battery consisted of S-100, desmin, CD68, and smooth muscle actin and cytokeratins P KER (keratins predominantly of molecular weight 56 and 69 kd) and low-molecular weight keratin (CAM 5.2), AE1/AE3, p63, and 34 beta E12 (CK903). Spindle cell squamous carcinomas were negative for S-100, CD68, smooth muscle actin, and desmin with the exception of 2 cases with weak staining for smooth muscle actin. 34 beta E12 provided positive results for each spindle cell squamous carcinoma. The other cytokeratin stains were less sensitive for spindle cell squamous carcinoma than 34 beta E12. The final immunohistochemical results were as follows: 34 beta E12 (12/12, 100%), p63 (10/12, 80%), AE1/AE3 (8/12, 67%), low-molecular weight keratin (7/12, 58%), and P KER (4/12, 33%). The 3 AFXs were positive for CD68 and negative for all other stains, whereas the 3 leiomyosarcomas stained positively for desmin and smooth muscle actin and negatively for all other stains. The 3 melanomas stained positively for S-100 and negatively for all other immunohistochemistry. The scars were negative for all stains. In conclusion, our study of 34 beta E12 proved most promising in distinguishing spindle cell squamous carcinoma from the histologic mimickers, AFX, spindle cell melanoma, scar, and leiomyosarcoma.

Human Nasal Turbinates as a Viable Source of Respiratory Epithelial Cells Using Co‐Culture System Versus Dispase Dissociation Technique

To compare a co-culture system with a conventional dispase-dissociation method for obtaining functional human respiratory epithelial cells from the nasal turbinates for tissue engineering application. Human respiratory epithelial cells were serially passaged using a co-culture system and a conventional dispase-dissociation technique. The growth kinetics and gene expression levels of the cultured respiratory epithelial cells were compared. Four genes were investigated, namely cytokeratin-18, a marker for ciliated and secretory epithelial cells; cytokeratin-14, a marker for basal epithelial cells; MKI67, a proliferation marker; and MUC5B, a marker for mucin secretion. Immunocytochemical analysis was performed using monoclonal antibodies against the high molecular-weight cytokeratin 34 beta E12, cytokeratin 18, and MUC5A to investigate the protein expression from cultured respiratory epithelial cells. Respiratory epithelial cells cultured using both methods maintained polygonal morphology throughout the passages. At passage 1, co-cultured respiratory epithelial showed a 2.6-times higher growth rate compared to conventional dispase dissociation technique, and 7.8 times higher at passage 2. Better basal gene expression was observed by co-cultured respiratory epithelial cells compared to dispase dissociated cells. Immunocytochemical analyses were positive for the respiratory epithelial cells cultured using both techniques. Co-culture system produced superior quality of cultured human respiratory epithelial cells from the nasal turbinates as compared to dispase dissociation technique.

Pleomorphic lobular carcinoma in situ of the breast composed almost entirely of signet ring cells

Some examples of lobular carcinoma in situ (LCIS) may be composed in part of signet ring cells. Such proliferations have been considered examples of pleomorphic LCIS based on pathological features of the more conventional component. However, the occurrence of LCIS composed entirely of signet ring cells is extraordinarily rare. This report describes an example of an in situ proliferation that was composed almost entirely (>95%) of signet ring cells, which was unassociated with an invasive carcinoma and which showed comedo-type necrosis. There was only focal lobulocentric distention by lesional cells, as is typical of classic LCIS. However, discrete, ductal-type cross-sectional profiles showed a purely intraepithelial proliferation of remarkably discohesive signet ring cells. The signet ring cells had intermediate-grade nuclear atypia, no significant mitotic activity and were positive for mucicarmine and PAS stains (the latter with and without diastase predigestion). The cells displayed marked immunoreactivity for high-molecular-weight keratin (stained by 34beta E12 antibody), MUC1, gross cystic disease fluid protein-15, cytokeratin 7 and were negative for cytokeratin 20, E-cadherin, progesterone receptor and HER2/neu. It is concluded that this is an example of a purely signet ring variant of pleomorphic LCIS.

Intrahepatic cholangiocarcinoma arising in cirrhotic liver frequently expressed p63-positive basal/stem-cell phenotype

In general, intrahepatic cholangiocarcinoma (ICC) is not related to liver cirrhosis. However, a few cases have been reported in which ICC was accompanied by severe liver fibrosis. Some researchers have proposed that hepatocellular and cholangiocellular (HC–CC) carcinoma, an intermediate mixed phenotype possibly arising in cirrhotic liver, might originate from hepatic precursor cells. In the liver, hepatocytes and cholangiocytes form the epithelial element, but stromal and mesenchymal elements may be produced by hepatic stem cells. Based on these aspects, not only HC–CC, but also other combinations of cellular phenotypes, would cover all the cancers with stem cell features. In this study, which aimed at determining the characteristics of the ICC phenotype, we used immunohistochemistry to examine the expression of basal/stem-cell markers, i.e., p63 in ICC with and without liver cirrhosis, as well as the expressions of cytokeratin (CK) 34 beta E12, specific for the basal-cell marker, and c-kit, specific for the stem-cell marker. Aberrant p63 was frequently expressed in ICC arising in cirrhotic liver. This result suggests that ICC cancer cells originate from hepatic precursor cells with a hidden multi-differentiation potential.

Large cell neuroendocrine carcinoma of the lung: a comparison with large cell carcinoma with neuroendocrine morphology and small cell carcinoma

Large cell neuroendocrine carcinoma (LCNEC) of the lung is a malignant neuroendocrine tumor clinicopathologically similar to and falling in-between atypical carcinoid tumor and small cell lung carcinoma (SCLC). The diagnosis of LCNEC is based mainly on a characteristic neuroendocrine morphology and biological neuroendocrine differentiation. In order to know the discrepancy between morphological and biological neuroendocrine differentiation, LCNEC was immunohistochemically and molecular biologically compared with large cell carcinoma with neuroendocrine morphology (LCCNM), which lacked only biological neuroendocrine differentiation among the criteria of LCNEC. Immunohistochemically, disruption of the RB pathway, namely a lack of RB expression and simultaneous overexpression of p16 protein, was characteristic of LCNEC, but not LCCNM. In G2/M cell cycle regulation, 14-3-3 sigma expression was markedly reduced in LCNEC. Moreover, the antibody 34 beta E12 recognizing a set of large-sized keratin gave a different staining pattern between LCNEC and LCCNM. The immunohistochemical data suggested that LCNEC has a similar biological marker profile to SCLC and different from LCCNM. However, a loss of heterozygosity (LOH) analysis using microsatellite markers showed a high frequency of LOH at 3p in both LCNEC and LCCNM as well as in SCLC. Morphological neuroendocrine differentiation might not be identical to biological neuroendocrine differentiation in large cell carcinoma of the lung.

Prostate carcinoma with squamous differentiation: an analysis of 33 cases.

Only sporadic cases of prostate carcinomas with squamous differentiation have been reported. The files of two institutions were reviewed for prostate cancers with squamous differentiation. A total of 33 cases were studied. The average age at diagnosis was 68 years (range 49-86 years). The most common presenting symptoms included bladder outlet obstruction and dysuria. Thirteen men had a positive digital rectal examination. Diagnosis was made by needle biopsy (n = 23); transurethral resection of the prostate (n = 5); needle and transurethral resection of the prostate (n = 1); transurethral resection of the bladder (n = 1); or biopsy of metastases (n = 3). In 21 of 33 cases, there was a prior diagnosis of adenocarcinoma of the prostate; 8 patients were treated with hormones, 4 were treated with radiation, and 1 received both radiation and hormone therapy. Of the 12 men without a prior diagnosis of adenocarcinoma, 2 patients had received hormonal therapy for benign prostatic hyperplasia. Eight of 33 cases were pure squamous carcinomas. The remaining cases were adenosquamous carcinoma (n = 16), adenosquamous and urothelial carcinoma (n = 3), and adenosquamous carcinoma and sarcoma (n = 6). The squamous carcinoma component of these mixed cases averaged 40% of the tumor volume (range 5%-95%) and had a range of cytologic atypia (mild [n = 6], moderate [n = 17], severe [n = 10]). In the 25 cases with adenocarcinoma, the glandular component tended to be high-grade (Gleason grade >6 in 19 cases). Immunohistochemistry for prostate specific acid phosphatase and prostate specific antigen was positive in a large percentage of the adenocarcinomas (85% and 75%, respectively) and only very focally positive in 12% of the squamous carcinomas. 34 beta E12 was diffusely positive in >95% of the squamous carcinomas and only focally positive in <10% of the adenocarcinomas. Cytokeratins 7 and 20 did not differentiate the squamous and adenocarcinoma components. Follow-up was available on 25 of 33 cases, with the average survival being 24 months (range 0-63 months). Squamous differentiation in prostate cancer is uncommon, often but not necessarily arising in the setting of prior hormone or radiation therapy, and is associated with a poor prognosis. In addition to pure squamous cell carcinoma and adenosquamous cancer, other patterns may be seen. Whereas the adenocarcinoma component is typically high grade, the squamous component has a wide range of differentiation.

Postatrophic hyperplasia of the prostate in Japan: histologic and immunohistochemical features and p53 gene mutation analysis.

Postatrophic hyperplasia (PAH) is one of the patterns of prostatic atrophy but has been regarded as a precursor of prostatic cancer (PCA) because of its possible increase in proliferative activity compared with simple atrophy and morphologic mimicry of PCA. Radical prostatectomy specimens obtained from 28 patients with PCA were analyzed by histologic and immunohistochemical methods by using 34 beta E12 and Ki-67 as primary antibodies. Tissue from PAH, PCA, high-grade prostatic intraepithelial neoplasia (HGPIN), a possible precursor of PCA, and benign hyperplasia were microdissected and p53 gene mutations were examined by the polymerase chain reaction-single strand conformation polymorphism method followed by direct sequencing. Histologically, PAH consists of compactly arranged small acini with irregular atrophic-appearing contours, mimicking PCA. PAH lesions were detected in 7 (25%) of 28 cases with PCA: multifocal in 6 of 7 (85.7%) cases, maximum size of lesions ranged from 0.3 to 2.3 mm. Mild nuclear enlargement and small nucleoli were observed in all cases. Capsular or perineural invasion, crystalloids, and mitotic figures were not found in any case. Inflammatory changes and fibrosis near PAH were found in 100% and 71% of cases, respectively. PAH involved non-transition zone in all cases and occasionally involved transition zone. Forty-three percent of PAH lesions were in proximity (<2 mm) to PCA. None of the clinical and pathologic factors examined were correlated with the presence of PAH. Immunohistochemical analysis by using 34 beta E12 revealed intact basal cells. Proliferative activity defined by positive rate for labeling with MIB-1 antibody was intermediate between benign prostatic hyperplasia and HGPIN. The frequency of p53 mutations in PAH lesions was 5.3%, which was similar to that in HGPIN lesions (4.2%). Benign glands never showed mutations. These findings suggested that PAH might be a precursor for PCA.

Immunohistochemical analysis of clear cell carcinoma of the gynecologic tract.

Clear cell carcinoma of the gynecologic tract has been defined in terms of its clinical and histologic features; however, its immunophenotypic profile has not been fully characterized. Seventeen cases of primary clear cell carcinoma from various sites within the female genital tract (11 ovary, 5 uterus, 1 vagina) were analyzed by immunohistochemistry. These tumors were assessed for the expression of cytokeratin 7 (CK7), cytokeratin 20 (CK20), low and high molecular weight cytokeratin, (CAM5.2 and 34 beta E12, respectively), carcinoembryonic antigen (CEA), Leu-M1, vimentin, estrogen receptor (ER), progesterone receptor (PR), bcl-2, p53, HER-2/neu, and CA-125. The characteristic immunoprofile for all sites was positivity for CK7, CAM5.2, 34 beta E12, CEA, Leu-M1, vimentin, bcl-2, p53, and CA-125; variably positivity for ER and HER-2/neu; and negativity for CK20 and PR. For comparison, two cases of urologic clear cell carcinoma (1 bladder, 1 urethra) were also studied, and their profile was found to be similar to the gynecologic cases. Aside from minor differences, clear cell carcinoma appears to have the same immunophenotype regardless of whether it originates in the endometrium, ovary, or genitourinary tract. Much of its profile is similar to other gynecologic adenocarcinomas, but some of the markers studied may be useful in the differential diagnosis of this tumor.

The value of immunocytochemistry in distinguishing between clear cell carcinoma of the kidney and ovary.

Renal clear cell carcinoma rarely metastasizes to the ovary potentially mimicking a primary ovarian clear cell carcinoma. The immunocytochemical profiles of the two tumors were compared. Control groups of ovarian endometrioid and serous adenocarcinomas were also examined using the same antibody panel. Paraffin sections were studied with the immunocytochemical technique using eight antibodies. Renal clear cell carcinomas were positive for vimentin (8/12 cases), CK5/6 (0/12), 34 beta E12 (1/12), Ber-Ep4 (5/12), CA125 (0/12), ER (1/12), and PGR (1/12). Ovarian clear cell carcinomas showed positivity with vimentin (1/10 cases), CK5/6 (2/10), 34 beta E12 (10/10), Ber-Ep4 (10/10), CA125 (8/10), ER (7/10), and PGR (6/10). Endometrioid adenocarcinomas were positive for vimentin (9/10 cases), CK5/6 (8/10), 34 beta E12 (10/10), Ber-Ep4 (9/10), CA125 (9/10), ER (9/10), and PGR (10/10). Eight serous adenocarcinomas were positive in all cases for all the antibodies except CK5/6 (7/8 cases) and 34 beta E12 (7/8 cases). All the tumors reacted for epithelial membrane antigen. This immunohistochemical panel allows clear cell carcinomas of kidney and ovary to be distinguished. The latter has a greater phenotypic similarity with serous and endometrioid adenocarcinomas than with renal clear cell carcinoma demonstrating yet again that these ovarian tumors share a common histogenetic origin.

Minimal adenocarcinoma in prostate needle biopsy tissue.

One of the major diagnostic challenges in prostate needle biopsy interpretation is definitive establishment of a malignant diagnosis based on a minimal or limited amount of carcinoma in needle biopsy tissue. Major and minor diagnostic criteria should be used for interpretation of small foci of carcinoma. The constellation of findings and a combination of the major and minor diagnostic criteria permit a definitive diagnosis of focal adenocarcinoma. The differential diagnosis of minimal prostatic adenocarcinoma in needle biopsy tissue is broad and includes many benign lesions. The benign entities most likelty to be misdiagnosed as minimal prostatic adenocarcinoma are atypical adenomatous hyperplasia (adenosis) and atrophy. High-grade prostatic intraepithelial neoplasia and a descriptive diagnosis of focal glandular atypia or atypical small acinar proliferation also should be considered before diagnosing minimal adenocarcinoma. The most valuable adjunctive study for the diagnosis of minimal adenocarcinoma is immunohistochemistry using antibody 34 beta E12, reactive against basal cell-specific high-molecular-weight cytokeratins. Most cases can be diagnosed based on H&E-stained sections without this immunostain. Most minimal carcinomas in prostate needle biopsy tissue are of intermediate histologic grade, and most are indicative of pathologically significant carcinoma in the whole prostate gland.

Placental site nodules and plaques: a clinicopathological and immunohistochemical study of 25 cases with ultrastructural findings

Placental site nodules or plaques (PSN-Ps) are nodular benign lesions of the intermediate trophoblast (IT) cells in the endometrium, endocervix, superficial myometrium or fallopian tube, occurring after a remote intrauterine pregnancy. We present a study of 25 cases of PSN-Ps These lesions occurred in patients aged 18 to 44 years. Most were discovered incidentally in endometrial curettage specimens. The specimens were received as part of clinical investigations for menorrhagia, per vaginal bleeding or pelvic pain. None of the PSN-Ps was visible grossly. Microscopically, they were mostly multiple, well-circumscribed, oval or plaque-like cellular nodules. The IT cells typically had abundant vacuolated or eosinophilic cytoplasm. The nuclei were irregular, large, hyperchromatic, often degenerate-looking and either mononucleated, multinucleated or multiclefted. Hyalinization surrounding individual or groups of IT cells, or located in the centre of the nodules, was a constant feature in all cases. The lesional cells were strongly immunoreactive to CAM 5.2, 34 beta E12, AE1/AE3, EMA and vimentin. Some cases showed focal positivity to HCG and HPL. PLAP staining was consistently negative. Ultrastructurally, the IT cells showed prominent nuclear variation in size and shape. The abundant, vacuolated cytoplasm contained some rough endoplasmic reticulum and loosely arranged filaments. This study describes the clinicopathological and immunophenotypic features of 25 cases of PSN-Ps including the ultrastructural findings of one case.