Akiko Hino

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.

Imprint cytology of epithelioid angiomyolipoma in a patient with tuberous sclerosis. A case report.

BACKGROUND Angiomyolipoma composed predominantly of epithelioid cells has been referred to as epithelioid angiomyolipoma. As this subtype shows considerable cellular atypia, it may be erroneously diagnosed as malignant epithelioid tumor, such as renal cell carcinoma and hepatocellular carcinoma. So far, only one report describing the cytologic findings of epithelioid angiomyolipoma has been documented, and epithelioid angiomyolipoma occurring in the peritoneal cavity has not been reported. CASE Eleven years after resection of a renal epithelioid angiomyolipoma in a 34-year-old male with tuberous sclerosis, a tumor appeared in the peritoneal cavity and three masses in the liver. The intraoperative smears imprinted from part of the peritoneal mass revealed many large, atypical cells. The well-preserved atypical cells showed abundant, round to polyhedral, granular cytoplasm. Bizarre, giant nuclei with hyperchromasia and huge nucleoli were occasionally seen. Intranuclear cytoplasmic inclusions and mitotic figures were occasionally observed. As the epithelioid cells were markedly pleomorphic, we could not rule out hepatocellular carcinoma, cytologically and histologically, in the intraoperative consultation. In permanent sections the tumor was composed predominantly of epithelioid cells showing an alveolar pattern or sheetlike arrangement. Mitotic counts were zero to one per 10 high-power fields. Immunohistochemically, the epithelioid tumor cells were positive for vimentin, alpha-smooth muscle actin and HMB-45, consistent with epithelioid angiomyolipoma. MIB-1-labeling index was 1.6%. CONCLUSION When one sees atypical epithelioid tumor cells in a tuberous sclerosis patient during an intraoperative consultation, one must consider epithelioid angiomyolipoma.

“Honeycomb Golgi” in pituitary adenomas: Not a marker of gonadotroph adenomas

The vacuolar change in Golgi complexes known as “honeycomb Golgi” has been described as the ultrastructural hallmark of a specific tumor that has been called the “female gonadotroph” adenoma of the human pituitary. Recently, a few adenomas presenting with Cushing’s disease have been reported to exhibit this feature. To clarify the significance of a “honeycomb Golgi” in the classification of pituitary adenomas, we studied clinically nonfunctioning adenomas with or without “honeycomb Golgi” using immunohistochemistry for adenohypophysial hormones and RT-PCR for the cell-specific transcription factors Tpit that identifies corticotrophs and SF-1 that identifies gonadotrophs. All adenomas were from women. Among 20 adenomas with complete “honeycomb Golgi” change, gonadotrophin subunits were totally immunonegative, but ACTH was positive in a few cells of 12 adenomas. Among eight adenomas with partial vacuolar change of the Golgi complex, five were positive for gonadotrophins and two were positive for ACTH. A subgroup of these lesions were examined by RT-PCR and among eight adenomas with typical “honeycomb Golgi” one case expressed both Tpit and SF-1, probably due to contamination with normal pituitary and another expressed neither Tpit nor SF-1. Of the remaining six cases, Tpit was expressed in two cases and SF-1 in four. These findings indicate that “honeycomb Golgi” change can been seen in corticotroph adenomas as well as gonadotroph adenomas. The reason why this vacuolar change occurs only in females remains to be clarified.

Adenosarcoma of the uterine cervix presenting as a cervical polyp

A case of adenosarcoma arising from the uterine cervix of a 55‐year‐old female who complained of vaginal discharge is reported. A polyp, 6 × 2 × 1.5 cm in size, Identified in the cervical canal was clinically diagnosed as benign cervical polyp and resected. Histologically, the polyp was composed of benign epithelial components and sarcomatous stroma wherein periglandular hypercellularity and some mitoses including atypical ones were noted. Immunohistochemi‐cally, stromal cells were positive for muscle‐type actins, desmin and estrogen receptor. Adenosarcoma is a rare, blphasic tumor of the uterus and usually presents as a polypoid mass in the endometrial cavity. When they arise from the cervix, adenosarcomas may be confused with benign cervical polyps clinically and pathologically. As the former often recurs, microscopic dlfferentlatlon is crucial for further treatment.

p53 gene mutation in N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary bladder tumors and N-methyl-N-nitrosourea-induced colon tumors of rats

We analyzed p53 mutations in 17 N-butyl-N-(4-hydroxybutyl) nitrosamine-induced bladder transitional cell carcinomas (TCCs) with or without areas of squamous cell carcinoma (SCC) of Long-Evans Cinnamon (LEC) and F344 rats, and in 7 N-methyl-N-nitrosourea-induced colon adenocarcinomas of LEC rats by polymerase chain reaction-single strand conformation polymorphism analysis and DNA sequencing. Of these bladder tumors, one TCC with moderately differentiated SCC had a T to G transversion mutation at codon 141, leading to a Val to Gly amino acid change. No p53 mutation was found in colon adenocarcinomas. Thus a p53 gene mutation seems infrequent in these rat bladder and colon carcinogenesis models even in the late stage.

Effects of tacrolimus (FK506) on induction of glutathione S-transferase P-positive foci and liver cell regeneration after partial hepatectomy in F344 rats

The effects of FK506, a potent immunosuppressive drug, on hepatocarcinogenesis were investigated using a medium-term liver bioassay model based on the induction of glutathione S-transferase placental form (GST-P)-positive preneoplastic foci and by studies on liver cell regeneration after two-thirds partial hepatectomy (PH). In Experiment 1, daily FK506 administration, 0.5 or 1.0 mg kg−1 by gastric intubation, increased the areas of GST-P-positive foci in male F344 rats (P<0.05). In Experiment 2, FK506 treatment increased the hepatic 5-bromo-2-deoxyuridine labeling indices on day 1 (P<0.05) and day 2 after PH and the liver weight on day 7 (P<0.01). These results suggest that FK506 has a weak enhancing effect on hepatocarcinogenesis and accelerates liver cell proliferation after hepatectomy.

Invasive pituitary adenoma protruding into nasal cavity : A case report

鼻腔内腫瘍として発症した浸潤性下垂体腺腫を経験したので細胞所見とともに報告する. 症例は64歳, 女性. 右鼻閉感と鼻出血が出現し, 耳鼻科にて鼻腔内腫瘍を指摘された. 頭部MRIで腫瘍は蝶形骨洞を主座とし, 眼窩, 上顎洞, 筋骨洞, 鼻腔への進展が認められた. トルコ鞍は腫瘍で置換されていた. 鼻腔からの生検で神経内分泌腫瘍と診断され, 当院脳神経外科にて経蝶形骨腫瘍摘出術が行われた. 捺印細胞像では腫瘍細胞は均一で平面的に配列していた. 細胞質は豊富でライトグリーンに淡染し, 核は円形でクロマチンは細顆粒状に増量していた. 組織像では充実性もしくは索状に配列し, perivascular pseudorosetteやmicrocystがみられた. 免疫組織化学にてcytoker-atin, chromogranin A, synaptophysinが陽性で, 下垂体前葉ホルモンは陰性であった. 電顕的には神経内分泌顆粒が認められた. 以上から下垂体腺腫null cell typeと診断した. 本腫瘍は頭蓋内の良性腫瘍だが, 時に周囲の骨を破壊して眼窩や鼻腔などの頭蓋外へ進展することがあり, 悪性腫瘍と誤認しないことが大切である.