Composite hemangioendothelioma of the spleen with multiple metastases: CT findings and review of the literature.

ABSTRACT: Composite hemangioendothelioma (CHE) is a rare vascular neoplasm of intermediate malignant potential. Only 52 cases have been reported in the English literature, and one case previously reported occurred in the spleen. The purpose of our study was to report a 65-year-old man diagnosed as CHE primary arising from the spleen with multiple metastases.Clinical and imaging features, laboratory tests, and pathological results about CHE were described in detail in this study.The patient presented with multiple lesions in bilateral lungs and spleen that had been incidentally detected by computed tomography (CT). Except for thrombocytopenia, other laboratory tests were not significant. The CT scan of the abdomen revealed multiple round-like and irregularly mixed density masses with unclear borders in enlarged spleen. And contrast enhancement showed mild heterogeneous enhancement. CT scan also showed widespread liver, ribs, lungs, and vertebral bodies metastases. This diagnosis was confirmed by histopathological examination. The patient underwent splenectomy and still survives with tumors after six months followed-up.Due to the lack of specificity of clinical features and laboratory tests, it is necessary to combine imaging features and pathological findings to make a correct diagnosis.

Metastatic ovarian cancer spreading into mammary ducts mimicking an in situ component of primary breast cancer: a case report.

BACKGROUND: Accurate diagnosis of metastatic tumors in the breast is crucial because the therapeutic approach is essentially different from primary tumors. A key morphological feature of metastatic tumors is their lack of an in situ carcinoma component. Here, we present a unique case of metastatic ovarian carcinoma spreading into mammary ducts and mimicked an in situ component of primary carcinoma. To our knowledge, this is the second case (and the first adult case) confirming the in situ-mimicking growth pattern of a metastatic tumor using immunohistochemistry. CASE PRESENTATION: A 69-year-old Japanese woman was found to have a breast mass with microcalcifications. She had a known history of ovarian mixed serous and endocervical-type mucinous (seromucinous) carcinoma. Needle biopsy specimen of the breast tumor revealed adenocarcinoma displaying an in situ-looking tubular architecture in addition to invasive micropapillary and papillary architectures with psammoma bodies. From these morphological features, metastatic serous carcinoma and invasive micropapillary carcinoma of breast origin were both suspected. In immunohistochemistry, the cancer cells were immunoreactive for WT1, PAX8, and CA125, and negative for GATA3, mammaglobin, and gross cystic disease fluid protein-15. Therefore, the breast tumor was diagnosed to be metastatic ovarian serous carcinoma. The in situ-looking architecture showed the same immunophenotype, but was surrounded by myoepithelium confirmed by immunohistochemistry (e.g. p63, cytokeratin 14, CD10). Thus, the histogenesis of the in situ-like tubular foci was could be explained by the spread of metastatic ovarian cancer cells into existing mammary ducts. CONCLUSION: Metastatic tumors may spread into mammary duct units and mimic an in situ carcinoma component of primary breast cancer. This in situ-mimicking growth pattern can be a potential pitfall in establishing a correct diagnosis of metastasis to the breast. A panel of breast-related and extramammary organ/tumor-specific immunohistochemical markers may be helpful in distinguishing metastatic tumors from primary tumors.

Gastrointestinal mixed adenoneuroendocrine carcinoma (MANEC): An immunohistochemistry study of 13 microsatellite stable cases.

BACKGROUND: Mixed adenoneuroendocrine carcinoma (MANEC) is currently included in the category of neuroendocrine carcinomas but the therapeutically management is not yet defined. AIMS: To present the immunohistochemical (IHC) features of the epithelial mesenchymal transition (EMT) of MANEC. MATERIALS AND METHODS: The clinicopathological features of 13 consecutive cases of MANEC (6 gastric and 7 colorectal) were correlated with the IHC expression of the biomarkers E-cadherin, ß-catenin, N-cadherin, vimentin, maspin, CD44 and S100. In all of the cases open surgery was performed. RESULTS: All of the cases showed microsatellite stable status, expressed E-cadherin and membrane ß-catenin in both components (neuroendocrine and adenocarcinoma) and were negative for N-cadherin, vimentin and S-100. The colorectal MANECs were negative for maspin. In gastric MANECs, maspin showed cytoplasm positivity in the neuroendocrine component and nuclear translocation in the adenocarcinoma cells. CD44 was positive in all of the cases, in both components. No tumor buddings were identified. Three of the 13 patients survived for at least 32 months, all of them showing lymphatic emboli but not lymph node metastases. Pure neuroendocrine lymph node metastases were seen in only four of the cases: one from stomach, two of the ascending colon and two cases of the upper rectum. CONCLUSIONS: Gastrointestinal MANEC is a microsatellite stable tumor with nodular growth, which components might originate from a CD44-positive stem-like precursor cell. Lymph node status remains the most reliable prognostic parameter and agressivity seems to not be influenced by tumor budding degree or EMT-related features. The histologic aspect of metastatic component (neuroendocrine versus adenocarcinoma) should be included in the histopathological reports and might be used for establishing the proper-targeted therapy of MANEC.

The Clinical Significance of a Small Component of Choriocarcinoma in Testicular Mixed Germ Cell Tumor (MGCT).

The clinical significance of limited choriocarcinoma in a malignant mixed germ cell tumor (MGCT) is unknown. Men with a MGCT with ≤5% choriocarcinoma at radical orchiectomy (RO) between 2000 and 2016 from our consult service were studied. Of 50 men in our cohort, we had clinical information for 30 men. Median follow-up was 41 months (1 to 168 mo). Median tumor size was 4.5 cm (1.1 to 8.0 cm). In total, 22/30 (73%) cases were pT1, 6/30(20%) cases were pT2, and 2/30 (7%) cases were pT3. In total, 4/30(13%) cases had lymph node metastases and 2/30 (7%) cases had distant metastases at the time of RO. In 30 cases with RO we had information on immediate postorchiectomy treatment: 14/30 (46.7%) active surveillance, 4/30 (13.3%) retroperitoneal lymph node dissection, 10/30 (33.3%) chemotherapy (chemotherapy), 1/30 (3.3%) retroperitoneal lymph node dissection followed by chemotherapy, and 1/30 (3.3%) resection of a distant metastasis. Preoperative serum human chorionic gonadotropin (hCG) levels ranged between 0.1 and 60,715 mIU/mL (mean, 4796; median, 485). One patient had an hCG level of 6367 mIU/mL and another 60,715 mIU/mL with the remaining cases <5000 mIU/mL. In total, 4/30 (13%) patients had elevated serum markers after surgery, 3 of them normalized following chemotherapy while the fourth one continued to have elevated serum alpha fetoprotein levels after chemotherapy. All patients were alive at last follow-up. In total, 7/30 (23.3%) patients subsequently developed metastatic disease to lymph nodes or distal organs, the histology of the metastasis consisted mainly of teratoma and yolk sac tumor. Embryonal carcinoma was present in 2 metastatic sites. One lung metastasis was suggestive for choriocarcinoma. Definitive choriocarcinoma was not present in any of the metastasis. A small component of choriocarcinoma in a MGCT is typically associated with relatively low-level elevations of serum hCG levels, and is not associated with aggressive disease. The presence of limited choriocarcinoma (≤5%) does not add to the prognostic information provided by standard TNM staging, which uses levels of serum markers (hCG, alpha fetoprotein, lactate dehydrogenase) as surrogates for extent of disease.

Clinical Outcome of Retroperitoneal Lymph Node Dissection after Chemotherapy in Patients with Pure Embryonal Carcinoma in the Orchiectomy Specimen.

OBJECTIVE: To determine the pathologic findings and clinical outcome of patients with pure embryonal carcinoma (EC) of the testis who were diagnosed with testis cancer from January 1989 to January 2013 who underwent an orchiectomy, cisplatin-based chemotherapy and a postchemotherapy retroperitoneal lymph node dissection (PC-RPLND). METHODS: We compared those patients with 100% EC with those with mixed nonseminomatous germ cell tumor pathology who underwent a PC-RPLND. RESULTS: Of 1105 patients who underwent a PC-RPLND, 145 had pure EC. Twenty-six percent of patients presented with metastatic disease outside the retroperitoneum. Patients with mixed histologies tended to have worse International Germ Cell Cancer Collaborative Group risk compared to those with EC at orchiectomy (P = .037). Histology at PC-RPLND revealed fibrosis or necrosis in 76%, mature teratoma in 19% and viable cancer in 4%. Over one-third of the patients had a residual mass of <1 cm prior to RPLND; of whom 15% harbored mature teratoma in PC-RPLND histology. The Kaplan-Meier estimated probability of recurrence at 5 years of follow-up was 3.1% (95% CI 1.2%, 8.0%) for EC histology, 7.3% lower than mixed histology. For cancer-specific mortality, the Kaplan-Meier estimated probability at 5 years was 4.6% (95% CI 3.3%, 6.3%) and 1.7% (95% CI 0.4%, 6.8%) for mixed and pure EC histologies, respectively. CONCLUSION: Approximately 20% of patients with pure EC had teratoma at PC-RPLND. We have shown that those with a maximum node size of <1 cm should not be precluded from RPLND.

Differential analysis of lymph node metastasis in histological mixed-type early gastric carcinoma in the mucosa and submucosa.

AIM: To investigate the relationship between histological mixed-type of early gastric cancer (EGC) in the mucosa and submucosa and lymph node metastasis (LNM). METHODS: This study included 298 patients who underwent gastrectomy for EGC between 2005 and 2012. Enrolled lesions were divided into groups of pure differentiated (pure D), pure undifferentiated (pure U), and mixed-type according to the proportion of the differentiated and undifferentiated components observed under a microscope. We reviewed the clinicopathological features, including age, sex, location, size, gross type, lymphovascular invasion, ulceration, and LNM, among the three groups. Furthermore, we evaluated the predictors of LNM in the mucosa-confined EGC. RESULTS: Of the 298 patients, 165 (55.4%) had mucosa-confined EGC and 133 (44.6%) had submucosa-invasive EGC. Only 13 (7.9%) cases of mucosa-confined EGC and 30 (22.6%) cases of submucosa-invasive EGC were observed to have LNM. The submucosal invasion (OR = 4.58, 95%CI: 1.23-16.97, P = 0.023), pure U type (OR = 4.97, 95%CI: 1.21-20.39, P = 0.026), and mixed-type (OR = 5.84, 95%CI: 1.05-32.61, P = 0.044) were independent risk factors for LNM in EGC. The rate of LNM in mucosa-confined EGC was higher in the mixed-type group (P = 0.012) and pure U group (P = 0.010) than in the pure D group, but no significant difference was found between the mixed-type group and pure U group (P = 0.739). Similarly, the rate of LNM in the submucosa-invasive EGC was higher in the mixed-type (P = 0.012) and pure U group (P = 0.009) than in the pure D group but was not significantly different between the mixed-type and pure U group (P = 0.375). Multivariate logistic analysis showed that only female sex (OR = 5.83, 95%CI: 1.64-20.70, P = 0.028) and presence of lymphovascular invasion (OR = 13.18, 95%CI: 1.39-125.30, P = 0.020) were independent risk factors for LNM in mucosa-confined EGC, while histological type was not an independent risk factor for LNM in mucosa-confined EGC (P = 0.106). CONCLUSION: For mucosal EGC, histological mixed-type is not an independent risk factor for LNM and could be managed in the same way as the undifferentiated type.

Cutaneous Apocrine Carcinoma With an In Situ Component and Histiocytoid and Signet-Ring Cells.

We present a case of cutaneous apocrine carcinoma arising in the axilla of a 71-year-old man. The tumor had a significant component of histiocytoid and signet-ring cells as well as in situ carcinoma within the apocrine glands. The cells expressed GATA3, gross cystic disease fluid protein 15, androgen receptor, and E-cadherin. Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 were negative. Clinical correlation was required to rule out a metastasis from the breast or the gastrointestinal tract. Although most cutaneous apocrine carcinomas do not behave aggressively, our patient developed bone metastases and eventually died of his disease. It is debated whether histiocytoid and signet-ring cell cutaneous carcinomas should be classified as apocrine neoplasm. The presence of in situ carcinoma associated with this kind of tumor has been reported only once in the literature. This characteristic and the immunohistochemical profile are in favor of apocrine differentiation.

Primary combined small cell carcinoma and squamous cell carcinoma of the oropharynx with special reference to EGFR status of small cell carcinoma component: Case report and review of the literature.

Combined small cell carcinoma (SCC) and squamous cell carcinoma (SqCC) of the oropharynx is extremely rare and shows an aggressive clinical course. There are only 5 reported cases of combined SCC and SqCC in the English language literature. Here, we report a 59-year-old male presenting with a right tonsillar mass. The mass was biopsied, and the histological findings showed a proliferation of small-sized tumor cells with scant cytoplasm. Immunohistochemically, the tumor cells were positive for neuroendocrine markers (synaptophysin, chromogranin A, and CD56). Our first diagnosis was tonsillar small cell carcinoma. We treated the patient with concurrent chemoradiotherapy together with cisplatin followed by surgery. The resected tonsillar specimen showed a residual tumor composed of SCC and SqCC, and lymph nodes showed metastatic tumor cells of the SCC component. Immunohistochemically, the SCC component was positive for all neuroendocrine markers and p16; on the other hand, the SqCC component was positive for p40, p63, p16, and EGFR. Fluorescence in situ hybridization revealed that neither component showed any EGFR gene copy number gain. The patient was treated with adjuvant chemotherapy consisting of irinotecan and cisplatin. Liver and bone metastases developed, resulting in the death of the patient. We discuss the present case and review similar cases. Most cases of combined SCC and SqCC occur regardless of p16 status, and a therapeutic strategy has yet to be determined. Further examination of this kind of combined tumor is necessary.

Role of High-Dose Chemotherapy With Autologous Stem-Cell Rescue in Men With Previously Treated Germ Cell Tumors.

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 39-year-old, previously healthy man presented with a left testicular mass, confirmed on ultrasound. He underwent left inguinal orchiectomy, which disclosed testicular carcinoma composed of 90% choriocarcinoma, 9% seminoma, and 1% teratoma. Imaging revealed numerous metastases in the lungs, liver, and brain. Prechemotherapy levels of serum tumor markers were alpha-fetoprotein (AFP) 2.0 ng/mL, human chorionic gonadotropin (hCG) 151,111 IU/L, and lactate dehydrogenase 588 U/L. He received four courses of etoposide, ifosfamide, and cisplatin chemotherapy, given without bleomycin because of the anticipated need for postchemotherapy thoracic surgery. He had an incomplete response to induction chemotherapy. The serum hCG level was 8.1 IU/L, and there were residual lesions in the liver and lungs whereas the brain metastases had nearly resolved. His Eastern Cooperative Oncology Group performance status was zero. He had no symptoms of ototoxicity or peripheral neurotoxicity. Repeat serum hCG levels after chemotherapy were 12.3 IU/L at 2 weeks and 325 IU/L at 4 weeks. He was referred to discuss optimal ongoing treatment.

Nonchoriocarcinomatous Trophoblastic Tumors of the Testis: The Widening Spectrum of Trophoblastic Neoplasia.

Tumors of trophoblastic derivation other than choriocarcinoma are very rare in the testis but have been reported on occasion in association with other germ cell tumors. Their morphologic spectrum is analogous to the trophoblastic tumors of the female genital tract including epithelioid trophoblastic tumor (ETT) and placental site trophoblastic tumor (PSTT). Herein we report our experience with 8 cases of trophoblastic tumors of testicular origin that lacked the features of choriocarcinoma; these included 4 ETTs, 1 PSTT, 1 unclassified trophoblastic tumor (UTT), 1 partially regressed choriocarcinoma with a monophasic morphology, and 1 hybrid tumor showing a mixture of adenocarcinoma and a UTT. All tumors occurred in young men 19 to 43 years old. Five arose de novo within the testis (2 ETTs, 1 UTT, 1 regressing choriocarcinoma, and the hybrid tumor) as a component of mixed germ cell tumors, and 3 (2 ETTs and 1 PSTT) were found in metastatic sites after chemotherapy. The trophoblastic component was minor (5% to 10%) in 6 tumors but was 95% of 1 metastatic tumor (ETT) and 50% of the hybrid tumor. Other germ cell tumor elements were identified in all cases, most commonly teratoma. The ETTs consisted of nodules and nests of squamoid trophoblast cells showing abundant eosinophilic cytoplasm, frequent apoptotic cells, extracellular fibrinoid material, and positivity for p63 and negativity for human placental lactogen (HPL). The PSTT showed sheets of discohesive, pleomorphic, mononucleated trophoblast cells that invaded blood vessels with fibrinoid change and were p63 negative and HPL positive. The UTT showed a spectrum of small and large trophoblast cells, some multinucleated but lacking distinct syncytiotrophoblasts, and was patchily positive for both p63 and HPL. The hybrid tumor had ETT-like and adenocarcinomatous areas that coexpressed inhibin and GATA3 but were negative for p63 and HPL, leading to classification of the trophoblastic component as UTT. Seven of the patients were alive and well on follow-up (8 to 96 mo; median, 39 mo), whereas the patient with the hybrid tumor died of liver metastases at 2 years. Our study verifies that trophoblastic neoplasms often having the features of nonchoriocarcinomatous gestational trophoblastic tumors may arise from the testis, occur either in the untreated primary tumor or in metastases after chemotherapy, and should be distinguished from choriocarcinoma given what appears to be a less aggressive clinical course.

Mixed Epithelial and Stromal Tumor of the Kidney with Sarcomatous Transformation Metastatic to the Lung. A Case Report.

BACKGROUND: Malignant transformation of mixed epithelial and stromal tumor (MEST) of the kidney is a very rare entity. We report an unusual case with a review of the literature. CASE: A 25-year-old woman underwent surgery for an 8-cm biphasic renal tumor, which was diagnosed as MEST of the kidney. High cellularity, mitoses, and nuclear atypia seen in the stromal component were compatible with a sarcomatous transformation in MEST. The patient also had pulmonary metastatic nodules that were resected 2 months after the nephrectomy. Metastatic pulmonary tumors were morphologically identical to the sarcomatous component of the renal tumor and showed pulmonary epithelial hyperplasia with a phyllodes-like pattern. CONCLUSION: Although MEST of the kidney is known as a benign tumor, malignant transformation, mostly sarcomatous type, should be considered in the diagnosis.

Discrepancies in the histologic type between biopsy and resected specimens: a cautionary note for mixed-type gastric carcinoma.

AIM: To evaluate discrepancies between biopsy and resected specimens using the Japanese Classification of Gastric Carcinoma (JCGC) and tumor-node-metastasis (TNM) classification. METHODS: A total of 376 consecutive paired samples from biopsy and resected gastric specimens, which were derived from curative gastrectomy for gastric cancer between 2008 and 2011, were retrospectively analyzed. RESULTS: (1) Discrepancies in the histologic type were observed between biopsy and resected specimens; 11.7% (44/376) in the JCGC and 18.1% (68/376) in TNM. In specimens diagnosed as the differentiated type from biopsy specimens, 14.4% (28/195) in the JCGC and 41.1% (67/163) in TNM were finally diagnosed as the undifferentiated type from resected specimens; and (2) the incidence of mixed-type gastric cancer was significantly higher in specimens with discrepancies than in those without in both the JCGC and TNM (both P < 0.0001); 93.2% (41/44) of specimens with discrepancies in the JCGC and 97.1% (66/68) of specimens with discrepancies in TNM were mixed-type gastric cancers. CONCLUSION: Mixed-type gastric cancer was associated with a high incidence of histologic discrepancies between biopsy and resected specimens in both the JCGC and TNM definitions. Care should be taken in deciding treatments based on diagnosis of the histologic type for mixed-type gastric cancer from biopsy specimens.

Mixed adenoneuroendocrine carcinoma of gastrointestinal tract: report of two cases.

Mixed adenoneuroendocrine carcinoma (MANEC) is a rare tumor of the gastrointestinal tract that consists of a dual adenocarcinomatous and neuroendocrine differentiation, each component representing at least 30% of the tumor. To date, only seven cases have been reported in the cecum, and less than 40 in the stomach. Our first case was diagnosed in a 74-years-old female as a polypoid lesion of the cecum with direct invasion in the transverse colon, without lymph node metastases. The second case was diagnosed in the stomach of a 46-years-old male as a polypoid tumor of the antral region that invaded the pancreas and presented metastases in 22 regional lymph nodes. The metastatic tissue was represented by the glandular component. In both cases, the tumor consisted of a moderately-differentiated tubular adenocarcinoma (with mucinous component in Case 1) intermingled with neuroendocrine carcinoma. Ki67 index was lower than 20% in Case 1, respectively higher than 20% in Case 2. The neuroendocrine component was marked by synaptophysin and neuron specific enolase, being negative for Keratins 7/20. The neuroendocrine component represented 60% in Case 1, and 40% in Case 2, respectively. The glandular components were marked by carcinoembryonic antigen, maspin and keratin 20/7 (Case 1/2). Both cases were proved to be microsatellite stable. Independently by the localization and tumor stage, MANECs appear to be highly malignant tumors, with high risk for distant metastases. The aggressiveness seems to depend on the endocrine component, independent of its proportion. The neuroendocrine component could be a dedifferentiated adenocarcinoma with a neuroendocrine phenotype.

Neuroendocrine liver metastasis in gastric mixed adenoneuroendocrine carcinoma with trilineage cell differentiation: a case report.

Mixed adenoneuroendocrine carcinoma (MANEC) is a rare disease, which mostly occurs in the gastrointestinal tract and pancreas. Here we report a case of gastric MANEC with tri-lineage differentiation in which only the neuroendocrine component had metastasized to the liver. Liver and gastric masses were detected by abdominal computed tomography, and the preoperative relationship between liver and gastric masses was unknown. The histopathological analysis after operation confirmed the gastric mass to be MANEC, whereas the liver mass was actually the metastatic neuroendocrine component of the gastric MANEC. In the pathologic diagnosis, tri-lineage differentiation, including tubular adenocarcinoma, neuroendocrine carcinoma and squamous cell carcinoma was observed in the gastric MANEC tissues. The mitotic and Ki-67 labeling indexes of the resected tumor tissue were high, and thus, the tumor was classified as a grade G3 neuroendocrine carcinoma, which has a poor prognosis. Multiple low-density masses were found in the right lobe of the liver 2.5 months after operation.

Mixed adenoneuroendocrine carcinoma of the colon progressed rapidly after hepatic rupture: report of a case.

The rupture of a metastatic mixed adenoneuroendocrine carcinoma (MANEC) has not been previously reported, although the neuroendocrine cell carcinoma is often associated with a high incidence of hepatic metastases. The patient was a 39-year-old male who presented with upper abdominal pain over 3 months. Computed tomography showed multiple tumors in both hepatic lobes, while lower gastrointestinal endoscopy revealed a tumor in the transverse colon. Histopathologic examination of the tumor revealed it to be a neuroendocrine cell carcinoma. After the resection of the primary tumor, hepatic metastases rapidly increased, and one of them in the left lateral segment was ruptured with significant hemorrhage. The rupture led us to undertake the emergency operation to stop the bleeding. Histology showed a high-grade large-cell neuroendocrine carcinoma associated with moderately differentiated tubular adenocarcinoma. The Ki-67 labeling index was 80% (G3). The diagnosis was mixed adenoneuroendocrine carcinoma according to the 2010 World Health Organization guidelines. Hepatic arterial infusion chemotherapy, systemic chemotherapy, and transcatheter arterial chemoembolization did not decrease the tumor progress, and the patient died on postoperative day 110. Reporting this highly malignant case, I hope all doctors can be interested in MANEC.

Clinicopathologic analysis of choriocarcinoma as a pure or predominant component of germ cell tumor of the testis.

Although well recognized in the literature, the contemporary clinicopathologic data regarding choriocarcinoma (CC) as a pure or the predominant component of a testicular germ cell tumor (GCT) are limited. Herein, we present a series of pure CC and predominant CC in mixed GCT of the testis obtained from a single oncology institution. A comprehensive histologic review of 1010 orchiectomies from 1999 to 2011 yielded 6 (0.6%) pure CC and 9 (0.9%) mixed GCT cases with a predominant CC component. Patients' ages ranged from 20 to 39 years (median 29 y). All patients had markedly elevated serum ß-hCG levels (median 199,000 IU/mL) at presentation. All tumors were unilateral and involved the right (9/15) and left (6/15) testis. The mean tumor size was 6.5 cm (range, 1.5 to 8 cm). Histology was similar for pure CCs and the CC component of mixed GCTs. CC commonly showed expansile hemorrhagic nodular cysts surrounded by variable layers of neoplastic trophoblastic cells (mononucleated trophoblasts and syncytiotrophoblasts). The syncytiotrophoblasts usually covered columns of mononucleated trophoblasts and occasionally formed plexiform aggregates and pseudovillous protrusions. Immunohistochemical stains suggested a mixture of cytotrophoblasts (p63+, HPL_) and intermediate trophoblasts (p63-, HPL weak +/-) in the columns of mononucleated cells. In the 9 mixed GCTs, CC comprised 50% to 95% (7/9 were ≥80% CC) of the tumor; 7 were combined with 1, and 2 were combined with 2 other GCT components. The non-CC components included teratoma (5/9), seminoma (2/9), yolk sac tumor (2/9), and embryonal carcinoma (2/9). Lymphovascular invasion, spermatic cord invasion, and tunica vaginalis invasion were present in 15/15, 5/15, and 1/12 cases, respectively. In mixed GCTs, these locally aggressive features were attributed to the CC component, except in 1 tumor in which it was also exhibited by the embryonal carcinoma component. Lymphovascular invasion was multifocal to widespread in 73% of tumors. The stages of the 15 tumors were: pT2 (10), pT3 (5); NX (1), N1 (4), N2 (5), N3 (5); and M1a (2) and M1b (13). Distant organ metastasis mostly involved the lungs (11) and liver (10). Follow-up information was available in 14 patients, all of whom received cisplatin-based chemotherapy. All 6 pure CC patients were dead of disease (range, 6 to 14 mo, median 9.5 mo). Follow-up of 8 patients with predominant CC (range, 10 to 72 mo, median 27 mo) showed that 5 died of the disease, and 1 was alive with disease and 2 were alive with no evidence of disease at 60 and 72 months of follow-up, respectively; these latter 2 patients were the only ones with M1a disease on presentation. This series confirms the proclivity for high-stage presentation including presence of distant metastasis, hematogenous spread, and poor outcome of testicular CC. Mixed GCT with a predominant CC component has similar tendency for high-stage presentation, marked elevation of serum ß-hCG levels, and aggressive behavior compared with pure CC. This study also showed that distant metastasis by CC when only involving the lungs (M1a) may not be uniformly fatal with chemotherapy. The mononucleated trophoblastic columns in testicular CC appear to be a mixture of cytotrophoblasts and intermediate trophoblasts, similar to that described in gestational CC.

A rare case of primary choriocarcinoma in the sigmoid colon.

Primary colorectal choriocarcinoma is an extremely rare neoplasm and is usually associated with a poor prognosis. Only 13 cases of colorectal choriocarcinoma have previously been reported. There is no standard chemotherapeutic regimen for this tumor type. A 68-year-old man presented with melena and was diagnosed with sigmoid colonic adenocarcinoma with multiple liver metastases. He underwent a laparoscopic sigmoidectomy. Pathology revealed choriocarcinoma with a focal component of moderately differentiated adenocarcinoma of colon origin. Based on the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) results, mFOLFOX6 and bevacizumab were administered, which suppressed aggressive tumor growth for 4 mo. The patient died 9 mo after the initial diagnosis. Our study results suggest that the standard chemotherapy regimen for colorectal cancer might have suppressive effects against primary colorectal choriocarcinoma. Moreover, CD-DST may provide, at least in part, therapeutic insight for the selection of appropriate antitumor agents for such patients.

Mucinous tubular and spindle cell carcinoma of the kidney with sarcomatoid transformation.

Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney is a recently described entity in the World Health Organization (WHO) 2004 classification and has a relatively indolent behavior. Sarcomatoid differentiation has been well documented in most histologic variants of renal cell carcinoma and its presence is known to have a worse prognosis. Its occurrence in an otherwise benign MTSCC is extremely rare. Here, we report a unique case of MTSCC in a 64-year-old patient with multiple areas of high-grade spindle cells and large areas of necrosis in it. The patient had a rapidly fatal clinical outcome.

Molecular genetic evidence supporting the origin of somatic-type malignancy and teratoma from the same progenitor cell.

Occasionally, testicular teratomas have been observed to occur in association with somatic-type malignancies. The latter may be seen in the primary germ cell tumor or, more commonly, in metastases after chemotherapy. The molecular-genetic relationship between the teratoma and the somatic-type malignancy is uncertain. We examined 27 pairs of teratoma and somatic-type malignancies in metastatic lesions. Interphase fluorescence in situ hybridization (FISH) analysis for 12p overexpression and i(12p) was performed on formalin-fixed, paraffin-embedded specimens. In addition, we compared the pattern of allelic loss between the teratoma and the somatic-type malignancy using 4 microsatellite DNA markers (D1S508, interferon-α, D13S317, and D18S543). A laser capture microdissection technique was used to procure separate tumor components. The somatic-type malignancies included adenocarcinoma (13), primitive neuroectodermal tumor (5), sarcoma not otherwise specified (5), squamous cell carcinoma (1), chondrosarcoma (1), and rhabdomyosarcoma (2). Twenty-one of 27 tumor pairs (78%) showed a similar pattern of overexpression of 12p and/or i(12p) in both components. Two of the 27 (7%) tumor pairs showed i(12p) only in the teratomatous component, and 4 of the 27 (15%) tumor pairs showed no abnormalities of chromosome 12p by interphase FISH. Eight of the 12 (67%) tumor pairs analyzed had identical patterns of loss of heterozygosity in both the teratoma and the somatic-type malignancy. Four of the 12 (33%) paired cases showed additional allelic loss at the interferon-α locus in the somatic-type malignant component only. Our data show that the somatic-type malignancies that develop in germ cell tumors have the same genetic alterations, detectable by FISH and loss of heterozygosity studies, as in the corresponding teratoma. These findings support that the somatic-type malignancies within metastases and the teratomas are clonally related and likely derived from a common progenitor cell. Interphase FISH can be performed on formalin-fixed, paraffin-embedded tissue and is a sensitive method for detecting 12p overexpression and i(12p), thus aiding in establishing the germ cell origin of somatic-type malignancies in this context.