Motohiko Aiba

Histopathological diagnosis and prognostic factors in adrenocortical carcinoma.

A great majority of adrenocortical tumors are benign, and many adrenocortical carcinomas (ACC) are obviously malignant at presentation. The histopathological diagnosis of ACC is occasionally difficult, particularly with stage I and stage II disease. The prognosis of ACC is generally poor. Surgery is the major treatment, with chemotherapy and radio-therapy being applicable to only restricted patients. The Weiss criteria are useful in diagnosing the common adult type of ACC. Histopathological prognostic factors of ACC have not been fully established because of the rarity of the disease.In this article, we first describe the current histopathological diagnostic and prognostic factors of ACC, highlighting the special types of ACC to which Weiss’s criteria are not fully applicable. These special type tumors include pediatric adrenocortical tumors, oncocytomas, and aldosterone-producing tumors of pure zona glomerulosa type. Then we present three cases with unusual small adrenocortical tumors. One patient had an unequivocal ACC showing metastatic disease. One had a histologically defined ACC with no metastasis or macroscopic invasion. The third was a pediatric patient with a tumor showing a nodule-in-nodule pattern with insulin-like growth factor II expression.

Alteration of subcapsular adrenocortical zonation in humans with aging: the progenitor zone predominates over the previously well-developed zona glomerulosa after 40 years of age.

Few studies have examined functional adrenal zonation throughout human life. Adrenals from 61 surgical/autopsy patients from 1 day old to 92 years old who had no clinical endocrinological/mineralocorticoid abnormalities were assessed for immunohistochemically defined adrenal zonation. The zona glomerulosa (zG) was well developed in all 11 patients ranging in age from newborn to the 30s. After 40 years of age, however, the zG occupied less than one-quarter of the adrenal circumference, suggestive of zG involution. The other subcapsular areas were occupied by the progenitor zone (zP), which expressed neither cytochrome P450aldo nor P45011β but 3β-hydroxysteroid dehydrogenase and P450scc, although some autopsy cases had adrenals with zG zonation because of secondary aldosteronism, and others who had experienced severe stresses showed subcapsular zona fasciculata (zF). In conclusion, the adrenal cortex consists of homogeneous zG-topped columns from birth to adolescence. Subsequently, in the fifth decade of life, the cortex is reconstituted by integration of three types of cortical columns: scattered zG-topped columns and zonal zP-topped columns, the latter having the ability for bidirectional differentiation into either zG-topped columns or zF-topped columns, according to secondary aldosteronism or the presence of severe stresses. Such adrenocortical remodeling is ascribed to high-sodium/low-potassium diets.

A Case of Benign Schwannoma of the Transverse Colon with Granulation Tissue

Schwannomas occurring in the gastrointestinal tract are rare, and among them, schwannomas of the large intestine are extremely rare. In this paper, we report a case of a macroscopically atypical schwannoma of the transverse colon. The case is a female aged 67. Stool occult blood test was positive, and colonoscopy revealed a protruded lesion resembling a type 1 carcinoma measuring 4 cm with a reddish and uneven surface on the transverse colon. The surface was smooth and lobulated in observation with indigo carmine spray, and granulation tissue was revealed by biopsies. CT of the abdomen showed an irregular mass, and clinical examinations could not rule out malignancy. Therefore, partial transverse colectomy with peripheral lymph node dissection was performed. Histologically, proliferation of spindle cells was observed originating from the muscularis propria, and most of the upper part of the lesion was replaced by granulation tissue. In immunohistochemical staining, S-100 protein and NSE were positive while KIT, CD34, desmin and smooth muscle actin were negative, and the tumor was therefore diagnosed to be a schwannoma. In addition, since the MIB-1 labeling index was low and virtually no mitosis was observed, it was diagnosed as benign tumor.

Adrenal cortical diseases: International case conference

Six pathologists from Japan and the United Kingdom evaluated four different cases of adrenocortical disorders independently. These adrenocortical disorders included an adrenal tumor in a 45-yr-old female without any endocrine abnormalities, bilateral adrenocortical lesions in a 55-yr-old female with Cushing syndrome, an adrenocortical mass in a 44-yr-old man with hypertension, and an adrenocortical lesion in a 62-yr-old female with chronic hypertension for 30 yr. In this article, we provide a clinical summary, macroscopic and histologic findings, and histologic diagnosis of these four adrenocortical cases.

Squamous cell carcinoma of the soft palate associated with autoantibodies to desmoglein 1 and 3

The desmogleins are a family of cadherins cell-cell adhesion molecules consisting of proteins DSG1, DSG2, DSG3, and DSG4. They play a role in the formation of desmosomes, which form the major types of intercellular adhesive junctions. DSGs are currently thought to be involved in autoimmune diseases, infectious diseases, and inherited diseases. Patients with pemphigus, an autoimmune blistering disease of the skin and mucous membranes, carry IgG autoantibodies directed against DSG1 and DSG3 [1]. Pemphigus vulgaris antigen is also considered a tissue-specific type of desmoglein [1].

Establishment and characterization of a novel VEGF-producing HHV-8-unrelated PEL-like lymphoma cell line, OGU1.

Primary effusion lymphoma (PEL) is a rare B‐cell lymphoma subtype that is characterized by lymphomatous effusion without the presence of masses, and it typically occurs in human immunodeficiency virus (HIV)‐infected individuals. Lymphoma cells are universally positive for human herpesvirus 8 (HHV‐8). Recently, a cavity‐based effusion lymphoma that is similar to PEL without HHV‐8 infection, called HHV‐8‐unrelated PEL‐like lymphoma, has been reported in non‐HIV‐infected individuals. However, the pathophysiology of this lymphoma is largely undefined. We established a novel B‐cell line OGU1 derived from a patient with HHV‐8‐unrelated PEL‐like lymphoma. Notably, OGU1 cells produced vascular endothelial growth factor (VEGF) and expressed VEGF receptor 1, whose inhibitors retarded cell growth. Because VEGF acts as a vascular permeability and growth factor, it could play a role, at least in part, in the pathogenesis of this unique lymphoma. Thus, the OGU1 cell line is useful for the investigation of HHV‐8‐unrelated PEL‐like lymphoma.

Peristomal Pagetoid Spread of Urothelial Carcinoma of the Ureter

Patients with ostomy including urinary stoma often develop peristomal complications, especially skin damage. The patient in this case was a 69-year old female with a history of urothelial carcinoma of the bladder and left ureter who underwent transurethral resection of a bladder tumor, nephroureterectomy and cystectomy combined with ureterocutaneostomy. Later, she had recurrence of urothelial carcinoma in the remaining ureter that spread to the peristomal epidermis, with a skin appearance resembling Paget’s disease. We report this case based on its clinical significance since we believe it is the first description of this condition in the literature.