Mika Sakaki

Double pituitary adenomas : six surgical cases

While double pituitary adenomas have been found in approximately 1% of autopsy pituitaries, those in surgically resected material have been only rarely reported. We report herein 6 cases of double pituitary adenomas, which consisted of two histologically and/or immunohistochemically different areas among approximately 450 surgical specimens. Five out of 6 patients were men and the age was ranged between 18 and 61 years old. All these 6 patients presented acromegaly or acrogigantism and hyperprolactinemia was noted in 3 patients. In 2 patients (cases 1 and 2) the two adenomas belonged to different adenoma groups (GH-PRL-TSH group and FSH/LH group), while in the remaining 4 patients (cases 3–6) the two adenomas belonged to the same group (GH-PRL-TSH group). Thus, in all patients at least one of the two adenomas was GH-producing adenoma. Reasons for a high incidence of GH-producing adenomas in surgically resected double pituitary adenomas may include the presence of a variety of histologic subtypes among GH-producing adenomas and the advantage of cytokeratin immunostaining to distinguish these subtypes. In regard to pathogenesis of double pituitary adenomas, adenomas in cases 1 and 2 may be of multicentric occurrence, while those in cases 3–6 may occur through different clonal proliferation within originally one adenoma, resulting in diverse phenotypic expressions. Since there were patients with familial MEN 1 (case 2) and familial pituitary adenoma unrelated MEN 1 (case 3), genetic background should be also considered. Double pituitary adenomas in surgically resected material may not be so infrequent. Further molecular analysis will provide new insights into understanding the pathogenesis of pituitary adenomas and their mechanisms of multidirectional phenotypic diffrentiation.

Immunohistochemical study of endocrine cells in ductal adenocarcinoma of the pancreas

Abstract. To clarify whether scattered endocrine cells in pancreatic ductal adenocarcinoma are neoplastic or not, we immunohistochemically studied 29 cases of invasive pancreatic ductal adenocarcinomas, 17 with metastases, for chromogranin A, insulin, glucagon, pancreatic polypeptide, serotonin, gastrin, laminin, and Ki-67. Endocrine cells were found in primary sites in 24 cases (82.3%), where endocrine cells showed at least a visibly close location to adjacent islet cells. Although endocrine cells in neoplastic glands were within the neoplastic basement membrane, endocrine cells were not seen in invasive sites beyond the pancreas where islets were not present. Endocrine cells in neoplastic glands were reactive for two or three of the islet hormones in all cases, and different types of hormonal reactivity was recognized in the same neoplastic gland or the same cluster of neoplastic glands in 22 (91.7%) cases, thus suggesting a close relation with islets. Ki-67 did not stain any endocrine cells in ten of the adenocarcinomas studied. In three (10.3%) cases, endocrine cells were found in the intraductal extensions. They may have pre-existed in non-neoplastic ducts. In 17 cases with metastatic sites, all but one had no endocrine cells in the metastases. Serotonin-positive cells were found in one metastatic lymph node in one case. We concluded that most endocrine cells seen in ductal adenocarcinomas of the pancreas are non-neoplastic and are derived from the surrounding islets. Some neoplastic endocrine cells may exist, though their frequency is low.

Gallbladder Adenocarcinoma with Florid Neuroendocrine Cell Nests and Extensive Paneth Cell Metaplasia

We report a unique case of gallbladder adenocarcinoma associated with florid neuroendocrine cell nests and extensive Paneth cell metaplasia that has not been described previously. The patient was a 79-yr-old woman with a pedunculated, polypoid mass in the gallbladder. Microscopically, the mass was composed of tumor cells showing tubular and papillary growth patterns, consistent with well-differentiated adenocarcinoma. One-third or more of the tumor cells showed Paneth cell appearance. Goblet cell-type tumor cells were also intermingled. In addition, neuroendocrine cell nests, that were connected to the neoplastic glands, were scattered throughout the stroma. Immunohistochemically, the labeling index of MIB-1 in adenocarcinoma cells including Paneth cell-type carcinoma cells was approx 40%. Neuron-specific enolase, chromogranin A, and synaptophysin were positive in the neuroendocrine cells forming solid nests and intermingled within neoplastic glands. They were immunopositive for serotonin but negative for insulin, glucagon, somatostatin, and pancreatic polypeptide (PP). Although MIB-1-positive neuroendocrine cell nests were very few with weak staining, we think that the neuroendocrine cell nests were neoplastic in nature. The formation of the multifocal neuroendocrine nests may be a consequence of the trophic effects of unknown substance(s), which can promote serotonin-producing neuroendocrine cells to proliferate. We postulate that Paneth cell-type carcinoma cells may be intimately related to such substance(s) in our case.

Unique cell membrane expression of topoisomerase-II alpha as a useful diagnostic marker of liposarcoma

Topoisomerase‐II alpha (Topo‐II alpha) is known as a cell cycle‐related intranuclear marker. To the best of our knowledge, the expression of Topo‐II alpha on extranuclear sites has not been reported. The aim of the present study was to determine the usefulness of Topo‐II alpha immunostaining for detecting the lipoblasts that are essential to diagnosing liposarcoma. Surgical specimens, including benign lipomatous tumors (four cases), well‐differentiated liposarcomas (three cases), myxoid liposarcomas (six cases), pleomorphic liposarcomas (two cases), dedifferentiated liposarcomas (two cases), myxoid malignant fibrous histiocytomas (six cases), and one case of mesenteric panniculitis, were studied. Samples were immunostained using antibodies for Topo‐II alpha, S‐100 protein and Ki‐67. In addition, we used the western blot method to investigate immunohistochemical‐affinity in adipocytes. Mature adipocytes and lipoblasts in all of the benign and malignant lipomatous tumors intensively expressed cell contours positivity for Topo‐II alpha. Cytoplasm of the lipoblasts occasionally reacted to the antibody and highlighted intracytoplasmic small unilocular, multivacuolated, or bubble‐like patterns. Western blot analysis confirmed a 70 kDa product reactive to Topo‐II alpha in the cell membrane fragment of mature adipocytes. S‐100 protein expressed adipocytes and lipoblasts, but the detection of lipoblasts was not as easy as in Topo‐II alpha immunostaining. Immunoreactivity of Ki‐67 was limited to the nuclei, and the nuclear labeling index of Ki‐67 correlated with that of Topo‐II alpha. The immunoreactivity of Topo‐II alpha for lipoblasts was more sensitive and obvious than those of S‐100 protein. Immunostaining using the antibody for Topo‐II alpha seems to be useful in recognizing lipoblasts that have been overlooked in hematoxylin–eosin‐stained preparations, and is a useful marker for diagnosing liposarcoma.

Retroperitoneal schwannoma is characterized by a high incidence of cellular type and GFAP-immunoreactivity.

To clarify the clinicopathologic characteristics of retroperitoneal schwannomas, which are sometimes confused with other spindle cell tumors, 27 cases were studied microscopically and immunohistochemically. The 27 cases consisted of 17 females and 10 males, the ages of whom ranged from 31–79 (mean 57.4) years. Gross examination revealed well‐demarcated, encapsulated tumors, 3–15 cm (mean 8 cm) in diameter. Microscopic review divided them into 13 cases of cellular/fascicular, 3 of conventional, 6 of intermediate, and 5 of ancient type. Cellular/fascicular schwannomas were composed of cellular fascicles of spindle cells, in which nuclear palisading, Antoni B area and cyst were unclear, while numerous foamy cells were intermingled. Immunohistochemical investigation revealed diffuse, strong positivity for S‐100 protein and Sox10 in all tumors studied. In addition, glial fibrillary acidic protein (GFAP) was extensively expressed in 92% of the cellular/fascicular type, while it was less prominent in others. The present study suggests that retroperitoneal schwannoma often occurs in the middle‐aged woman, grows to a large size, exhibits cellular/fascicular microscopic features in half of the cases, and may arise from GFAP‐positive Schwann cells. The presence of hyalinized vessels and dense infiltration of foamy macrophages as well as diffuse immunoreactivity for S‐100 protein and Sox10 are helpful for the differential diagnosis.

Vasitis nodosa: immunohistochemical findings--case report.

We report the immunohistochemical features of vasitis nodosa and discuss the differential diagnosis. The patient was a 42‐year‐old Japanese man with bilateral small indurations of the vas deferens at the site of a previous vasectomy. Microscopically, small‐sized ducts proliferated within the muscular wall of the vas deferens, and focally in the surrounding connective tissue. Immunohistochemically, most proliferating glandular cells were strongly positive for cytokeratins 7, 19, and 34βE12, and vimentin. Epithelial membrane antigen and Leu‐M1 reacted against the luminal surface of the cells. Focally, glandular cells were also positive for CA125. Cytokeratin 20, carcinoembryonic antigen, and prostate‐specific antigen were negative. We discuss the immunohistochemical differentiation of vasitis nodosa from prostatic adenocarcinoma, adenocarcinoma of the rete testis, and adenomatoid tumor.

Atypical teratoid rhabdoid tumor in the cavernous sinus of a toddler presenting with oculomotor nerve palsy

IntroductionAtypical teratoid rhabdoid tumor (ATRT) is a rare, highly malignant, and aggressive tumor of infancy. Although the prognosis of ATRT has been extremely poor, recently, the first prospective study for ATRT demonstrated improvement of prognosis. On the other hands, oculomotor nerve palsy is rare in children and the most frequent etiology is congenital. To our knowledge, only a few ATRT cases presenting with oculomotor nerve palsy have been reported, but ATRT originating from the cavernous sinus (CS) has not yet been reported.Case reportAn 18-month-old girl with right oculomotor nerve palsy was admitted, and a small mass in the right CS was detected with brain MRI. Although she received steroid pulse therapy and antimicrobial therapy, the mass continued to enlarge. One month after admission, the mass was partially resected and diagnosed as ATRT. Multimodal therapy including anthracycline-based chemotherapy, intrathecal therapy, and cranial irradiation was performed. Twenty-nine months after resection, she was alive without tumor relapse, but the oculomotor nerve palsy persisted.ConclusionThis is the first reported case of ATRT located in the CS presenting with oculomotor nerve palsy. This case was successfully treated with partial removal of the tumor, a new chemotherapy regimen for ATRT and cranial X-ray irradiation.

Ganglioneuroblastoma, intermixed with opsoclonus-myoclonus syndrome

Opsoclonus–myoclonus syndrome (OMS), also called ‘opsoclonus polymyoclonia syndrome’ or ‘dancing eyes syndrome’, is a rare condition characterized by rapid, involuntary, irregular movement of the eyeballs, myoclonus of the limbs and body trunk, and symptoms of cerebellar ataxia. The majority of OMS cases have neuroblastoma as a complication, while OMS is seen in only 2–3% of patients with neuroblastoma. In addition, in children, OMS is rarely seen as paraneoplastic syndrome. Infections are also seen in a small number of patients. The prognosis of patients with OMS complicated by neuroblastoma is generally said to be good, although the neurological prognosis is compromised. Neurological sequelae are said to include residual symptoms involving motor, language, and cognitive functions in 70–80% of patients with OMS. Steroids, corticotropin, immunosuppressants, Rituximab, and gammaglobulin are often used to treat those symptoms, but a standard therapeutic approach has not yet been established for OMS.

Malignant Myoepithelioma of the Sole: Abstracts

76-year-old man presented with a hen’s egg-sized elevated nodule in his left sole in 4/04. He had been hospitalized because of icterus since 3/04. Although cancer of the pancreatic head had been strongly suspected on the imaging, he had refused surgical operation. No metastasis of the cancer had been found on the imaging. A dermatologist who biopsied the nodule in his left plantar recognized the swelling of inguinal lymph nodes on the same side. Histologically medium sized oval cells formed solid nests in the dermis, rendering them lobulated appearance. Some of the nests showed myxoid change in the stroma where tumor cells often showed cord-like arrangement. The border with surrounding tissue was relatively clear. The cells had round, and often eccentrically located nuclei with one or two small nucleoli and moderate to scarce amount of eosinophilic cytoplasm. Mitosis was readily identifiable; >50/10HPF. Necrosis was not found. Immunohistochemically tumor cells were reactive for AE1/AE3, vimentin and S-100 protein and negative for ??SMA, CK14, EMA, HMB 45 and Melan A. MIB-1 labeling index was over 50%. The lesion was diagnosed as malignant myoepithelioma. The positivity for S-100 protein seen in this case necessitated us to differentiate it from melanoma.

15 Endocrine cells in invasive ductal adenocarcinoma of the pancreas: An immunohistochemical study

Endocrine cells are frequently observed in a wide variety of ordinary adenocarcinomas. In pancreatic ductal adenocarcinomas, scattered endocrine cells have been reported either to be lined up along the base of the neoplastic glands or to lie between the neoplastic columnar cells. They should be separated from endocrine cells in mixed ductal-endocrine carcinomas in which ductal and endocrine cells that compose at least one third to one-half of tumor tissue are intimately admixed in the primary tumors as well as in their metastasis. Endocrine cells in ductal adenocarcinomas might be neoplastic considering their close association with neoplastic glands. To clarify whether endocrine cells are neoplastic, the chapter discusses the localization of the endocrine cells in the primary, invasive, and metastatic sites of pancreatic invasive ductal adenocarcinomas by immunohistochemistry for chromogranin A, islet hormone (insulin, glucagon, and pancreatic polypeptide), serotonin, and gastrin. Most endocrine cells in pancreatic ductal adenocarcinoma are non-neoplastic and are derived from the surrounding islets, and there is a possibility that endocrine cells in the intraductal extensions are pre-existing non-neoplastic cells.