Transmission Electron Microscopy: A Surgical Pathology Tool for Neuroblastoma.

Pediatric small round blue cell tumors (PSRBCT) are an intriguing and challenging collection of neoplasms. Light microscopy of small round blue cell tumors identifies small round cells. They harbor a generally hyperchromatic nucleus and relatively scanty basophilic cytoplasm. Pediatric small round blue cell tumors include several entities. Usually, they incorporate Wilms tumor, neuroblastoma, rhabdomyosarcoma, Ewing sarcoma, retinoblastoma, lymphoma, and small cell osteosarcoma, among others. Even using immunohistochemistry, the differential diagnosis of these neoplasms may be controversial at light microscopy. A faint staining or an ambiguous background can deter pathologists from making the proper diagnostic decision. In addition, molecular biology may provide an overwhelming amount of data challenging to distinguish them, and some translocations may be seen in more than one category. Thus, transmission electron microscopy (TEM) can be extremely valuable. Here we emphasize the modern protocol for TEM data of the neuroblastoma. Tumor cells with tangles of cytoplasmic processes containing neurosecretory granules can diagnose neuroblastoma.

Histologic classification of prostate cancer.

Apart from the typical acinar morphology observed in more than 90% of prostatic adenocarcinomas, a spectrum of morphological variants and prostate cancer subtypes exists. Two nosologically different groups can be distinguished: the variants of conventional acinar cancer and cancers with histological pattern, which are unusual for the prostate. Variants of conventional prostate cancer (pseudohyperplastic, foamy gland, hypernephroid, atrophic, microcystic, with Paneth cell-like changes, with collagenous micronodules, with glomeruloid formations, oncocytic) do not have any known prognostic significance and are graded according to the Gleason system. Unusual cancer types (ductal carcinoma, mucinous [colloid] carcinoma, mucinous signet ring cell carcinoma, small cell carcinoma, sarcomatoid carcinoma and carcinosarcoma, pleomorphic giant cell carcinoma, squamous and adenosquamous carcinoma, basal cell and adenoid cystic carcinoma, lymphoepithelioma-like carcinoma, primary urothelial carcinoma of the prostate) have mostly a very poor prognosis and are therefore real nosological entities.

Update on the pathology of testicular tumors.

At least 90% of testicular tumors belong to the group of germ cell tumors (GCTs), which are classified according to the 2004 World Health Organization (WHO) classification. Race is one of the most important etiologic factors in the development of GCTs. White men living in Western industrialized countries show the highest rates of incidence. Known risk factors are cryptorchidism, contralateral GCT, familial association, infertility, testicular atrophy, trauma, surgery, socioeconomic status, environmental factors, and occupational exposure to noxious conditions. For the most part, the morphology of GCTs is well known to pathologists. There are, however, some little-known rare entities like anaplastic type of spermatocytic seminoma. In the group of nonseminomatous GCTs are emerging the somatic-type malignancies (carcinomas, sarcomas) arising in teratomas. Tumors of sex cord/gonadal stroma account for 1.6-6% of adult testicular tumors and are somewhat more frequent in children. Absolutely nothing is known about the epidemiology, histogenesis, and possible etiology of these tumors, which derive from Leydig, Sertoli, granulosa, and theca cells. In the group of "miscellaneous tumors," lymphomas are the most frequent testicular tumors in men older than age 50.

Handling and reporting of orchidectomy specimens with testicular cancer: areas of consensus and variation among 25 experts and 225 European pathologists.

AIMS: The handling and reporting of testicular tumours is difficult due to their rarity. METHODS AND RESULTS: A survey developed by the European Network of Uro-Pathology (ENUP) and sent to its members and experts to assess the evaluation of testicular germ cell tumours. Twenty-five experts and 225 ENUP members replied. Areas of disagreement included immaturity in teratomas, reported by 32% of experts but 68% of ENUP. Although the presence of rete testis invasion was reported widely, the distinction between pagetoid and stromal invasion was made by 96% of experts but only 63% of ENUP. Immunohistochemistry was used in more than 50% of cases by 68% of ENUP and 12% of experts. Staging revealed the greatest areas of disagreement. Invasion of the tunica vaginalis without vascular invasion was interpreted as T1 by 52% of experts and 67% of ENUP, but T2 by the remainder. Tumour invading the hilar adipose tissue adjacent to the epididymis without vascular invasion was interpreted as T1: 40% of experts, 43% of ENUP; T2: 36% of experts, 30% of ENUP; and T3: 24% of experts, 27% of ENUP. CONCLUSIONS: There is remarkable consensus in many areas of testicular pathology. Significant areas of disagreement included staging and reporting of histological types, both of which have the potential to impact on therapy.

Therapy-resistant metastasizing anaplastic spermatocytic seminoma: a cytogenetic hybrid: a case report.

BACKGROUND: Anaplastic spermatocytic seminoma is a rare variant of the conventional spermatocytic seminoma, with only 6 cases reported up to now. The anaplastic variant contains only the medium-sized cell type, hallmarked by large-sized nucleoli, whereas the small lymphocyte-like and giant cells typical of the conventional spermatocytic seminoma are lacking. CASE: We report herein an unusual case of a 40-year-old man with an anaplastic spermatocytic seminoma which metastasized first to the retroperitoneal lymph nodes and, something never before reported, subsequently to the lung and other organs. The immunophenotype with c-kit and SALL4 positive and PLAP, as well OCT 3/4 negative tumor cells were identical to those of conventional spermatocytic seminoma. Cytogenetically the tumor cells showed a gain of chromosome 9, typical for spermatocytic seminoma, but simultaneously also the short arm 12p were overexpressed--an overexpression crucial to the aggressive behavior of seminomas and other nonseminomatous tumors but never before encountered in spermatocytic seminoma. CONCLUSION: The current opinion is that seminoma and nonseminomatous germ cell tumors develop from a common primitive progenitor cell, whereas spermatocytic seminomas develop from differentiated spermatogonia. The herein presented cytogenetic hybrid tumor shows that a crossover between the two different histogenetic "tracks" is possible.

Traumatic neuroma of the anus after Milligan-Morgan hemorrhoidectomy.

There are several clinical settings of traumatic neuroma and a few may occur following surgical procedures. A 42-year-old man presented with anal pain five years after a Milligan Morgan hemorrhoidectomy for prolapsing hemorrhoids. A 4×4×3 mm sized anal polyp was seen during a rectal examination at a follow-up five years after surgery. The patient complained of point tenderness, pruritus, and anal discomfort as well as fecal retention. An endoscopy revealed a rectal polyp. Remarkably, histopathological examination and immunohistochemistry of the excised polyp showed a polypoid traumatic neuroma of the rectal plexus. After the excision of the polyp, the patient's complaint resolved completely. Traumatic neuromas may be a cause of significant pain and tenderness in patients with anal surgery or repair of anal lacerations. Interestingly, this is the second case of anal traumatic neuroma since Dr. Marks' first case in 1956 and is a possible complication of Milligan Morgan hemorrhoidectomy for prolapsing hemorrhoids. Similar complications of rectal surgery are reviewed.

Adult type granulosa cell tumor of the testis with a heterologous sarcomatous component: case report and review of the literature.

Adult testicular granulosa cell tumors are rare sex cord- stromal tumors of which only 45 have been previously reported. As compared with their ovarian counterparts, these tumors may follow a more aggressive course because the proportion of malignant cases is higher. We report here a unique case of a 78-year Caucasian with a left sided adult type granulosa cell tumor with a heterologous sarcomatous tumor component. A heterologous sarcomatous component has occasionally been observed in ovarian tumors but never in testicular granulosa cell tumors. The sarcomatous component showed a higher number of mitotic figures (1/Hpf) and a marked proliferation rate (up to 50% Ki 67 positive cells) compared with the granulosa type tumor component. CD 99 and the progesterone receptor were positive in both tumor components, inhibin and calretinin only in the granulosa cells, and pancytokeratin only in the sarcomatouse one. Key words: testis - ovary - granulosa cells - sarcoma - inhibin Runing title: testicular sarcomatous granulosa tumor. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6959043481207016.

Interactions of human peritoneal mesothelial cells with serous ovarian cancer cell spheroids--evidence for a mechanical and paracrine barrier function of the peritoneal mesothelium.

BACKGROUND: Ovarian carcinoma spreads by implantation of tumor cells onto the peritoneal mesothelium. We established a 3-dimensional coculture model to simulate the interactions of ovarian carcinoma cell aggregates with human peritoneal mesothelial cells (HPMC). METHODS: Multicellular tumor spheroids (MCTS) of the human ovarian cancer cell line SK-OV-3 were directly inoculated onto either confluent HPMC monolayers or their submesothelial matrix or were cocultured with mesothelium without direct cellular contact. RESULTS AND DISCUSSIONS: Inoculation of MCTS onto submesothelial matrix resulted in rapid attachment (within 30 minutes) of the tumor cell aggregates followed by rapid dissemination (within 12 hours) and growth of tumor cells. Intact mesothelium increased the time required for MCTS attachment (up to 180 minutes) and led to almost complete inhibition of tumor cell dissemination and to 47% tumor growth suppression. Bromodeoxyuridine incorporation into tumor cell nuclei was almost completely abolished in cocultured MCTS. Growth also was inhibited in MCTS treated with supernatants of HPMC. Analysis of coculture supernatants revealed that HPMC-derived transforming growth factor ß (TGF-ß) was almost completely bound by MCTS. Addition of a function-blocking anti-TGF-ß antibody (30 µg/mL) to the cocultures abrogated the growth inhibitory effect of the mesothelium by 50%. CONCLUSIONS: The present model provides a dynamic system to study the complex interactions of ovarian carcinoma cells with HPMC over extended periods and suggests that the mesothelium constitutes a mechanical and partly TGF-ß-mediated paracrine barrier to the progression of ovarian cancer.

Thyroid-like follicular carcinoma of the kidney in a patient with nephrolithiasis and polycystic kidney disease: a case report.

Thyroid-like follicular carcinoma of the kidney (TLFC), a rare neoplasm with low malignant potential, is histologically similar to primary thyroid follicular carcinoma, but characteristically lacks thyroid immunohistochemical markers. We report a case of 34-year old patient with nephrolithiasis. Ultrasound revealed hepatorenal cysts consistent with adult type polycystic kidney disease (ATPKD) and a cytologically confirmed left kidney tumor. Nephrectomy specimen contained sharply demarcated lesion of unusual morphology. Tubular and cystic structures lined by mostly cuboidal cells and filled with amorphous eosinophillic material, reminiscent of follicular carcinoma of the thyroid gland, were diagnostic for TLFC. Thyroid markers were negative. To our knowledge this is the first report of TFLC associated to ATPKD. Brief review of previously published TFLCs, possible relationship between entities and differential diagnosis are discussed. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8067946569612694.

Rare tumors of the testis and mesothelial proliferation in the tunica vaginalis.

An increasing number of rare testicular tumors have been recognized in the recent years with a wide and heterogeneous spectrum of morphologies. The utility of ancillary studies, including immunohistochemistry, is often limited and is important for the pathologists to be aware of these entities, because they require a comprehensive pathological and clinical approach for an appropriate treatment.

Teratoma with somatic-type malignant components of the testis. A review and an update.

Malignant transformation of germ cell tumors into somatic malignancy is uncommon. Its presentation differs from series to series, with 43 % of adult cases identified within the primary tumors and the remainder at the time of relapse or in the metastasis. Patients with stage I disease enjoy an excellent prognosis; whereas in metastatic sites when not completely resectable, the somatic type malignancies suffer a dismal prognosis. Radical surgery is significant for the prospects of cure and is standard chemotherapy for germ cell tumors; a transformation-oriented treatment can be effective for these patients. A deeper understanding of the biology of this phenomenon is essential for clinicians involved in such malignancies in order to permit a better control of the disease.

The challenging diagnosis of the rhabdoid carcinoma of the pelvis: a case report with literature review.

Rhabdoid tumor is an uncommon neoplasia characterized by a monotonous population of large, noncohesive cells with vesicular nuclei and large nucleoli. The misleading name was originally suggested because of the striking morphologic resemblance to other skeletal muscle tumors, but neither ultrastructural nor immunohistochemical features support a myogenic origin for this tumor. The rhabdoid tumors of the kidney in pediatric age are characterized by mutation or deletion of 22q11. In adults, tumors with rhabdoid features are uncommon neoplasia reported in different anatomic sites, but their histogenesis is still unclear. We focused on the literature data regarding the rhabdoid features in pelvic and renal tumors, and we describe a carcinoma involving the pelvis and the kidney with exclusive rhabdoid features, which make the anatomical allocation of the tumor difficult. The tumor did not exhibit any similarities to conventional histologic types of renal cell cancer, not even of the sarcomatous type. Tumor cells showed a strong positivity for epithelial markers (AE1/AE3 and CK 8) and for vimentin, whereas they were negative for skeletal and smooth muscle markers. The nuclei of the tumor cells demonstrated a INI1-positive immunohistochemical stain, indicating the lack of mutation or deletion of the 22q11 chromosome. The appropriate diagnosis is that of an extrarenal high-grade rhabdoid carcinoma originating from the urothelium of the renal pelvis. The decision as to whether the tumor arose primarily in the renal parenchyma or in the renal pelvis could be of therapeutic importance. Appropriate immunohistochemical markers can help in the difficult differential diagnosis.

Polypoid intestinal metaplasia of the external urethral meatus.

A 33-year-old male patient presented with a 1.5-cm polypoid lesion at the edge of the urethral meatus that showed a gross appearance similar to that of a urethral caruncle in the female. The histological features revealed a superficially ulcerated lesion composed of colonic-type mucosal glands with focal regenerative atypia. This case appears to be the first reported one on an intestinal-type polyp in this site. The patient had no further problems after excisional biopsy.

Early viral load and recipient interleukin-28B rs12979860 genotype are predictors of the progression of hepatitis C after liver transplantation.

There have been few detailed studies of viral kinetics after liver transplantation (LT), and conflicting data have been reported on viral loads and the severity of recurrent hepatitis C virus (HCV) disease. This long-term study aimed to examine (1) the impact of HCV RNA levels at specific points in time within the first year and (2) the influence of interleukin-28B (IL-28B) genotypes on patient outcomes and the severity of recurrent HCV disease. The viral loads were measured 2, 4, 12, 24, and 48 weeks after LT, and the recipient/donor IL-28B genotypes of 164 patients were determined. A Cox regression analysis showed that the viral load at week 2 was an independent negative predictor of recipient outcomes. A week 2 viral load ≥ 6.0 log(10) IU/mL was significantly associated with reduced patient survival. After a mean follow-up of 6.5 years, 21 of 164 patients (12.8%) developed a cholestatic type of HCV recurrence and/or rapidly progressed to cirrhosis within 1 year. A multivariate binary regression analysis showed that HCV viremia at week 2 and a non-C/C recipient IL-28B genotype were independent risk factors for cholestatic recurrent HCV. No predictive factors could be found for the occurrence of recurrent liver cirrhosis 5 and 10 years after LT. Our study shows that the HCV RNA level at week 2 and the recipient IL-28B genotype are independent, statistically significant risk factors for post-LT cholestatic HCV, and it emphasizes the importance of viral load monitoring and IL-28B genotyping for identifying HCV recipients at risk for severe HCV recurrence.

Chromosomal imbalances in carcinoma showing thymus-like elements (CASTLE).

Carcinoma showing thymus-like elements (CASTLE) is a rare neoplasm of the thyroid gland resembling lymphoepithelioma-like and squamous cell carcinoma of the thymus and is thought to arise from ectopic thymic tissue within the thyroid gland or rudimentary branchial pouches along the thymic line. Using comparative genomic hybridization (CGH), chromosomal imbalances have been detected in several types of thymomas and thymic carcinomas. To evaluate whether there are hints of an underlying sequence in the pathogenesis of CASTLE analogue to those found in thymomas and thymic carcinomas, we evaluated four of these rare neoplasms for chromosomal imbalances using CGH. The most frequent gains were seen on chromosomal arm 1q (3/4), and losses were most frequently detected on 6p (4/4), 6q (3/4) and 16q (3/4). These CGH data show that CASTLE is characterized by chromosomal imbalances similar to those found in thymomas and thymic carcinomas and indicate a similar sequence in tumour development.

Comparison of real-time sonoelastography with T2-weighted endorectal magnetic resonance imaging for prostate cancer detection.

OBJECTIVES: The purpose of this study was to compare the value of real-time sonoelastography with T2-weighted endorectal magnetic resonance imaging (MRI) for prostate cancer detection. METHODS: Thirty-three patients with an elevated prostate-specific antigen level were investigated with real-time sonoelastography and T2-weighted endorectal MRI for prostate cancer diagnosis before systematic prostate biopsy. Real-time sonoelastography was performed to assess prostate tissue elasticity, and hard areas were considered suspicious for prostate cancer. Low-signal intensity nodules on T2-weighted endorectal MRI were considered suspicious for prostate cancer. Imaging findings were assigned to 6 areas of the peripheral zone (sextants), and their cancer detection rates were compared. RESULTS: Overall, prostate cancer was detected in 13 of 33 patients (39.4%). Both real-time sonoelastography and T2-weighted endorectal MRI detected 11 cancer-positive patients (84.6%). Real-time sonoelastography showed 27 suspicious lesions in 198 sextants, and 15 (55.6%) were cancer positive. T2-weighted endorectal MRI showed 31 suspicious lesions in 198 sextants, and 13 (40.6%) were cancer positive. These findings resulted in sensitivity rates and negative predictive values per patient of 84.6% and 86.7%, respectively, for sonoelastography and 84.6% and 83.3% for MRI. The per-sextant analysis showed sensitivity rates and negative predictive values of 57.7% and 93.6% for sonoelastography and 50.0% and 92.2% for MRI. CONCLUSIONS: Real-time sonoelastography showed comparable results as T2-weighted endorectal MRI for prostate cancer detection.

Handling and reporting of transurethral resection specimens of the bladder in Europe: a web-based survey by the European Network of Uropathology (ENUP).

AIMS: To collect of information about European practices on handling and reporting of transurethral resection specimens of the bladder. METHODS AND RESULTS: The European Network of Uropathology is a communication network that includes 335 pathology laboratories in 15 western European countries. A web-based questionnaire was answered by 52.2% of members. Some routines were adopted by a majority: formalin fixation (92.5%), separate containers for tumour and resection base (72%) and embedding of the entire specimen (60%). Cancer along/in adipose tissue would be reported as pT3a by 19.5% and non-invasive urothelial carcinoma in prostatic ducts/glands as pT4a by 16.1%. Papillary urothelial neoplasia of low malignant potential is recognized by 72.6% but rarely reported. Immunohistochemistry is rarely or sometimes used for diagnosing bladder cancer by 91.7%, and the most frequently used markers are CK20 (76.9%), CK7 (66.7%) and Ki67 (38.8%). Only 24.8% report prognostic markers, with Ki67 (84.4%) and p53 (64.4%) being most common. Only 50.9% use the International Society of Urological Pathology 1998/World Health Organization (WHO) 2004 grading system, followed by WHO 1973 (43.4%) and WHO 1999 (31.4%). CONCLUSIONS: There is still variability in routine practice and a need for standardization of methodologies. These results may be helpful when judging what recommendations are reasonable to issue.