Flow and image cytometric DNA analysis in rhabdomyosarcoma.

Rhabdomyosarcoma is the most common malignant soft-tissue tumor in childhood, with an overall 3-year disease-free survival of 73%. DNA content is known to correlate with prognosis and therapy response in many cancers. To determine the role of DNA content in rhabdomyosarcoma, 23 tumor samples were studied retrospectively: 18 primary tumors and 5 post-chemotherapy recurrences or specimens obtained at second-look surgeries. The DNA analysis was performed on disaggregated paraffin-embedded tissue nuclei by flow and image cytometry and correlated with the histology and clinical history. Of the primary tumors 4 were diploid, 4 polyploid, and 10 aneuploid (9 with a single aneuploid G0G1 peak and 1 multiploid) by flow cytometry. The concordance rate between flow and image cytometry was 19 of 23 (83%); one case did not have flow cytometry available. Most embryonal rhabdomyosarcomas were aneuploid (10 of 12; 83%), and they had a high incidence of recurrence in Stages III and IV (4 of 12; 33%). Although aneuploidy in pediatric cancers may predict a therapeutic response and good prognosis, this was not supported by our findings in rhabdomyosarcoma. The tumor DNA content correlated with the clinical stage but not with the patient's clinical course or tumor histopathological type. DNA content did not appear to be as important a prognostic tool as tumor stage.

Distribution of guaiacol peroxidase in human endometrium and endocervical epithelium during the menstrual cycle.

Guaiacol peroxidase (G-Px) was measured in extracts from five sections along the length of human uterus on different days of the menstrual cycle or after menopause. The lower uterine-endocervical region had a significantly higher G-Px content (expressed as enzyme units per g wet tissue) than the other sections, although in postmenopausal patients the G-Px activity was uniformly low in all sections of the uterine cavity. We observed no significant changes in G-Px levels during the menstrual cycle, except, possibly, a decrease around ovulation, which precluded a positive correlation between plasma estrogen levels and uterine G-Px content; such estrogen dependence of G-Px has been previously shown in the rat. In vitro, G-Px was inhibited by estriol and 17 beta-estradiol, marginally inhibited by estrone, and most notably inhibited by the catecholestrogens tested (2-hydroxy-17 beta-estradiol, 2-hydroxy-estriol, and 2-hydroxy-estrone), which were equipotent inhibitors; LH and FSH, progesterone, or cortisol had no effect on G-Px activity. We hypothesize that catecholestrogens are natural substrates and regulations of G-Px activity in the human uterus.

Myxoglobulosis of the appendix.

Myxoglobulosis is a rare morphologic variant of appendiceal mucocele characterized by intraluminal mucinous globules of the appendix. Most reported cases have presented clinically as an acute abdomen or as an incidental laparotomy or autopsy finding. We report a case of myxoglobulosis in a 32-year-old man who presented with an extra-appendiceal mass following a 10-year symptomatic course. Laparotomy disclosed a pericecal collection of opaque, white globules originating from a perforated appendix walled off by fibrous adhesions. The globules exhibited some histologic and staining properties at variance with those described in previous reports. These findings suggest that myxoglobulosis may be more heterogeneous pathogenetically than the distinctive gross appearance of the lesion would indicate.

Occult medullary thyroid carcinoma. Unusual histologic variant presenting with metastatic disease.

A 66-year-old man presented with an enlarged cervical lymph node, interpreted on fine-needle aspiration as squamous cell carcinoma. Histologic assessment of the excised mass demonstrated a mucin-positive glandular neoplasm that, by immunohistochemistry, was positive for carcinoembryonic antigen, calcitonin, and neuron-specific enolase. A subsequent total thyroidectomy revealed a grossly normal organ with a 2-mm microscopic focus of medullary carcinoma and foci of C-cell hyperplasia in the immediate vicinity of the tumor. No amyloid could be demonstrated in either lesion. The diagnostic difficulty encountered in this case is related to the presence of a rare morphologic variant (devoid of amyloid and forming mucin-positive glands) occurring as an occult primary but presenting as a metastasis. Although an occult primary in medullary carcinoma is recognized in familial cases, such a phenomenon is rare in sporadic cases.

Systemic rhabdomyosarcoma with diffuse bone marrow involvement. Case report of an unusual presentation.

Rhabdomyosarcoma presenting as a systemic disease is rare. This report concerns a 12-year-old girl who came to medical attention for what was thought to be a hematologic malignancy. Diffuse lytic bone lesions and large primitive cells in the bone marrow exhibiting erythrophagocytosis supported this diagnosis. During the course of the disease, a soft tissue mass in the region of the left ankle was removed and was a typical alveolar rhabdomyosarcoma. Retrospective review of the marrow, including electron microscopy, demonstrated that the primitive marrow cells were probably rhabdomyoblasts as well. The clinical course was a rapid downhill one in which lytic bone lesions and hypercalcemia were prominent. Although rhabdomyosarcoma eventually may disseminate, initial widespread disease without a clinically apparent primary can be a diagnostic dilemma. This clinical presentation, in combination with the recognized aggressiveness of the alveolar histologic subtype, identifies a rare subgroup of patients with rapidly fatal disease.

Breast cancer metastatic to the uterus. Clinical manifestations of a rare event.

Adenocarcinoma of the breast rarely metastasizes to the mucosal surfaces of the uterus. We present two patients with endometrial involvement, in one of whom it was the initial manifestation of her breast cancer. Two additional patients with cervical involvement had abnormal Papanicolaou smears and grossly normal cervices. One of these patients underwent a biopsy, the results of which confirmed metastatic adenocarcinoma. Three of the four patients had previously well-established metastatic disease. The presence of genital, especially mucosal, metastases is indicative of widespread disease and imminent demise. This occurred in one of the patients described here; however, another patient survived 30 months. Breast cancer is a chronic disease for which the metastatic behavior is exceptionally unconventional. Tissue acquired by endometrial curettage or colposcopy may require an awareness on the part of the pathologist to such a clinical circumstance.

Utility of specimen angiography in angiodysplasia of the colon.

This study reviews the utility of specimen angiography in identifying colonic lesions clinically thought to represent angiodysplasia. Four elderly patients presented with acute rectal bleeding. The diagnosis of angiodysplasia was made preoperatively in 3 patients by colonoscopy or angiography, or both. These specimens were injected with silicon rubber compound, xerographed, cleared with methyl salicylate, and examined with transillumination before histologic sampling. Although this technique was not used in the fourth case, fortuitous random sampling of the ascending colon revealed vascular changes indicative of angiodysplasia that correlated with a preoperative bleeding scan. Associated lesions in 1 patient were carcinoma of the colon and primary amyloidosis, the concurrence of which has not been described previously. With the injection technique the lesions of angiodysplasia appear grossly as spiderlike, dilated blood vessels. Microscopically, dilated veins, venules, and capillaries are found in the submucosa only or in the mucosa and submucosa. The importance of the postoperative injection is that it prevents the collapse of the blood vessels and enables the pathologist to identify the lesions grossly. As these lesions are usually small, this is important for proper sampling and histologic documentation.

Long-term survival and DNA ploidy in advanced epithelial ovarian cancer.

BACKGROUND AND OBJECTIVES: The relationship of the tumor DNA content to survival of patients with advanced epithelial cancer has not yet been clarified. A large amount of contradictory data exists in the literature. This study analyzes the putative relationship between ploidy and advanced ovarian carcinoma. METHODS: A retrospective analysis of tumor ploidy, DNA index, and the S-phase fraction from 35 patients with nonborderline epithelial ovarian carcinomas was determined by flow cytometry of paraffin-embedded tissue. All patients had FIGO stage III or IV disease. Those patients who survived > 5 years were assigned to Group A (10 patients). Group B consisted of 25 age-matched subjects who succumbed to their disease within 5 years of diagnosis. RESULTS: Group A had not reached a median overall survival with a median follow-up of 114 months (range 67-226), whereas Group B had a median overall survival of 17 months (range 1-48). Two of the patients in Group A and all of the patients in group B had died of the disease. The two groups were similar in age, histologic type, and treatment. In Group A, three patients had grade 1 tumors, in contrast to group B where all the patients had either grade 2 or 3 disease (P = 0.018). However, the distribution of aneuploidy was similar in both groups. Also, the DNA indices were similar: 1.40 +/- 0.42 in Group A, and 1.36 +/- 0.44 in Group B. The median S-phase fraction was 14% (range 3-23%) in Group A, and 15% (range 2-23%) in Group B. The grade and type of tumor were not related to the ploidy or the DNA index. There was no significant correlation between ploidy or the DNA index and survival. CONCLUSION: This study suggests that the DNA content of tumor as measured by flow cytometry is not a predictor of long-term survival in ovarian cancer patients with advanced disease.

Infantile sarcoma with intracytoplasmic filamentous inclusions: distinctive tumor of possible histiocytic origin.

This report describes four malignant tumors originating in infants, (one present at birth), for which a common origin is proposed. The common nature of these tumors was suggested by a remarkable similarity of histologic and ultrastructural features, including the presence of intracellular filamentous aggregates, as well as a shared aggressive clinical course consistent with sarcomatous origin. Two of these neoplasms arose within the kidney and were classified as "rhabdoid" sarcomas, according to the NWTS nomenclature. However, cells from these neoplasms could not be identified as muscular in origin. In culture, these cells demonstrated adherence to substratum, ability to phagocytose particles, and cell surface complement receptors. In addition, the renal tumors contained definite tumor cells positive for muramidase; the liver primary tumor contained only a limited number of such cells, which could not be interpreted as neoplastic. These findings suggest that among the "round-cell sarcomas" of infants and young children, a distinct, highly malignant form may be identified on clinical and morphologic grounds. The possibility that the tumor cells may be linked to the mononuclear phagocyte system was suggested, but not proved, and deserves further study.