Low Molecular Weight Cytokeratin Research Articles

Adenomyoepithelial tumours and myoepithelial carcinomas of the breast – a spectrum of monophasic and biphasic tumours dominated by immature myoepithelial cells

BackgroundAdenomyoepithelial tumours and myoepithelial carcinomas of the breast are primarily defined by the presence of neoplastic cells with a myoepithelial immunophenotype. Current classification schemes are based on purely descriptive features and an assessment of individual prognosis is still problematic.MethodsA series of 27 adenomyoepithelial tumours of the breast was analysed immunohistochemically with antibodies directed against various cytokeratins, p63, smooth muscle alpha-actin (SMA) and vimentin. Additionally, double immunofluorescence and comparative genomic hybridisation (CGH) was performed.ResultsImmunohistochemically, all the tumours showed a constant expression of high molecular weight cytokeratins (Ck) Ck5 and Ck14, p63, SMA and vimentin. With exception of one case diagnosed as myoepithelial carcinoma, all tested tumours expressed low molecular weight cytokeratin Ck18 in variable proportions of cells. Even in monophasic tumours lacking obvious glandular differentiation in conventional staining, a number of neoplastic cells still expressed those cytokeratins. Double immunofluorescence revealed tumour cells exclusively staining for Ck5/Ck14 in the presence of other cell populations that co-expressed high molecular weight Ck5/Ck14 as well as either low molecular weight Ck8/18 or SMA. Based on morphology, we assigned the series to three categories, benign, borderline and malignant. This classification was supported by a stepwise increase in cytogenetic alterations on CGH.ConclusionAdenomyoepithelial tumours comprise a spectrum of neoplasms consisting of an admixture of glandular and myoepithelial differentiation patterns. As a key component SMA-positive cells co-expressing cytokeratins could be identified. Although categorisation of adenomyoepithelial tumours in benign, borderline and malignant was supported by results of CGH, any assessment of prognosis requires to be firmly based on morphological grounds. At present it is not yet clear, if and to what extent proposed Ck5-positive progenitor cells contribute to the immunohistochemical and morphological heterogeneity of these neoplasms of the breast.

Interferon-γ induces neuroendocrine differentiation of in vitro cultivated human prostate basal epithelial cells

Prostatic neuroendocrine (NE) cells are intraglandular hybrid epithelial-neural-endocrine cells which express and secrete chromogranin, serotonin and numerous hormones and neuropeptides. Presumably NE cells regulate growth, differentiation and secretory activity of the prostatic epithelium through paracrine, endocrine and neurocrine mechanisms. They appear to differentiate from a common basal/precursor/stem cell which also gives rise to the secretory epithelium, but the responsible factors and mechanisms are still under investigation. The aim of this study was to evaluate the effects of type 1 (α, β) and type 2 (γ) interferons on human prostate basal cell (PrECs) proliferation and differentiation. Whereas α/β interferons increased the expression of the cell-cycle inhibitor p21CIP1 and inhibited DNA synthesis, IFN-γ led to increased apoptosis, cell-cycle inhibitor p27KIP1 expression and to differentiation of PrECs into NE-like cells. These morphological changes could neither be observed in stromal prostatic fibroblasts nor in prostate cancer cell lines LNCaP, PC-3 and BPH-1. In vitro differentiated NE-like cells expressed the glycolytic enzyme neuron-specific enolase (NSE) and chromogranin A (CgA), known markers of NE-cells in vivo in the prostate. Moreover, they changed their cytokeratin expression pattern by upregulating low molecular weight cytokeratins (LMW-CK) 8 and 18 found predominantly in terminally differentiated secretory luminal/NE epithelial cells. Thus, IFN-γ produced locally in the aging prostate by basal cells and under proinflammatory conditions by infiltrating lymphocytes might influence NE cell differentiation and function and favour NE differentiation of tumor cells in hormone-refractory prostate cancer.

S‐100 Protein Positivity in Merkel Cell Carcinoma: An Uncommon Finding

Merkel cell carcinoma (MCC) is a small round cell tumor which does not characteristically stain with S‐100 protein. We report a case of an 83 year‐old male with a two‐month history of an ulcerated nodule on the right arm. Histopathology revealed small blue round cells arrayed in a trabecular pattern and in diffuse sheets, with scattered mitoses and necrosis. The cells were negative for vimentin, positive for NSE, focally positive for high molecular weight cytokeratins and diffusely positive for low molecular weight cytokeratins, including CK20. The findings were diagnostic of MCC, however, foci of S‐100 protein positive cells were also present in the tumor. Upon reviewing cases from Skin Pathology Laboratory at BUSM received between 1/1/2000 to 7/30/2004, we documented a total of 34 cases diagnosed as MCC; 24 were stained with S‐100 protein and this case was the only one that stained positively. S‐100 protein positivity of MCC, while having been previously reported, is an uncommon finding. We report our case to stress the importance of morphological and immunoperioxidase features for the diagnosis of Merkel cell carcinoma, particularly in the exceptional cases which exhibit S‐100 protein positivity.

Hyaline Cell‐Rich Chondroid Syringoma‐ Report of Two Cases.

Case 1: A 38 year‐old man presented with a painless right post auricular mass, slowly growing for ten years. Clinical impression was a salivary gland lesion. The excised mass measured 3 cm and was gelatinous. Case 2: A 28 year‐old man presented with a lump in the region of the left heel, slowly growing for several years. Excision revealed a lobulated pink‐gray mass measuring 2 cm. In both cases, histology demonstrated a circumscribed encapsulated proliferation of tumour cells surrounded by abundant myxoid stroma. There were almost exclusively hyaline cells with plasmacytoid features, arranged predominantly in nests and sheets with abundant pink cytoplasm and hyaline inclusions. Round to oval nuclei with occasional small nucleoli and rare mitotic figures were seen. Both cases stained strongly positive for low molecular weight cytokeratin, S 100 and vimentin and were negative for desmin, smooth‐muscle actin and muscle‐specific actin. We describe two cases of hyaline cell‐rich chondroid syringoma, a histologically benign entity. The importance in recognizing this entity is that these tumors can easily be confused with malignant neoplasms including malignant melanoma, myxoid chondrosarcoma and alveolar soft part sarcoma. Follow up for a year has shown no evidence of metastases or recurrence in both cases.

Papillomas and carcinomas of the choroid plexus: histological and immunohistochemical studies and comparison with normal fetal choroid plexus.

Choroid plexus tumors are rare. Results on immunohistochemical features are scanty and controversial even regarding normal plexus. Thirteen cases of choroid plexus tumors and five samples of normal fetal choroid plexus were submitted to immunohistochemical study using a panel of epithelial, neuronal and stromal markers. Relevant histological findings were presence of clear cells in 3/5 papillomas (PP) and 7/8 carcinomas (CA) and all 5 fetal plexuses; rhabdoid cells, desmoplasia and vascular proliferation were found respectively in 3, 4 and 5 cases out of 6 poorly differentiated CA and were absent in PP and well differentiated CA. Pancytokeratin AE1/AE3 was strongly positive in all 13 cases, even in the undifferentiated component of poorly differentiated CA, where reactivity was focal in 3 and diffuse in 3 cases. Low molecular weight cytokeratin (35betaH11) was not expressed in any of the 8 CA, but was present in all 5 PP. In 4 of 6 poorly differentiated CA there was reactivity for smooth muscle actin (1A4) in 10 to 30% of the cells. This was true also for one case lacking rhabdoid cells. Laminin was undetectable in all 6 cases of poorly differentiated CA but was present in 4 PP and 2 well differentiated CA. All 5 fetal plexuses expressed GFAP.

Differential downregulation of αT-catenin expression in placenta: trophoblast cell type-dependent imprinting of the CTNNA3 gene

The αE-catenin is a well-known invasion suppressor. A recently described novel α-catenin, i.e. αT-catenin ( CTNNA3), shows related functions being necessary for the formation of cell–cell adhesion complexes. We recently demonstrated that the 10q21.3 region containing the CTNNA3 gene shows a parent-of-origin effect and that transcription of the CTNNA3 gene is downregulated in placental tissues of complete androgenetic origin. As this suggests that the CTNNA3 gene is subject to imprinting, we performed allele-specific RT-PCR on early placenta tissues using informative heterozygous samples. This was supplemented by immunostaining for αT-catenin, p57KIP2 and low molecular weight cytokeratin in tissues of a partial hydatidiform mole. As shown here we demonstrate that the CTNNA3 gene is subject to imprinting with preferential expression of the maternal allele in first trimester placental tissues. Imprinting, however, is trophoblast cell type-dependent: expression in extravillus trophoblast is biallelic; expression in villus cytotrophoblast is from the maternal allele only. Expression of αT-catenin is lost in villus syncytiotrophoblast as well as in extravillus trophoblast following epithelial–mesenchymal transition. The trophoblast cell type-dependent imprinting of CTNNA3 is identical to p57KIP2 imprinting with respect to trophoblast cell type (villus) and parental origin of the expressed allele (maternal). This suggests that gene dosage compensation of CTNNA3 and p57KIP2 in the placenta shares a conserved regulatory mechanism that correlates with an early step in trophoblast determination, i.e. differentiation into villus or extravillus trophoblast.

Fas expression in pancreatic adenocarcinoma is related to prognosis

9695 Background: Based on the histopathological assessment of pancreatic cancer resection specimens, prognostically relevant factors are known. However, the knowledge of additional factors associated with the prognosis might be helpful in planning the therapy for an individual patient. Methods: We investigated paraffin-embedded specimens of 25 patients undergoing surgical treatment for adenocarcinoma by immunohistochemistry to assess the expression and the prognostic impact of p53, Ki-67, Bcl-2, Fas and MMP-9. The number of positive neoplastic cells and the intensity of staining were scored semiquantitatively. The presence of micrometastases in locoregional lymph nodes was studied by staining for low molecular weight-cytokeratins. Neither survival time nor disease-free survival time were known at the time of the investigation. Results: No correlation was established between immunohistochemically detected micrometastases and prognosis.The expression of p53, Ki-67, Bcl-2 and MMP-9 did not influence the survival or disease-free survival. Expression of Fas, however, was associated with longer disease-free survival (P=0.014). Conclusions: Fas exerts an influence on prognosis in adenocarcinoma of the pancreas. However, further investigations in larger patient samples are required to confirm these results. No significant financial relationships to disclose.

Immunohistochemical and ultrastructural markers suggest different origins for cuboidal and polygonal cells in pulmonary sclerosing hemangioma

We report the morphological characteristics of 30 cases of sclerosing hemangioma (SH) of the lung and explore the histological origin of the major cells in these tumors. In addition to routine light and electron microscopy, immunohistochemistry was performed by using 12 monoclonal primary and 5 polyclonal primary antibodies. These included surfactant protein B (SP-B), thyroid transcription factor-1 (TTF-1), mast cell trypsin, CD68, epithelial antigen markers (high molecular weight cytokeratin, low molecular weight cytokeratin [CK-L], epithelial membrane antigen [EMA], cancer embryonic antigen), mesothelial antigen, neuroendocrine markers (neuron-specific enolase [NSE], chromogranin A, synaptophysin, calcitonin, adrenocorticotropic hormone, human growth hormone [hHG]), vimentin, and CD34. Surface cuboidal cells have short microvilli and have lamellar bodies in their cytoplasm. They can sometimes merge into multinuclear giant cells. Immunohistochemical results showed that these cells are strongly positive for SP-B, TTF-1, CK-L, EMA, and cancer embryonic antigen, whereas polygonal cells, previously also described as round or pale cells, were strongly positive for vimentin and TTF-1, and positive or weakly positive for 2 to 3 kinds of neuroendocrine markers. Sparse neuroendocrine granules and abundant microfilaments were observed in their cytoplasm. Some cell clusters in the solid regions were positive for SP-B and EMA. Mast cells existed sparsely in almost every field. Both cuboidal and polygonal cells were negative to CD34 and mesothelial antigen staining. We conclude that cuboidal cells of SH originate from reactive proliferating type II pneumocytes, which can fuse into multinuclear giant cells. Polygonal cells, as true tumor cells, likely originate from multipotential primitive respiratory epithelium and possess the capability for multipotential differentiation. The antibodies of SP-B, TTF-1, vimentin, and CK-L are very helpful to diagnosis and differential diagnosis of SH.

Combined effect of aloe-emodin and chemotherapeutic agents on the proliferation of an adherent variant cell line of Merkel cell carcinoma

Merkel cell carcinoma (MCC) has only limited sensitivity to chemotherapeutic agents. The aim of the study was to determine if members of the anthraquinone family could be used as adjuncts to increase the growth inhibiting effect of anticancer agents in MCC. An adherent variant of MCC was derived from a previously established MCC cell line suspension. Cells were characterized by immunocytochemical methods using specific antibodies against epithelial (low molecular weight cytokeratins and cytokeratin 20) and neuroendocrine (neuron-specific enolase, neurofilament protein, chromogranin A and synaptophysin) antigens. Emodin and aloe-emodin, members of the anthraquinone family, inhibited proliferation of the adherent MCC cells, with a slight advantage of aloe-emodin over emodin. Aloin had no effect on cell proliferation. The chemotherapeutic agents, cis-platinol (abiplastin), doxorubicin (adriablastin), and 5-fluorouracil, and the tyrosine kinase inhibitor STI 571, all independently inhibited the proliferation of adherent MCC cells. The addition of aloe-emodin potentiated their inhibitory effect, especially when low concentrations of the anticancer compounds were used. The antiproliferative action of STI 571 may be associated with the presence of anti-c-kit antibodies. The combined use of anticancer agents, especially at low concentrations, and aloe-emodin may be considered a preferable means for treating MCC.

Effects of eb virus encoded LMP1 on differentiation of nasopharyngeal carcinoma cells

Objective: To investigate the effects of Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1). expression on tumor cell differentiation in early-stage nasopharyngeal carcinoma (NPC). Methods: Thirty-one biopsies of early-stage NPC were collected from the Cancer Center, Sun Yat-sen University. All 31 NPCs were of non-keratinizing carcinoma in histological type. The Epstein-Barr virus early RNAs (EBERs) were detected by use of DAKO PNA Probe (Y5200) and PNA ISH Detection Kit (K5201). The LMP1, α-catenin, β-catenin, γ-catenin, high-molecular and low-molecular weight cytokeratins were detected by immunohistochemistry. Results: All 31 carcinoma biopsies studied showed a considerable number of EBERs-positive tumor cells, and 19 out of 31 cases (61.29%) expressed LMP1. The mean percentage of γ-catenin expression in LMP1 positive group (53.25±34.12%) was significantly lower than that (80.42±15.77%) in LMP1 negative group, (P<0.01). The γ-catenin expression was positively correlated with the expression of low molecular weight cytokeratin (r=0.440,P<0.05). There were positive correlations for the expression of α-catenin, β-catenin and γ-catenin in between. Conclusion: The LMP1 could down-regulate the expression of γ-catenin and thus inhibit the tumor cell differentiation in early-stage NPC.

Cytokeratin Immunohistochemistry: A Procedure for Exclusion of Pregnancy in Chorionic Villi-Negative Specimen

The confirmation or exclusion of the presence of products of conception (POC) in biological material may be crucial. This analysis has been undertaken to check how efficient the H&E examination of the putative POC specimen is in practice and to prove the hypothesis that the use of cytokeratin immunostaining can increase the diagnostic accuracy. Of 1078 POC specimens, 94 cases which were signed out as ‘No chorionic villi identified’ or ‘Negative for POC’ and in which all submitted material was histologically examined, were re-reviewed histologically and examined immunohistologically using the low molecular weight cytokeratin antibody CAM5.2. In six cases, the originally missed trophoblastic cells were found on re-review of the H&E slides, which was confirmed by CAM5.2 immunostaining. Of seven further cases which were suspicious for trophoblastic cells on re-review, three cases were positive for trophoblastic cells by CAM5.2 and four were negative. Of the remaining 81 cases negative for trophoblastic cells on H&E re-review, CAM5.2 was positive for the trophoblast in 13 (16 per cent). There were no false positive cases on CAM5.2 immunostaining of the endometrial curettings in 22 ectopic pregnancies and 22 cases with dysfunctional endometrial bleeding clinically and secretory endometrium histologically. Therefore, although the overall efficiency of the original diagnosis could have been as high as 98 per cent (1029 of 1051), the false negative rate was 23 per cent (22 of 94) in the chorionic villi-negative material. Even though the morphology of trophoblastic cells on conventional H&E staining is well known, it may be practically difficult to exclude pregnancy by the examination of uterine contents using conventional H&E staining only. The use of the cytokeratin immunostaining can decrease the rate significantly and should be considered in all chorionic villi-negative specimens without obvious extravillous trophoblasts.

Intermediate basal cells of the prostate: in vitro and in vivo characterization.

Progenitor cells within the prostate basal layer may play important roles in differentiation and carcinogenesis; however, prostate stem cell populations remain uncharacterized. Immunohistochemical and immunoblot analyses were used to characterize prostate epithelial cells (PrEC), a commercially available prostate basal cell isolate. Proliferating PrECs exhibited immunophenotypic characteristics most consistent with basal cells, but during senescence PrECs up-regulated androgen receptor (AR) mRNA, p27, and low-molecular-weight cytokeratin (LMWCK) expression, suggestive of partial differentiation. PrECs also stained strongly for involucrin, which marked a subset of intermediate prostate basal cells in vivo. Basal hyperplasia consisting of involucrin-positive cells was prevalent in prostate tissue from androgen-ablated patients, and formed epithelial clusters flanked by involucrin-negative basal and luminal monolayers. Cultivation of PrECs on matrigel together with androgen-treated stromal conditioned media resulted in dense aggregates, with a peripheral rim of basal-like cells expressing p63 and basal cytokeratins. PrEC represents an epithelial population whose basal characteristics are modified in response to matrigel, stromal factors, and senescence, consistent with a transient amplifying population. These cells may derive from a previously unrecognized, involucrin-positive subset present in vivo.

Cytokeratin 7 and 20 expression in epithelioid sarcoma.

Epithelioid sarcoma (ES) is a rare malignant soft tissue tumor of uncertain histogenesis that arises predominantly in the extremities of young adults. Immunohistochemically, the neoplastic cells are typically positive for vimentin, low molecular weight cytokeratin (CAM5.2) and epithelial membrane antigen (EMA). We examined eight cases of ES from seven different patients. All cases were studied with immunohistochemistry for EMA, CAM5.2 (keratin 8 and 18), 34BE12 (keratins 1, 5, 10 and 14/15), cytokeratins 7 and 20 (CK7, CK20), and CD34. The average patient age was 53 (range 43-76) and the male:female ratio was 5:2. The location was the upper extremity in five tumors, the lower extremity, the perineum, and the paraspinal soft tissue in one tumor each. All cases contained predominantly epithelioid cells, but spindle cells were also present in three cases. All cases contained areas of geographic necrosis. CAM5.2 was strongly positive in seven tumors and focally positive in one (8/8). EMA was diffusely positive in two cases and focally positive in five cases (7/8). CD34 was diffusely positive in 3/8 cases. 34BE12 was diffusely positive in one case and focally positive in two others (3/8). CK7 was diffusely positive in one case and focally positive in another (2/8). CK20 was negative in all cases (0/8). All cases tested were positive for vimentin (6/6), 2 cases were focally positive for HHF35 (2/5), and all cases tested were negative for S-100 protein (0/7). In addition to the known immunoreactivity for CAM5.2 and EMA, there is positivity for CK7 and 34BE12 in a small proportion of cases. None of the cases expressed CK20. This immunophenotypic profile suggests that ES is more similar to carcinoma and synovial sarcoma than to other soft tissue tumors, and may be of diagnostic utility.

Hepatoid adenocarcinoma of the urinary bladder.

Hepatoid adenocarcinoma is rare in the urinary bladder with only three well-illustrated previously reported cases. Pathological diagnosis is based on a combination of histological features resembling hepatocellular carcinoma and the positive immunostaining for alpha-fetoprotein. We present the clinicopathological features of four additional cases. The patients were males 66, 85, 61 and 68 years old. Hematuria was the initial symptom in all four patients. Two cases were treated by cystoprostatectomy and the remaining two by transurethral resection of the bladder. On histology, the cases showed a mixture of cells growing in a solid fashion and sheets or anastomosing trabeculae of hepatoid cells merging focally with a secondary glandular pattern of adenocarcinoma. Intracytoplasmic hyaline globules in all and bile production in three of the cases also supported the impression of hepatocytic differentiation. Immunoreactivity for alpha-fetoprotein, low molecular weight cytokeratin, alpha-1-antitrypsin, albumin, epithelial membrane antigen and a striking canalicular pattern when stained against polyclonal carcinoembryonic antigen (CEA), all indicate hepatocellular differentiation. The hepatic nature of the cells was further assessed by detecting the recently incorporated marker hepatocyte paraffin 1, by means of immunohistochemistry and albumin gene mRNA non-isotopic in situ hybridization, both of which had positive signals in all four cases. Three patients died 12, 14 and 19 months after diagnosis. The fourth patient was alive with disease at 26 months of follow-up. In conclusion, hepatoid adenocarcinoma seems to be an aggressive malignant neoplasm that is rare in the bladder whose correct diagnosis may need appropriate immunohistochemical and in situ hybridization means in addition to a complete patient clinical and pathological evaluation. The exact histogenesis and classification of these tumors remains to be established.

Histiocytoid variant of eccrine sweat gland carcinoma of the eyelid and orbit: report of five cases

ObjectiveTo study the clinicopathologic features of the histiocytoid variant of adenocarcinoma of the eccrine sweat gland of the eye and orbit. DesignRetrospective case series. ParticipantsFive patients undergoing orbital and eyelid biopsy as a diagnostic procedure. MethodsThe authors examined the clinical histories and pathologic findings of five patients with eccrine adenocarcinoma of the eyelid with orbital invasion. Main outcome measuresClinical and histopathologic examinations, including routine histopathology, immunohistochemistry, and electron microscopy studies. ResultsThe tumors presented as insidious, diffusely infiltrative, firm cutaneous masses in the periocular area that later infiltrated the orbit. Histopathologic examination revealed that the tumors infiltrated the dermis and were composed of cells with a histiocytic to signet ring appearance. Tumor cells exhibited intracellular mucin production. Immunohistochemical stains were positive in tumor cells for low and high molecular weight cytokeratins, carcinoembryonic antigen, and epithelial membrane antigen. Electron microscopic examination showed lumen formation and intracytoplasmic mucin in tumor cells. ConclusionsThe histiocytoid variant of adenocarcinoma of the eccrine sweat gland of the eyelid may present as an insidious tumor and diffusely invade the orbit. These cases may be confused with metastatic adenocarcinoma.

Diagnostic and Pathogenetic Implications of Colorectal Carcinomas with Multidirectional Differentiation: A Report of 4 Cases

Multidirectional differentiation in colorectal carcinomas is a rare phenomenon. Four cases are reported herein, and their clinical and pathologic characteristics are discussed. Two men and 2 women between the ages of 56 and 76 years who presented with abdominal symptoms are included in this report. Two tumors were located in the right colon, one in the splenic flexure, and one in the descending colon. Distant metastases were evident at presentation in 3 of 4 cases. Histologically, two tumors exhibited neuroendocrine and glandular differentiation; the third tumor was an adenocarcinoma with a sarcomatous component and the fourth tumor showed 3 lines of differentiation (glandular, squamous, and sarcomatoid). In all tumors evaluated, areas of adenocarcinomas were positive for low-molecular weight cytokeratin (CAM 5.2) and mucicarmine, but negative for high-molecular weight cytokeratin (AE3). The squamous cell component was AE3 positive and CAM 5.2 negative. The neuroendocrine component was highlighted by neuroendocrine markers and the sarcomatoid component revealed smooth muscle differentiation. All tumors (except one mucinous tumor) were negative for cytokeratin-20 staining. One patient was on supportive care for terminal metastatic carcinoma, and 2 patients were being treated with adjuvant chemotherapy at the time of this report. Colon carcinoma with multidirectional differentiation is a rare event and may originate from stem cells within the gastrointestinal mucosa, and/or represent the convergence of multiple tumors arising at the same site. This type of tumor should be considered in the differential diagnosis of a bowel biopsy with multiple histopathologic variants.

Intracellular distribution of intermediate filaments in vimentin-positive gastric carcinomas: confocal laser scanning microscopy using formalin-fixed paraffin-embedded specimens.

Intermediate filaments are known as cytoskeletal elements. Recently, additional vimentin expression has been reported in some carcinomas; however, the function of such expression remains unclear. We studied the intracellular distribution of low-molecular weight cytokeratin and vimentin by immunohistochemistry in 17 vimentin-positive gastric carcinomas using confocal laser scanning microscopy. All materials were formalin-fixed and paraffin-embedded. Low-molecular weight cytokeratin expression showed a membranous pattern with a prominent deposition just below the cytoplasmic membrane in both tubular and solid components of the carcinomas. This unique membranous deposition was frequently absent in diffuse components. On the other hand, vimentin expression showed a fibrillary pattern in all components and also showed a unique basal distribution in the tubular components. We also recognized an aggregate pattern of the intermediate filament expression in diffuse components. We conclude that the significance of vimentin expression in carcinoma cells cannot be explained as a simple substitution for low-molecular weight cytokeratin because the distribution of vimentin and low-molecular weight cytokeratin is different.

巣状にへん平上皮癌への分化を伴った下顎歯肉原発複合型大細胞神経内分泌癌の１例

An extremely rare case of combined large cell neuroendocrine carcinoma of the lower gingiva associated with focal differentiation to squamous cell carcinoma is presented. Travis et al. proposed a new, distinctive clinicopathologic type of pulmonary neuroendocrine tumor, termed large cell neuroendocrine carcinoma(LCNEC). It is defined as a poorly differentiated, high-grade neuroendocrine tumor that has morphologic and biologic features intermediate between atypical carcinoid and small cell carcinoma.A 59-year-old man presented with bleeding and swelling of the lower gingiva. The pathological diagnosis of a biopsy specimen was poorly differentiated squamous cell carcinoma. The patient therefore underwent surgical resection of the tumor.The tumor was composed of larger cells than those of small cell carcinoma and exhibited solid, trabecular, and slightly rosette-like growth patterns with a high mitotic rate in normal subepithelial interstitial tissue. Grimelius staining was positive, and chromogranin A and neural cell adhesion molecule (CD56)immunostaining was positive. The tumor was diagnosed as large cell neuroendocrine carcinoma on microscopic and immunohistochemical studies.On hematoxylin and cosin staining, there were no signs of transition between neuroendocrine carcinoma and carcinoma in situ. However, at the circumference of neuroendocrine carcinoma, a mass of cells associated with differentiation to squamous cell carcinoma was seen. These cells showed positive CAM5.2(lowmolecular-weight cytokeratin)immunostaining. Therefore, the tumor was finally diagnosed as a combined large cell neuroendocrine carcinoma of the lower gingiva associated with focal differentiation to squamous cell carcinoma.

CONGENITAL PREPUBIC SINUS: A VARIANT OF DORSAL URETHRAL DUPLICATION SUGGESTED BY IMMUNOHISTOCHEMICAL ANALYSIS

Congenital prepubic sinus is a rare disorder of uncertain etiology. Immunohistochemical staining is used to elucidate the etiology of the sinus. We treated 5 patients with congenital prepubic sinus. A sinogram delineated the tract, which was then excised. In addition to routine hematoxylin and eosin stain of the 5 specimens, immunohistochemical analysis was also performed with smooth muscle and sarcomeric actin, high (34betaE12) and low molecular weight cytokeratin (35betaH11), and cytokeratin 7 antibodies. The 2 females and 3 males were 1 month to 14 years old. All patients had presented with purulent discharge from the sinus opening. Hematoxylin and eosin stain demonstrated transitional and squamous epithelium lining the sinus. Immunohistochemical study showed that the stain with 3 cytokeratin antibodies was moderately to strongly positive in all patients at the proximal end, low molecular weight cytokeratin weakly to moderately positive and cytokeratin 7 weakly positive to negative in 4 at the distal end. The results suggested that the lining epithelium was transitional proximally and squamous distally. An exception was a female patient who had the shortest tract lined with squamous epithelium only. Furthermore, smooth muscle but not sarcomeric actin demonstrated smooth muscle bundles around the sinus tract in 4 patients. The existence of transitional epithelium in the proximal part of the sinus and presence of smooth muscle bundles around it reinforce the theory that congenital prepubic sinus is a variant form of dorsal urethral duplication.

CD34 positive stromal cells in gastric adenocarcinomas

To investigate the role of CD34 positive stromal cells, namely dendritic interstitial cells, in gastric carcinomas, the distribution of CD34 positive stromal cells in gastric adenocarcinomas (GCs), with special reference to two histological types (diffuse (D-type) and intestinal (I-type)), was examined. In total, 55 surgically resected GCs (15 D-type and 40 I-type) and their normal tissues were examined. To distinguish CD34 positive stromal cells from vascular endothelial cells and to recognise the tumour border, immunostaining for CD34, CD31, and low molecular weight cytokeratins was performed. In the 15 D-type GCs, eight of the nine D-type GCs invading the muscularis propria and subserosa had a large number of CD34 positive stromal cells in the tumour stroma, whereas all six D-type GCs confined to the submucosa had no CD34 positive stromal cells in the tumour stroma. All of the 40 I-type GCs had no CD34 positive stromal cells, regardless of tumour depth. These results suggest that CD34 expression in stromal cells is associated with progression of D-type GCs, and that absence of expression is also seen in I-type GCs that are progressing.