Adenomatoid tumor of the adrenal gland: case report with immunohistochemical study

Adrenal adenomatoid tumor (AT) is a recently recognized disease with marked male predominance. Herein is presented a case of adrenal AT incidentally found in a 30-year-old man and results of immunohistochemical examination of the tumor. The left adrenal gland, weighing 17 g, contained a mass measuring 3 x 2.5 x 2.5 cm in the cortical tissue. Cut surface showed a relatively well-circumscribed firm tumor with a white solid appearance. Histologically, the tumor had the typical appearance of AT described in the genital tract. Immunohistochemically, the tumor cells were positive for calretinin, D2-40, WT1, mesothelial cell antigen, CA125, thrombomodulin, vimentin and cytokeratins (stained by AE1 + AE3, OV-TL 12/30, CAM5.2 and MNF116), and negative for endothelial markers (CD31, CD34 and factor VIII-related antigen) and CD56. CD56-positive adrenocortical cells were diffusely scattered in the tumor, especially in its periphery. Immunohistochemistry of estrogen, progesterone and androgen receptors was negative. These findings confirm mesothelial origin of the tumor and suggest that this tumor has little relation to sex hormone despite male predominance.     

Superficial myofibroblastoma of the lower female genital tract: A clinicopathological analysis of 15 cases

ObjectiveTo describe the clinicopathological features and differential diagnoses of 15 cases of superficial myofibroblastoma, a rare mesenchymal tumor involving the lower female genital tract.MethodsThe clinicopathological data and immunohistochemical findings were retrospectively analyzed in 15 cases of superficial myofibroblastoma. Meanwhile, a systematic literature review was conducted.ResultsThe age of patients ranged from 34 to 73 years (median, 49 years). Most patients presented with nodular or polypoid masses ranging in size from 0.4 cm to 6.5 cm. Twelve tumors were located in the vagina, two in the vulva, and one in the cervix. Microscopically, the tumor was located in the subepithelial tissue, with a clear boundary and without capsule on the surface. The tumor cells were spindle, oval, stellate or wavy, and arranged in various architectural patterns of reticular, fascicular, wavy and disorderly patterns. There were no obvious cellular atypia and mitotic figures. Thin collagen fibers and thin-walled vessels could be observed in all cases. Most cases were diffusely and strongly reactive to Vimentin (12/12), Desmin (14/15), ER (15/15) and PR (13/14). Variable immunoreactivity for CD34 (8/15), Caldesmon (2/8), SMA (4/14) and CD99 (4/5) were observed. The tumors showed a low Ki67 proliferative index (≤5 %). Follow-up information was available in 10 patients and there was no evidence of recurrence or metastasis.ConclusionsSuperficial myofibroblastoma is a rare benign tumor that originates from the hormone-sensitive, subepithelial mesenchymal tissue of the lower female genital tract, and should be differentiated from other mesenchymal tumors.     

Circulating immunoglobulin A- and immunoglobulin G-secreting hybridoma cells in peripheral blood preferably migrate to female genital tracts. The role of sex hormones

Antigen-specific circulating immunoglobulin-secreting cells (ISC) migrate to various secondary and tertiary lymphoid tissues. To understand the migration of the cells into the genital tract and its regulation by sex hormones, spleen-derived SG2 hybridoma cells secreting immunoglobulin G2b (IgG2b) and Peyer's patch-derived PA4 hybridoma cells secreting polymer IgA were labelled with 3H-TdR, and intravenously injected into syngeneic mice of both sexes. Using flow cytometry, surface molecular markers of plasma cells, CD38 and CD138, and adhesion molecules, CD49d, CD162, and CD11a were found to be positive in SG2 and PA4 cells, but CD62L, alpha4beta7 and CD44 were not expressed on these cells. The relative distribution indexes (RDIs) of the cells in genital tract and other tissues were measured. The means of RDIs of SG2 and PA4 cells in female genital tissues were 6.5 and 4.5 times as many as the means in male genital tissues, respectively. The treatment of ovariectomized mice with beta-oestradiol significantly increased the RDIs of PA4 cells in cervix and vagina, but decreased the RDIs of SG2 cells in vagina, horn of uterus, uterus and rectum (P<0.05). Progesterone treatment increased the RDIs of PA4 cells in vagina and rectum (P<0.05). The treatment with testosterone significantly increased the RDIs of SG2 and PA4 cells in epididymis and accessory sex glands (P<0.05). These results demonstrate that the female genital tract is the preferable site for the migration of circulating hybridoma cells to the male genital tract, and sex hormones play an important role in regulation of the migration of circulating ISC to genital tracts.     

Angiomyofibroblastoma of the vulva: a large pedunculated mass formation

Angiomyofibroblastoma is a rare, usually small benign mesenchymal tumor that occurs in vulvar lesions of premenopausal women. A case of angiomyofibroblastoma that arose as a unique pedunculated and particularly large mass in the left vulva of a 48-year-old woman is presented herein. The patient had been aware of a gradually enlarged mass of 7 years duration without any other gynecological symptoms or signs. The maximum dimension of the tumor measured 11 cm. The resected tumor was well circumscribed with a bulging and glistening cut surface. Histological examination revealed an admixture of irregularly distributed hypercellular and hypocellular areas with spindled, plump spindled, or plasmacytoid stromal cells and abundant venular or capillary-sized vessels. Stromal cells characteristically cluster around delicate vessels within an edematous to collagenous matrix. In the present case, intralesional adipose tissue was present throughout the tumor. There was no significant nuclear atypia, and mitotic figures were very sparse. There was little stromal mucin throughout the tumor. Immunohistochemically, the stromal cells were characterized by strong reactivity for vimentin and CD34, with focal reactivity for desmin and alpha smooth muscle actin. Both estrogen and progesterone receptors were diffusely expressed in the stromal cells. These histological findings are consistent with angiomyofibroblastoma and support the hypothesis that angiomyofibroblastoma originates from perivascular stem cells with a capacity for myofibroblastic and fatty differentiation.     

Expression of Toll‐like Receptors in Genital Tract Tissues from Normal and HIV‐infected Men

Citation Pudney J, Anderson DJ. Expression of Toll‐like receptors in genital tract tissues from normal and HIV‐infected men. Am J Reprod Immunol 2011; 65: 28–43 Problem Cells of the innate immune system use Toll‐like receptors (TLRs) to recognize and respond to invading pathogens. This study was carried out to characterize TLR expression in the human male genital tract, an initial infection site for several sexually transmitted pathogens. Method of Study Immunohistochemistry was used to detect expression of TLRs 1–9 in genital tract tissues from HIV^? and HIV⁺ men. Results In HIV^? men, TLR1⁺ leukocytes were detected throughout the genital tract. Leukocytes in the penile urethra also expressed TLRs2, 3, 5, 7 and 9. Epithelial cells in most tissues did not express TLRs; exceptions were the prostate, where TLRs3 and 8 were observed on the apical surface of luminal epithelial cells, and the penile urethra, where epithelial cells expressed TLR9. In genital tissues from HIV⁺ men with AIDS, few TLR⁺ cells were detected. Conclusion Cells in the male genital tract can express a variety of TLRs. The penile urethra contained the highest number of TLR⁺ cells, indicating that this tissue plays a major role in the innate immune defense of the male genital tract. Overall, TLR expression was reduced in genital tissues from HIV⁺ men.     

The mucosa of the male genital tract; part of the common mucosal secretory immune system?

The selective migration of mucosal-derived lymphoid blasts to other mucosal organs is taken to be an essential part of the common secretory immune system. In rats, proliferating lymphoid cells from mesenteric lymph nodes (mLN) and peripheral lymph nodes (pLN) were labeled in vitro using two different techniques, in order to test the hypothesis that the mucosa of the male genital tract is a preferential site for mLN lymphoid blasts to home to. A low but significant migration to male genital organs was found, but with no difference between blasts from pLN and mLN. Thus there is no evidence to include the male genital tract in the common mucosal secretory immune system. Recirculating lymphocytes from the thoracic duct entered the male genital organs with a similar distribution to the pattern of lymphoid blasts. There is probably an exchange between these immigrating lymphocytes and the different subsets, which are localized in the epithelium (T suppressor) and interstitial tissue (T helper) in male genital organs. The lymphoid cells in the male genital tract might play an important role in the immune function of seminal fluid and in sexually transmissible diseases.     

血管肌纤维母细胞瘤16例临床病理分析

目的探讨血管肌纤维母细胞瘤（angiomyofibroblastoma,AMF）的临床病理、免疫组化特征、组织来源以及鉴别诊断。方法通过16例AMF的临床表现、病理形态和免疫组化研究,并结合文献复习,总结AMF的临床病理、免疫组化特征及鉴别诊断。结果16例AMF,大体境界清楚,无包膜,可见一层假纤维膜包绕;组织学上呈疏松水肿样,丰富薄壁海绵样血管,肿瘤细胞多样性,梭形及上皮样细胞多见,常围绕血管排列呈疏密交替分布特征。免疫组化结果：瘤细胞desmin及vimentin呈弥漫强阳性表达,actin、CD34、ER和PR染色稍弱、呈灶状分布,而S-100蛋白、NF和CK均阴性。结论AMF临床上多无明显症状;发病部位以女性外阴及盆腔最多见,但全身多处部位也可见;其生物学行为及组织来源尚无定论;术前很难确定诊断AMF,需与侵袭性血管黏液瘤、富于细胞性血管纤维瘤等相鉴别。     

The infecting dose of Chlamydia muridarum modulates the innate immune response and ascending infection

Murine vaginal infection with the obligate intracellular bacterium Chlamydia muridarum is commonly used as a model for ascending Chlamydia infections of the human female genital tract. Gamma interferon-producing Th1 cells, in concert with other mononuclear infiltrates, primarily mediate antichlamydial immunity. However, many factors modify this response, including the bacterial load. To investigate the manner in which the inoculating dose of C. muridarum modulates a genital infection, we measured innate and adaptive cell numbers, CD4+ lymphocyte cytokine profile, chemokine expression, course of infection, and pathological sequelae in genital tracts of BALB/c mice infected with doses of C. muridarum ranging from 10(4) to 10(7) inclusion-forming units. We found that the influx of both innate and adaptive immune cells responded similarly in the lower genital tract (cervical-vaginal tissues) and upper genital tract (oviduct tissues) to increasing inoculating doses. However, cells expressing the innate markers Gr-1 and CD11c were affected to a greater degree by increasing dose than lymphocytes of the adaptive immune response (Th1, CD4+, CD8+, CD19+), resulting in a change in the balance of innate and adaptive cell numbers to favor innate cells at higher infecting doses. Surprisingly, we detected greater numbers of viable chlamydiae in the oviducts at lower inoculating doses, and the number of organisms appeared to directly correlate with hydrosalpinx formation after both primary infection and repeat infection. Taken together, these data suggest that innate immune cells contribute to control of ascending infection.     

Toll-Like Receptors, Inflammation and Tumor in the Human Female Reproductive Tract

Abstract  Toll-like receptors are an important family of pattern recognition receptors. They recognize microbial conserved components and trigger protective responses to the invading pathogens, which constitute a major part of the innate immune system. Toll-like receptors are mainly expressed in immune cells. The current evidences demonstrate that Toll-like receptors are present in some epithelial cells and epithelium derived tumor cells. The expression of Toll-like receptors in these cells is related to infection and inflammation, and tumor progression as well. Genital mucosal epithelium is the first line in defense of microorganism invasion in the female reproductive tract. Toll-like receptors expressed in the genital tract have been implicated in many aspects of reproductive physiology and pathology in the female. In the current review, we will focus on the expression of Toll-like receptors in the female genital mucosa and its association with anti-infection immunity and tumorigenesis.     

Immunohistochemical analysis of carcinomatous and sarcomatous components in the uterine carcinosarcoma: a case report

Uterine carcinosarcoma (malignant mixed Mullerian tumor) is an uncommon female genital tract neoplasm characterized by an admixture of epithelial and stromal malignant cells. We report a case of 50-year-old peri-menopausal woman diagnosed to have early-stage (IB due to FIGO) uterine carcinosarcoma of the homologous type with superficial (3mm) myo-invasion. The patient showed no clinical symptoms of the disease and had no family history of female genital tract malignancies. Positive immunostaining for steroid receptors (estrogen-alpha and progesterone receptors), cytokeratin, and EGFR was detected only in the carcinomatous area, whereas beta-catenin, BCL-2, COX-2, p16(INK4a), PTEN, RB-1, and vimentin were immunoreactive in both components. Androgen receptor, CD10, desmin, HER-2/neu, and P53 were found to be negative either in the carcinomatous or in the sarcomatous area. Tumor proliferative activity was higher in the carcinomatous (25%) than in the sarcomatous (2%) component. Based on these findings, immunohistochemical evaluation of multiple receptor status in the carcinomatous and sarcomatous areas of carcinosarcoma may provide a clue to the pathogenesis and hormonal receptor status of this uncommon uterine malignancy.     

ADENOMATOID TUMOR OF THE MALE GENITAL TRACT–A Pathological Study of Eight Cases and Review of the Literature–

Eight cases of adenomatoid tumors of the male genital tract are presented. Histological, histochemical, and electron microscopic studies were performed and an approach to a new classification of adenomatoid tumors was discussed. The number of so-called adenomatoid tumors of male genital tract reported in Japan adding our eight cases totalled 60 cases. These were classfled as follows; 10 cases of mesothelial (superficial) type and 50 cases of adenomatoid (profound) type. Besides these, 8 cases of mesothelial type were reported in foreign literatures. Three cases of adenomatoid tumors of the uterus and a case of epididymitis chronica with reactive proliferation of mesothelial cells were also examined. As a result of these investigations, it is suggested that the histoQenesis of the so-called adenomatoid tumors is composed of two different processes: i.e., mesothelial type arising from serosal mesothelial cells and adenomatoid type arising from immature Miillerian mesenchymal tissue.     

血管肌纤维母细胞瘤临床病理特征

目的：探讨血管肌纤维母细胞瘤的临床病理形态特征及鉴别诊断。方法：对2例血管肌纤维母细胞进行组织病理学、免疫组织化学研究,结合文献资料分析本病的临床表现、病理形态特点及鉴别诊断。结果：血管肌纤维母细胞瘤呈大片黏液背景、丰富薄壁海绵样血管和梭形上皮样细胞即肌纤维母细胞,后者胞质丰富,呈嗜酸性,核卵圆或杆状,两端对称变细或稍钝,瘤细胞分布有明显的疏密区,密集区聚于血管周围,成束或链状排列、疏松区弥散于黏液背景中,且瘤细胞常与胶原纤维伴行。结论：血管肌纤维母细胞瘤为良性肿瘤,好发于女性外生殖器,起源与肌纤维母细胞相关,既向纤维,又向平滑肌分化,且伴有丰富的海绵样薄壁血压和间质黏液变性。     

子宫内膜间质肉瘤9例临床病理分析

目的 探讨子宫内膜间质肉瘤(endometrial stromal sarcoma,ESS)的临床病理特征、诊断、鉴别诊断及预后.方法 对9例ESS患者进行临床、病理资料分析、免疫组化检测及随访.结果 患者年龄39～64岁,中位46.3岁.临床主要表现为阴道流血及子宫增大/占位.肿瘤直径2.3～11 cm,平均4.6 cm.光镜下8例呈低度恶性子宫内膜间质肉瘤(low grade endometrial stromal sarcoma,LGESS),均由类似增殖期子宫内膜间质肿瘤细胞构成,细胞密集,异型性不明显,呈不规则舌状或岛状浸润肌层,并伴较多薄壁螺旋小血管;1例为高度恶性子宫内膜间质肉瘤/未分化子宫内膜肉瘤(high grade endometrial stromal sarcoma/undifferentiated endometrial sarcoma,HGESS/UES),肿瘤细胞直接替代子宫肌层,具有明显的细胞异型性,无LGESS常见的螺旋小血管.免疫组化检测显示肿瘤细胞CD10、vimentin均阳性,PR、ER大部分阳性,SMA和desmin及h-Caldesmon为极少数局灶阳性,S-100、CD34均阴性.术后随访7例(平均53个月),只有1例HGESS/UES死亡.结论 ESS是女性生殖道很少见的一种恶性肿瘤,恶性度相差很大.确诊主要依靠其临床病理特点,并辅以免疫组化标记综合分析.诊断时要与子宫内膜间质结节、平滑肌肿瘤、低分化癌等鉴别.     

T淋巴母细胞淋巴瘤/白血病的临床病理研究

目的 分析和总结T淋巴母细胞淋巴瘤/白血病(T-LBL/ALL)的临床、组织学、免疫表型特征,以提高对T-LBL/ALL的认识和诊断水平.方法 采用HE、免疫组织化学(EliVision法)、原位杂交及聚合酶链反应等方法结合临床资料对128例T-LBL/ALL进行了分析.结果 男94例,女34例.男女比2.8:1.年龄4-88岁,平均27岁,中位年龄22岁.58例病变累及淋巴结,27例累及淋巴结外,43例淋巴结内外均有累及.其中73.3%(74/101)累及颈部淋巴结,42.6%(43/101)累及纵隔.病变以弥漫为主,少数呈结节状.多数病例的瘤细胞为中小细胞,少数瘤细胞较大.瘤细胞表达末端脱氧核苷酸转移酶(TdT,94.5%,121/128)、CD34(49.0%,48/98)、CD3(72.2%,78/108)、CD7(96.3%,104/108)、CD43(88.9%,56/63)、CD79a(7.1%,5/70)、CD10(32.9%,25/76)、CD99(96.7%,58/60)、Pax-5(4.4%,4/91);128例髓过氧化物酶(MPO)均为阴性.共随访51例(39.8%),随访时间1～53个月.总体存活率68.6%;总体中位生存时间12个月.不同年龄组中CD3阳性率差异有统计学意义,30岁以上的病例CD3阳性率显著降低.CD10阳性患者的生存时间较阴性患者的生存时间短.5例T细胞受体(TCR)基因重排检测结果显示,4例有TCR基因克隆性重排.结论 T-LBL/ALL主要发生于青少年,以颈部淋巴结肿大和(或)纵隔肿物为主要临床表现.多数病例的肿瘤细胞以中小细胞为主,弥漫分布,但是也应注意到少数病例细胞较大,或结节状生长.免疫组织化学CD7、Pax-5、TdT、CD34、Ki-67五项抗体的联合应用有助于大多数病例确诊.对极少数病例可辅以TCR基因重排检测.     

Osteoclast-rich undifferentiated carcinomas of the urinary tract.

Osteoclast-like giant-cell neoplasms of the urinary tract are rare. They are composed of ovoid or spindle-shaped mononuclear cells with evenly spaced osteoclast-like giant cells. Terminology, histogenesis, and biologic behavior of these tumors remain controversial. Six cases of osteoclast-like giant-cell neoplasms of the urinary tract were identified from the consultation files of two of the authors. Patients were all male and elderly (range 65-82), with the exception of one 39-year-old male. In all, 3/6 tumors developed in the bladder and 3/6 in the renal pelvis. Size ranged from 5 to 11 cm. One bladder and three renal pelvis tumors were high stage (pT3) at time of presentation. Adjacent to the osteoclast-like giant-cell neoplasm in the same specimen, all patients had urothelial carcinoma in situ and/or high-grade papillary urothelial carcinoma. Multinucleated cells had identical morphological and immunohistochemical properties of osteoclasts; positive for CD-68, LCA, CD51 and CD54, and negative for cytokeratins and EMA. Varying percentages of mononuclear cells expressed alpha-smooth muscle actin (4/6), desmin (1/6), S-100 (4/6), LCA (2/6) and CD68 (6/6). However, mononuclear cells were also positive for epithelial markers in 4/6 tumors (cytokeratins AE-1/AE-3, Cam 5.2, CK7 and/or EMA). p53 stained mononuclear tumor cells in three cases, paralleling the staining on the accompanying urothelial carcinoma. Ki-67 stained mononuclear tumor cells, but not osteoclast-like giant cells. Follow-up data were available in five cases. One patient developed recurrence of noninvasive urothelial carcinoma and is still alive. Four patients were dead due to disease within 15 months, three with distant metastases. The intimate association of these tumors with urothelial carcinoma along with their immunohistochemical profile supports an epithelial origin for the mononuclear cells and non-neoplastic reactive histiocytic lineage for the osteoclast-like giant cells.     

CD4+ T cells play a significant role in adoptive immunity to Chlamydia trachomatis infection of the mouse genital tract.

The ability of CD4+ and CD8+ T cells to adoptively immunize mice against Chlamydia trachomatis infection of the mouse genital tract was studied. Adoptive transfer experiments were performed with splenic CD4+ or CD8+ T cells obtained from mice following resolution of a primary genital tract infection and after a secondary chlamydial challenge. The results show that donor CD4+ T cells, but not CD8+ T cells, obtained from mice following resolution of a primary infection or after secondary challenge were effective in transferring significant antichlamydial immunity to the genital tracts of naive animals. The lymphokine profiles in the culture supernatants of proliferating Chlamydia-specific CD4+ T cells obtained from mice following resolution of a primary infection and after secondary challenge were assayed by an enzyme-linked immunoadsorbent assay. Protective CD4+ T cells restimulated in vitro secreted interleukin 2, gamma interferon, and interleukin 6, lymphokine profiles characteristic of both Th1- and Th2-like responses. Resting CD4+ T cells obtained from mice 4 months following resolution of a primary infection were also capable of conferring significant levels of adoptive protective immunity to naive mice. These findings support an important role for CD4+ T cells in acquired immunity to chlamydial infection of the genital tract and indicate that protective CD4+ immune responses in this model are relatively long lived.     

淋巴瘤样丘疹病临床病理分析

目的 探讨淋巴瘤样丘疹病(LyP)的临床病理特征、免疫表型及预后.方法 分析13例LyP的临床病理资料,用LSAB法、EliVision法行T淋巴细胞、B淋巴细胞、活化淋巴细胞和细胞毒性等12种免疫组织化学标记,原位杂交检测EB病毒.结果 13例LyP中男6例,女7例,平均年龄26.4岁,皮损多表现为四肢、躯干无症状的多发性丘疹、结节.组织学分型:A型6例,B型1例,c型6例,主要在真皮与皮下脂肪组织内浸润,主要浸润方式分别为楔形、带状及片状、结节状.13例中8例有瘤细胞亲表皮现象;1例B型无大瘤细胞,余12例的大瘤细胞均表达CD30.13例瘤细胞均表达2～3个T细胞标记(CD3、CD5或CD45RO)及1～3个细胞毒性标记[T细胞胞质内抗原(TIA)-1、粒酶B或穿孔素];13例均表达CD4、4例表达CD8、1例表达CD15、1例表达CD20(局灶阳性),均不表达间变性淋巴瘤激酶(ALK)-1.亲表皮之瘤细胞多为CD3~+、CD4~+、CD8~-表型.13例中1例EBER1/2原位杂交阳性.获随访的12例均存活.结论 LyP有独特的临床病理表现和免疫表型,预后较好.A型和C型中亲表皮的瘤细胞均为核扭曲、深染,似覃样霉菌病细胞,推测其与CD30~+大瘤细胞可能来源于不同的克隆群体有关.EB病毒与LyP可能无明确的相关性.     

Alveolar soft part sarcoma of the uterine cervix

We describe two cases of alveolar soft part sarcoma (ASPS) that occurred as a primary lesion in the uterine cervix. In both cases, the tumor exhibited the typical histologic features of ASPS. In one case, the material for immunohistochemical staining and electron microscopy was available, and the findings of these studies were consistent with the diagnosis of ASPS. A review of the literature disclosed seven previous cases of ASPS occurring in the female genital tract. The tumor was located in the uterine cervix in only three cases. Although ASPS most commonly involves the soft tissues of the extremities and the head and neck region, it can also occur in rather unusual locations such as the female genital tract. Pathologists should be aware of these unexpected occurrences.     

Resolution of secondary Chlamydia trachomatis genital tract infection in immune mice with depletion of both CD4+ and CD8+ T cells

The essential role of T cells in the resolution of primary murine Chlamydia trachomatis genital tract infection is inarguable; however, much less is known about the mechanisms that confer resistance to reinfection. We previously established that CD4+ T cells and B cells contribute importantly to resistance to reinfection. In our current studies, we demonstrate that immune mice concurrently depleted of both CD4+ T cells and CD8+ T cells resisted reinfection as well as immunocompetent wild-type mice. The in vivo depletion of CD4+ and CD8+ T cells resulted in diminished chlamydia-specific delayed-type hypersensitivity responses, but antichlamydial antibody responses were unaffected. Our data indicate that immunity to chlamydial genital tract reinfection does not rely solely upon immune CD4+ or CD8+ T cells and further substantiate a predominant role for additional effector immune responses, such as B cells, in resistance to chlamydial genital tract reinfection.