Latifa Ghandur-Mnaymneh

Dysplasia of Nonmetaplastic Gastric Mucosa: A Proposal for its Classification and its Possible Relationship to Diffuse-Type Gastric Carcinoma

In a review of 192 gastric resections, histological changes believed to represent dysplasia of nonmetaplastic gastric epithelium were observed. This paper presents a proposal for their classification. The main feature of this dysplasia is replacement of the differentiated cells lining the glands by undifferentiated cells with varying degrees of cytological abnormalities and cellular pleomorphism, but with absence of architectural glandular derangement. The classification is justified by cytokinetic and histologic observations in experimental gastric carcinogenesis and early human gastric carcinoma. The severity of the changes is graded, first, by the extent of involvement of the gland (crypt) as measured from the proliferative zone (PZ), and, second, by the degree of cytological abnormality. It utilizes a modification of the terminology of Riddell et al. (45) for dysplasia in inflammatory bowel disease wherein the term “dysplasia” denotes intraepithelial neoplasia. The changes are classified into (a) negative for dysplasia, (b) atypical, i.e., indefinite for dysplasia, and (c) positive for dysplasia. Changes negative for dysplasia are considered regenerative and consist of enlargement and vesicular transformation of the nucleus in the cells of the PZ and adjacent part of the crypt. Atypical changes consist of equivocal lesions difficult to classify as definitely regenerative or definitely dysplastic, and are hence called indefinite for dysplasia. They consist of loss of cytoplasmic differentiation of the cells lining the glands (i.e., mucus production and parietal and chief cell differentiation) with increased nuclear-cyto-plasmic ratio and moderate cytological atypicality. Based on the extent of gland involvement, the group with atypical mucosa is subdivided into two categories—atypical, probably negative for dysplasia (AtN) and atypical, probably positive for dysplasia (AtP). Mucosa exhibiting unequivocal cytological features of neoplasia with cellular and nuclear pleomorphism is classified as positive for dysplasia (D). This is subdivided into low-grade and high-grade dysplasia, the latter representing carcinoma in situ. Glandular architecture remains undisturbed in all stages and the cells remain cuboidal, without transformation into intestinal-type cells. This type of dysplasia was found in a significantly higher number of diffuse-type carcinomas than in intestinal-type carcinomas. The previously well-recognized adenomatous or metaplastic dysplasia was significantly more prevalent in intestinal-type carcinoma than in diffuse-type. We believe that this non-metaplastic dysplasia represents a second pathway in the genesis of gastric carcinoma, possibly the diffuse type, and would thus serve as an additional indicator of individuals at risk for gastric cancer. Our findings suggest that the PZ is the site of origin of this dysplasia.

Massive distal femoral osteoarticular allografts after resection of bone tumors.

Records were reviewed for 96 patients who received distal femoral osteoarticular allografts to reconstruct femurs after wide resections of benign and malignant bone tumors. Thirteen of these were excluded from the study because of death or local recurrence. The mortality rate for all patients was 11%; for those with osteosarcomas it was 27%. The local recurrence rate was 3%. Eighty-three patients were subjected to further analysis. Their complications included fractures (14%), nonunions (12%), arthritis (10%), instability (7%), infections (6%), and resorption (6%). There was a significant difference in nonunion and infection rates between patients who received chemotherapy and those who did not. In the chemotherapy group, the infection rate was 13% versus 2% in the non-chemotherapy group. Nonunion rates were 23% versus 6% respectively. The differences in all other complication rates were not statistically significant. In patients not receiving chemotherapy (n = 53), final results were good or excellent in 70%, fair in 26%, and poor in 4%. In patients receiving chemotherapy (n = 30), final results were good or excellent in 53%, fair in 37%, and poor in 10%.

Adrenal Cysts: Pathogenesis and Histological Identification With A Report Of 6 Cases

Because of their rarity cysts of the adrenal gland are often misinterpreted and misdiagnosed. Six cases of surgically removed adrenal cysts are presented, including 3 endothelial cysts, 2 epithelial retention cysts and 1 pseudocyst. Evidence is presented that epithelial retention cysts could and do develop in the human adrenal cortex and are not theoretically impossible as propagated in the literature. We also emphasize the importance of evaluating the surrounding fibrous and adrenal tissue in the proper identification of these cysts, a point not sufficiently stressed previously.

Are the Mast Cells Antigen Presenting Cells

Mast cells have an important role in allergic reactions secreting histamine and other mediators of immediate hypersensitivity. In the present study we evaluated major histocompatibility complex (MHC) class II antigen expression in mast cells and their possible role in antigen presentation. In rats, 10% of mast cells isolated from the pleural cavity expressed MHC class II antigen; after incubation with gamma interferon (INF) 80% of the cells were positive. These findings suggest that mast cells, in addition to their secretory function in allergic reactions, may also function as antigen presenting cells.

The use of touch preparations (tissue imprints) in the rapid intraoperative diagnosis of metastatic lymph node disease in cancer staging procedures

Three hundred lymph nodes submitted for the intraoperative diagnosis of metastatic disease were studied by use of touch preparations (TP), i.e., tissue imprints, using the modification previously described by the senior author, the conventional frozen section (FS), and permanent sections. There were 215 negative and 85 positive lymph nodes. Compared with permanent sections, TP gave an accuracy of 99% and the FS an accuracy of 98.7%. In view of this reliability and the significant saving of valuable intraoperative time provided by the TP technique, we recommend that TP be used instead of the FS in cancer staging procedures where many lymph nodes are submitted for immediate intraoperative examination for the determination of extent of surgery.

Multinodular oncocytoma of the parotid gland: A benign lesion simulating malignancy

Oncocytomas of the salivary glands are rare. Occasionally, they are multinodular, which imparts a malignant appearance. Only eight such cases have been reported, and an additional case is reported herein. Dense cytoplasmic acidophilia is an important clue in the identification of the lesion. When this feature is lacking, the lesion may be mistaken for the more aggressive acinic cell tumor. Histochemical strains are not as useful as generally believed. Electron miscroscopy confirms the diagnosis by demonstrating an abundance of mitochondria. The presence of oncocytic cellular buddings from the intercalated ducts and ductules surrounding the tumor and the lobular oncocytic transformation were important aids in the recognition of multinodular oncocytoma.

The incidence and mechanism of transphyseal spread of osteosarcoma of long bones.

Although the physeal cartilage is considered resistant to invasion by metaphyseal osteosarcoma, no objective clinical proof exists to support this view. Fourteen cases of osteosarcoma of long bones in patients ranging in age from ten to 19 years with open physes were reviewed to determine the incidence of transphyseal spread. The physeal cartilage was not crossed in only two cases. In the remaining 12 cases the tumor crossed the cartilaginous plate partially or completely, remaining in the epiphysis in seven and crossing the articular cartilage and involving the joint in five. Histologic sections showed that increased vascularity occurs initially, followed by osteoclastic and chondroclastic activity at the physeal plate with subsequent tumor tissue invasion. The incidence of transphyseal spread in the three published series (total of 64 cases, including the present 14 cases) is 81.2%. This is contrary to the often published unsupported statements of others. Transphyseal spread of osteosarcoma is the rule rather than the exception.

Characteristics and Clinical Correlates of a Novel Thyroid-Stimulating Autoantibody

We reported a patient who gave birth to 3 children with transient neonatal hypothyroidism. She had 3 different antibodies (Ab) to the thyrotropin receptor (TSHR) in her serum, viz., TSH binding-inhibiting (TBIAb), thyroid-stimulating (TSAb) and an additional stimulating Ab (SAb). The SAb differed from TSAb in that its in vitro stimulating effect in human thyroid and FRTL5 cells was not inhibited by TBIAb [similar data now obtained with Chinese hamster ovary (CHO) cells transfected with cloned human TSHR]. Because of symptomatic goiter enlargement the patient underwent subtotal thyroidectomy. About 50% of the gland was infiltrated with lymphocytes; thyroid follicles had columnar epithelium, despite suppression of TSH by thyroxine and the presence of the potent TBIAb. Fifteen months later, when all 3 Ab showed a decline of approximately 3 fold, she gave birth to hypothyroid twins. These data support the following conclusions: 1) thyroidectomy and immunosuppression of pregnancy do not prevent neonatal thyroid disease if TSHR Ab (TRAb) are of high titer; 2) the thyroid is not a major site of TRAb production; 3) SAb is a thyroid stimulator, distinct from TSAb in that it does not share binding epitopes on the TSHR with either TSH or TBIAb; 4) SAb was the probable cause of thyroid growth in this patient.

The Effect of Thyroxine on Spontaneous Thyroiditis in BB/W Rats

The effect of T4 on the incidence of lymphocytic thyroiditis and on titers of antibodies to thyroglobulin and thyroid microsomal antigen was studied in BB/W rats that are prone to develop spontaneously autoimmune thyroiditis and diabetes. Thirty-three animals were separated in two groups. Rats in one group had 1 mg T4 per liter of drinking water, and the other group was given no T4. After 3-4 months of therapy the T4-treated group had a reduced production of antibody to thyroglobulin (p less than 0.05) and to microsomal antigen (p less than 0.005) and a significantly lower frequency of lymphocytic thyroiditis (p less than 0.05). Our data are consistent with previous findings in experimentally induced thyroiditis in rats and suggest that T4 has an immunosuppressive effect.

Lobular carcinoma of the breast metastatic to bone with unusual clinical, radiologic, and pathologic features mimicking osteopoikilosis

A 55‐year‐old woman who underwent a right radical mastectomy for infiltrating lobular carcinoma was found to have multiple diffuse osteoblastic bone lesions. Since she was asymptomatic, had no elevation of alkaline phosphatase, and the lesions did not take up technetium pyrophosphate on bone scan, she was thought to have osteopoikilosis. An iliac bone biopsy was performed that showed greatly thickened bony trabeculae with diffuse delicate marrow fibrosis entrapping easily overlooked short strands of small malignant cells. The histologic picture also closely resembled osteopoikilosis. Although infiltrating lobular carcinoma has been recognized as separate from ductal carcinoma in the primary site, its recognition in metastatic foci is still vague. Attention is drawn to its histologic appearance in skeletal metastases so that such lesions will be more recognizable in the future.