Lymphomas of the female genital tract: a study of 186 cases and review of the literature

Malignant lymphomas in the female genital tract are rare, and those arising from this tissue system are extremely uncommon. Most pertinent reports lack clear references to the accepted classifications or failed to apply immunomarkers and molecular techniques for a reliable diagnosis. We analyzed a large group of patients with primary and secondary lymphomas of the female genital tract classified on the basis of the recent WHO consensus. A total of 186 patients with malignant lymphoma detected in the female genital tract were selected from the files of the Kiel Lymphoma Registry covering the period of 1974 to 2004. Stringent criteria were applied to separate systemic versus secondary lymphomas. All cases were reviewed on the basis of conventionally stained sections, relevant immunohistochemistry using the alkaline phosphatase/anti-alkaline phosphatase technique, and clinical information, as far as available. When required, gene rearrangement analysis was performed, including TCR-gamma chain gene and the three FR fragments of the IgG heavy chain gene. In addition, typical chromosomal translocations were detected by means of the FISH technique to verify the diagnosis, where needed. Thirty-seven percent of the cases were systemic lymphomas and 63% were mostly extranodal lymphomas primary to the female genital tract. The adnexa were involved in 87 cases, followed by uterine corpus in 23 cases, uterine cervix in 17 cases, portio in 9 cases, vagina in 11 cases, and vulva including clitoris in 8 cases. In 31 cases, two or more adjacent sites were involved. In both (primary and secondary) groups, the adnexa were the prevailing site of involvement. As expected, the overwhelming majority of cases were of B phenotype. The most frequent type of lymphoma proved to be diffuse large B-cell lymphoma, closely followed by follicular lymphoma, including all 3 grades of malignancy. Burkitt lymphoma showed a rather similar frequency. Marginal zone lymphoma occurred exclusively as primary lesions in the uterine mucosa. Lymphoplasmacytic lymphoma was restricted to the vulvo-vaginal area and occurred in women over 60 years of age. In conclusion, our study provides a thorough overview of various types of lymphoma affecting the female genital tract primarily or secondarily, which were classified on the basis of a widely accepted WHO classification. Although quite rare, our report should remind the pathologist of considering malignant lymphomas while reading biopsies taken from female genital organ.     

Malignant melanoma involving the ovary: a clinicopathologic and immunohistochemical study of 23 cases

Ovarian malignant melanoma (MM), primary or metastatic, is an extremely rare tumor and in the absence of a previous diagnosis can represent a diagnostic challenge. We present the clinicopathologic and immunohistochemical features of 23 cases seen in our institution over a period of 40 years (1962-2001). The patients' age ranged from 14 to 53 years (mean 35.7 years). Ethnicity was known in 19 patients: 14 white, 4 Hispanic, and 1 black. A previous history of MM was definitively obtained in 14 patients; in these cases, the interval between the primary MM and the ovarian metastasis ranged from 15 to 228 months (mean 77.7 months). The tumor was unilateral in 19 and bilateral in 4 cases. The tumor size ranged from 4.5 to 23 cm (average 10 cm); the melanoma arising in a cystic teratoma was 0.2 mm in thickness. The tumor was grossly pigmented in 8 cases (35%). The architectural pattern was nodular (8 cases), diffuse (6 cases), nodular and diffuse (5 cases), nested (3 cases), and lentiginous arising in a teratoma (1 case). Follicle-like spaces were seen in 8 cases, pseudo-glandular areas in 1 case, pseudo-myxoid areas in 1 case, and cords in 1 case. The tumor cell type was epithelioid in 19 cases, spindled in 2 cases, mixed epithelioid and spindled in 1 case, and small cell in 1 case. Nucleoli were prominent in 18 cases, and nuclear inclusions were present but rare in the majority of cases. Nuclear grooves were seen in 3 cases. Necrosis was extensive in 8 cases, focal in 10 cases, and was absent in 5 cases. In 8 cases, initial diagnoses included sex cord stromal tumor, germ cell tumor, sarcoma, or undifferentiated carcinoma. S-100 was positive in 18 of 19 cases, HMB-45 in 17 of 20 cases, MART-1 in 13 of 15 cases, tyrosinase in 10 of 15 cases, and Mitf in 8 of 14 cases. Inhibin was positive in 3 of 14 cases. Calretinin was focally positive in 1 of 12 cases. Treatment performed in 18 of the cases are as follows: oophorectomy with/without chemotherapy (10); total abdominal hysterectomy with bilateral salpingo-oophorectomy with/without chemotherapy (6); vaginal hysterectomy, bilateral salpingo-oophorectomy, and chemotherapy (1); and total abdominal hysterectomy with salpingo-oophorectomy (1). Follow-up ranging from 2 to 96 months was available in 18 patients. All but one had metastases in other organs, most often in the lungs. Thirteen patients died of disease (range 2-76 months), 3 are alive with disease (6-18 months), and 2 have no evidence of disease at 24 and 96 months; one was the patient with melanoma arising within a teratoma. In conclusion, MM involving the ovary is a rare disease, predominantly seen in women of reproductive age, and is associated with a poor prognosis. The tumor is most often metastatic from another site and is unilateral in most cases. Nodular or diffuse pattern and epithelioid cell type are most frequently seen, and the tumor can be mistaken for germ cell and sex cord stromal tumors. S-100 is the most sensitive marker. MART-1 was positive in the few cases that were negative with HMB-45. Inhibin can be focally positive in some cases.     

Urothelial carcinoma involving the gynecologic tract: a morphologic and immunohistochemical study of 6 cases

Spread of urothelial carcinoma (UC) to the female genital tract occurs in a small subset of women with UC. We studied 6 patients with involvement of various gynecologic (GYN) sites and detailed natural history and pathologic features. Four patients initially presented with bladder lesions, including 1 high-grade pTa tumor, 2 pT1 tumors, and 1 pT2 tumor; 1 patient presented with pT2 disease of the renal pelvis and 1 with GYN involvement in the form of vulvar Paget's disease. For the 5 patients presenting with UC, time to GYN involvement was 2 to 8 years; vaginal bleeding (n=4) was the main presenting symptom, and the first site of involvement was the vagina (n=4) or cervix (n=1). GYN sites displayed an array of morphologies and growth patterns that may be seen in both UC and GYN primary tumors. The presence or absence of invasion in the original UC did not dictate whether GYN sites would exhibit invasive disease or whether disease would present as continuous or "skip" lesions. Immunohistochemistry for at least 1 GYN site per patient revealed diffuse, strong CK7 and focal to diffuse strong CK20 positivity in all cases, as well as at least focal p16 positivity in 5 of 6 cases. HPV in situ hybridization was negative in all cases. At last follow-up, 3 patients had died from UC and 3 were alive with recurrent disease/documented metastasis. Our findings highlight the morphologic and immunohistochemical overlap between primary GYN squamous lesions and GYN involvement by UC and hence the importance of clinical history in ensuring an accurate diagnosis.     

Transitional cell carcinoma involving the prostate: a clinicopathological retrospective study of 76 cases

PURPOSE: We reviewed the degree to which extension from transitional cell carcinoma into the prostate affects survival. We also compared whether prostatic stromal invasion occurring via direct extension through the bladder wall differs from stromal invasion arising intraurethrally. MATERIALS AND METHODS: A total of 76 men who underwent radical cystectomy for transitional cell carcinoma also had prostate involvement. Patients were separated into group 1-18 with primary bladder tumor extending transmurally through the bladder wall to invade the prostate and group 2-58 with prostate involvement arising from within the prostatic urethra. In the latter group the degree of prostate invasion was classified as urethral mucosal involvement, ductal/acinar involvement and stromal invasion. RESULTS: The 5-year overall survival and recurrence-free rate were 22% and 28% in group 1 versus 43% and 45% in group 2, respectively. In group 2 survival rates were similar in those with prostatic urethral and ductal tumors (without stromal invasion). Five-year overall survival rates without and with stromal invasion were 49% and 25%, respectively (p = 0.024). Prostate involvement decreased survival, which varied according to primary bladder stages (Pis, P1, P2a/b and P3a/b, p = 0.004) or superficial (Pis, Pa and P1) and muscle invasive (P2a/b and P3/b, p = 0.045), disease in 2 groups. Those with positive lymph nodes experienced poorer outcomes in each group. The 5-year overall survival rate in the 19 men with positive lymph nodes was 13% and it was 44% with negative lymph nodes (p = 0.034). The major prognostic factors were age, degree of prostate invasion and lymph node involvement. CONCLUSIONS: The invasion pathways of prostate invasion in patients with transitional cell bladder carcinoma have a statistically significant prognostic role in survival. Transitional cell carcinoma of the bladder extending into the prostate through the bladder wall and bladder carcinoma that did not directly infiltrate the prostate through the bladder wall are 2 distinct clinicopathological entities that should not be included in the same staging grade.     

Phyllodes tumors of the breast: a case series of 106 patients

BACKGROUND: Phyllodes tumors (PTs) of the breast are rare, and their prognosis and treatment are still subject of discussion. The purpose of this study is to clarify therapeutic aspects and prognostic factors of this disease. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 106 patients who had histologically confirmed PTs collected over a period of 10 years. RESULTS: The mean age was 39.5 years (14-71 years). The mean tumoral size was 83 mm (15-250). According to criteria of Azzopardi and Salvadori, tumors were classified into 3 groups: benign (62 cases, 58.4%), borderline (16 cases, 15%), and malignant (28 cases, 26.4%). Eighty-two patients (77.4%) were treated conservatively (62 benign, 11 borderline, and 9 malignant) and 24 (22.6%) by radical surgery (5 borderline and 19 malignant). For malignant PTs treated by enucleation or local excision with or without reexcision of the tumor bed, the 5-year overall and disease-free survivals were 28.5% and 15.6% versus 72.7% and 73.6% when the surgery was radical (mastectomy with or without axillary dissection) (P = .12 and P = .0022). For the other histotypes, this difference disappeared. The rate of recurrence was 12.2% (13) after a mean follow-up of 39 months (5 benign, 2 borderline, and 5 malignant). The treatment of recurrences consisted of radical mastectomy (8 cases), simple mastectomy (2 cases), and local excision in 3 cases. Eight patients developed metastases, 2 of whom after recurrences. The 5-year overall and disease-free survivals were 86.54% and 78%, respectively. In univariate analysis, age and recurrences are not of prognostic value for survival, whereas tumor size, histotype, necrosis, cytonuclear atypia, tumor margins, and number of mitosis were significant prognostic factors for survival. In a multivariate study, only cytonuclear atypia remained an independent predictor for survival. CONCLUSION: According to our results, we recommend for malignant PT a simple mastectomy, whereas for borderline and benign PT, treatment is based rather on wide excision passing in healthy tissue.     

HAROW: the first comprehensive prospective observational study comparing treatment options in localized prostate cancer

Purpose

To collect data on primary treatment decision and follow-up in patients with diagnosed, histologically confirmed localized (T1a–T2c/N0/M0) prostate cancer (PCa) for up to 5 years in a prospective observational non-interventional study.

Methods

Patients were non-randomly allocated to one of the five treatment strategies: hormone therapy, active surveillance, radiation, operation, or watchful waiting.

Results

A total of 3169 patients were included by 259 participating sites; 2957 patients had at least one follow-up visit. 54.8 % of tumors at baseline were staged as T1c, 38 % as T2a–T2c, and 7.1 % as T1a or T1b (missing: 0.2 %). 38.9, 32.6 and 26.6 % of patients were classified as low risk, intermediate risk, and high risk according to d’Amico, respectively (missing: 1.8 %). 56.6 % of patients underwent prostatectomy as primary therapy, 16.4 % received radiation, 6.9 % HT, 15.8 and 4.3 % decided for AS or WW. Mean follow-up was 28.4 months. Progression rates were between 8.6 % (RT) and 33.1 % (AS).

Conclusion

Whereas RP remains the main treatment option of localized PCa, active surveillance appears to become an accepted and selectively employed treatment option. Careful selection of patients is documented by the highest proportion of patients with low risk (82.5 %), PSA density <0.2 ng/ml/ml (77.5 %), T1 staging (83.6 %), Gleason score ≤6 (92.5 %), ≤2 positive biopsies (79.4 %), and lowest mean PSA (5.8 ng/ml) in the AS group. The relatively high progression rate in the AS group has to be considered in the context of treatment changes; 71/155 patients had a documented change of treatment and 62 of them with a follow-up period of >3 months.

     

Macroporous calcium phosphate ceramic: a prospective study of 106 cases in lumbar spinal fusion

Macroporous biphasic calcium phosphate (MBCP, Triosite) is well known for its safety, absence of allergenicity, and excellent bone-bonding capacity, and it has been widely used as a bone graft substitute in orthopaedic, ENT, and dental surgery. This study investigates the clinical performance of this synthetic porous ceramic in a series of 106 patients, mainly with degenerative spine aetiologies (95/106) and with a minimum follow-up of 2 years. All patients were treated with posterior correction involving the semi-rigid New Orleans instrumentation. Spinal fusion was always performed using MBCP granules mixed with autogenous bone chips and bone marrow obtained from the local spine. Fusion of the spine was confirmed for 100 patients, and 6 non-unions were observed (3 resulting from primary spondylolisthesis). This study shows that MBCP provides suitable results in spinal fusion involving a semi-rigid instrumentation. Because the indication of degenerative spine is not very favorable to fusion, this technique appears to be a good alternative to autografts and could decrease patient morbidity resulting from iliac bone grafting.     

Endometrioid carcinoma simultaneously involving the uterus and the fallopian tube: a clinicopathologic study of 13 cases

Although the simultaneous presentation of endometrial and ovarian carcinomas of the endometrioid type is well described, little is known about a similar phenomenon involving the endometrium and fallopian tube (FT). We present the clinicopathologic features of 13 such cases seen in the Department of Pathology at The University of Texas M.D. Anderson Cancer Center over an 8 year period (1995 to 2002). FT tumors that could have represented luminal extension of the endometrial carcinoma or that represented an unequivocal metastasis to the FT were excluded. The patients' ages ranged from 34 to 77 years (median 54). The most common symptom was abnormal uterine/vaginal bleeding (11) and all of the patients were considered overweight or obese (mean body mass index was 41). The size of the endometrial carcinomas ranged from 0.3 to 8 cm. According to the FIGO grading of the endometrial endometrioid carcinomas, the cases were distributed as follows: Grade 1 (3) and Grade 2 (10). In 2 cases, there were also small areas of other histologic types, papillary serous carcinoma (1 case), and papillary endometrial carcinoma of intermediate grade (another case). The size of the fallopian tube carcinomas ranged from 0.2 to 17.5 cm. Seven of these tumors were located in the distal/fimbriated end of the FT. There was bilateral involvement in 2 cases. Three of the FT tumors were in situ. The grades of the fallopian tube carcinomas were as follows: Grade 1 (2), Grade 2 (6), and Grade 3 (2). In situ components were seen in all cases. One fallopian tube carcinoma was mixed with serous carcinoma. In 4 cases, there was also an endometrioid carcinoma involving the ovary, all of them with an intact ovarian capsule. Patients were treated as follows: total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH/BSO) (4), TAH/BSO/chemotherapy (chemo) (4), TAH/BSO/radiation (3), and TAH/BSO/chemo/radiation (2). Follow-up ranging from 6 to 54 months was available in 10 patients: 1 patient died of disease (at 38 mo), 1 patient is alive with disease (at 9 mo), 7 patients have no evidence of disease (6 to 54 mo), and 1 patient died of metastatic endometrial carcinoma (at 9 mo). Simultaneous endometrioid carcinomas of the uterus and FT are unusual and occur primarily in obese perimenopausal women. The tumors are predominantly well or moderately differentiated with dissimilar endometrial and FT grades. The FT carcinoma is usually unilateral and located at the distal end of the tube.     

Malignant tumors of the anus. A study of 106 cases

This study of 106 cases of malignant tumors of the anus has shown that the diagnosis was often made late. In 15 percent of the patients the tumor was at the anal margin; in 61 percent, in the anal canal, and in 24 percent, the tumor was so extensive that its origin could not be determined clinically. In nearly half of the cases, the cancers were advanced and showed perirectal metastases. Surgical treatment was the rule, with local excision for carcinomas of the anal margin and abdominoperineal resection for tumors of the canal. The general prognosis over a period of several decades remains poor. We found a 20 percent 5 year survival rate for epidermoid carcinoma of the anal canal, excluding deaths from causes other than cancer during the follow-up period.     

腹膜后局限性Castleman病20例临床诊治及预后分析

目的 探讨腹膜后局限性Castleman病的临床特征、诊治策略及影响预后的因素,提高伴副肿瘤性天疱疮(PNP)的Castleman病的诊治水平.方法 回顾性分析1993年1月至2009年5月在北京大学第一医院普通外科接受手术治疗的20例腹膜后Castleman病患者的临床资料,并将13例腹膜后Castleman病伴PNP患者的临床资料与同期7例单纯腹膜后Castleman病患者进行比较,分析两者在发病特点、部位、实验室检查、手术策略、病理特征及外科治疗效果的不同.结果 (1)本组腹膜后Castleman病多见于中青年(中位年龄36岁),发病部位多位于肾旁(14/20,70%)及髂窝(4/20,20%),左侧腹膜后多见,病理分型以透明血管型为主,腹膜后Castleman病合并PNP组的性别、年龄、肿瘤发病部位、大小及病理分型与单纯腹膜后Castleman病组无明显区别(P>0.05);(2)本组腹膜后Castleman病合并PNP患者较易合并闭塞性细支气管炎(8/13),有血清肿瘤标志物癌胚抗原或CA242升高现象(3/8);(3)本组腹膜后Castleman病常有包膜,与邻近脏器边界清晰,手术较为容易,但合并PNP的腹膜后Castleman病的生物学行为有恶性倾向及伴发子灶特征,有侵及邻近血管及术后局部复发可能;(4)Kaplan-Meier及Log-Rank生存分析显示,腹膜后Castleman病合并PNP患者5年生存率为42.8%,平均生存时间30个月,明显低于单纯腹膜后Castleman病组(P<0.05),是否合并闭塞性细支气管炎以及肿瘤能否根治切除是影响腹膜后Castleman病患者预后的重要因素.结论 腹膜后Castleman病伴PNP具有独特的临床特征,早期诊断和切除肿瘤、及时终止致病抗体的产生,是成功治愈的关键.     

Technique of photodynamic therapy for disseminated intraperitoneal malignant neoplasms. Phase I study

Patients with disseminated intraperitoneal malignant neoplasms were given intra-abdominal photodynamic therapy. Patients received dihematoporphyrin ethers intravenously 48 to 72 hours before laparotomy at doses of 1.5 to 3.0 mg/kg. At operation, as much tumor as possible was resected. Red light (630 nm) was delivered to all peritoneal surfaces from an argon-pumped dye laser at doses ranging from 0.2 to 3.0 J/cm2 in an escalating fashion. Viscera and peritoneal surfaces were anatomically isolated and exposed to light for intervals calculated to deliver the prescribed energy. Light was delivered to mesentery and bowel by a flat-cut optical fiber, while other areas, including diaphragm, viscera, omental bursa, gutters, and pelvis, were delivered light through a diffusing wand. Twenty-three patients (13 with ovarian cancer, eight with sarcoma, and two with pseudomyxoma peritoneii) underwent photodynamic therapy. Five of eight patients cleared positive peritoneal cytologies after treatment. Six patients remained clinically free of disease for up to 18 months, and five patients had treatment-related complications. Intraperitoneal phototherapy is technically feasible and deserving of clinical evaluation.     

乳腺小管癌的临床病理分析

目的 探讨乳腺小管癌的临床病理特征、诊断与鉴别诊断要点。方法 通过光镜和免疫组化方法对4例乳腺小管癌进行临床病理分析,结合文献对其临床表现、病理形态特点及鉴别诊断进行探讨。结果 4例乳腺小管癌仅3例有可触及的肿物,另1例仅在B超下发现两个低回声肿块。镜下4例均由高分化的小管结构组成,存在开放的管腔,被覆单层上皮细胞,腺管形状不规则成角状,内含嗜碱性分泌物,可见顶浆分泌的小突起,未见肌上皮细胞及完整的基底膜成分,SMA（-）。间质增生并富于细胞。3例伴有导管内癌,其中1例伴有平坦上皮不典型增生。结论 小管癌的正确诊断需组织形态和免疫组化相结合,并与硬化性腺病、微小腺体腺病、复杂硬化性腺病/放射状瘢痕、以腺管结构为主的乳腺浸润性导管癌等病变相鉴别。     

Male breast cancer: a clinicopathologic study of 97 cases.

From 1949 through 1976, 97 men have been treated at Memorial Hospital for primary operable breast cancer. Seven per cent had intraductal carcinoma. Of the patients with invasive carcinoma 30% were pathologic stage I, 54% stage II, and 16% stage III. Fourty-six per cent had pathologically negative axillary lymph nodes. The most common type of tumor was infiltrating duct carcinoma. Fourty per cent of the patients had microscopic gynecomastia. None of the eight patients with intraductal or intracystic carcinoma died of cancer. Survival of the entire group of men with invasive carcinoma was 40% after ten years. The ten year survival for men with negative nodes was 79%, for men with positive nodes 11%. Comparison with a series of 304 women with breast cancer operated on at Memorial Hospital in 1960 revealed no difference with regard to incidence of positive axillary lymph nodes or stage of disease. There was, however, a significantly lower survival rate for men. This poorer prognosis was limited to those men with pathologically positive axillary nodes.