Bacillary epithelioid angiomatosis involving the liver, spleen, and skin in an AIDS patient with concurrent Kaposi's sarcoma.

The simultaneous findings of bacillary epithelioid angiomatosis and Kaposi's sarcoma of the skin with visceral hepatosplenic bacillary epithelioid angiomatosis is reported in a patient with acquired immune deficiency syndrome. Liver biopsy showed periportal peliotic spindle cell foci that initially were misinterpreted as Kaposi's sarcoma. After antibiotic therapy induced rapid clinical improvement, repeated liver biopsy showed resolution of the previously noted lesions. Although the violaceous skin lesions all appeared similar clinically, some resolved completely and some progressed. One of the latter was biopsied and had the histologic features of Kaposi's sarcoma. The differential diagnosis is discussed.

The spectrum of clinical and laboratory findings resulting from human herpesvirus-6 (HHV-6) in patients with mononucleosis-like illnesses not resulting from Epstein-Barr virus or cytomegalovirus.

Recently, the morphologic, immunologic, and molecular makeup of a new virus designated human herpesvirus-6 (HHV-6) has been described. Because cell cultures of HHV-6-infected mononuclear cells showed prominent lymphocytic changes, it could be anticipated that mononucleosis-like illnesses or lymphoproliferative disorders would turn out to be manifestations of active HHV-6 infection. In the present study, blood samples from 27 patients previously categorized as having non-Epstein-Barr virus (non-EBV)/noncytomegalovirus (non-CMV) heterophil-negative mononucleosis-like illnesses were tested for IgM and IgG antibodies to HHV-6. Eight of these patients (30%) had serologic evidence of active HHV-6 infection. The clinical spectrum includes a short-lived febrile illness, mild cervical lymphadenopathy, laboratory data suggestive of active viral hepatitis in two patients, and a prolonged febrile illness in a single patient with previously documented positive anti-HIV serology. The viral studies revealed the presence of fourfold HHV-6-specific IgG titer increases by immunofluorescent assay (IFA) in seven serially studied cases and positive IgM serology on one or more samples tested by IFA or enzyme-linked immunosorbent assay (ELISA) in all eight cases. The authors could not determine whether the illnesses represented primary HHV-6 infections in susceptible individuals or reactivation of latent virus. HHV-6 serologic studies may be indicated in patients with mononucleosis-like illnesses with atypical lymphocytosis when EBV and CMV test results are nondiagnostic.

Fine-needle aspiration of lymph nodes in patients with acute infectious mononucleosis.

We studied lymph node fine-needle aspirations from 10 patients with primary Epstein-Barr virus (EBV) infections (infectious mononucleosis). There were five males and five females, aged 15-54 yr. The diagnoses were confirmed by blood morphology and heterophil antibody (HA) and EBV-specific serologic studies. Nine patients were HA-positive, nine were viral capsid antigen (VCA)-IgM-positive, and all 10 were VCA-IgG-positive and anti-EBV nuclear antigen (EBNA)-negative. Five patients were referred for fine-needle aspiration biopsies for clinically suspected malignant lymphoma (ML). Four of these patients had been tested for HA prior to fine-needle aspiration, with negative results in three cases. The heterophil-positive patient was referred for fine-needle aspiration due to very impressive unilateral cervical adenopathy. Cytologically, all cases showed atypia consisting of greater numbers of large immunoblastic lymphocytes than are usually seen in the reactive lymph node. Two cases were cytologically suspicious for malignant lymphoma but included a considerable background of polymorphic immunoblasts. We suggest that polymorphic immunoblastic proliferations in lymph node cytology are suggestive of infectious mononucleosis. Since several reactive and neoplastic processes mimic this pattern, cases not followed by both confirmatory serologic studies and resolution of adenopathy should be pursued by excisional lymph node biopsy.

Severe thrombocytopenia in Epstein-Barr virus-induced mononucleosis.

Severe thrombocytopenia is a rare complication of Epstein-Barr virus-induced infectious mononucleosis. We evaluated the clinical and laboratory data from seven patients seen between 1976 and 1985 whose lowest platelet counts varied from 3 to 25 x 10(9) per liter. Five of the seven patients were initially thought to have either acute leukemia or idiopathic thrombocytopenic purpura; eventually, however, primary Epstein-Barr virus infections were confirmed in all patients. Two of six patients tested had antiplatelet antibodies during the acute phase of their illnesses. Eight additional patients with acute disease who had only mild thrombocytopenia (94 to 144 x 10(9) per liter) were also tested for platelet antibodies with negative results. Steroid therapy was administered to three patients and platelet transfusions to one. All seven patients recovered with no serious hemorrhagic sequelae.

Heterophil-negative mononucleosis-like illnesses with atypical lymphocytosis in patients undergoing seroconversions to the human immunodeficiency virus.

The authors present data from four patients with acute heterophil-negative mononucleosis-like illnesses who were initially thought to have primary Epstein-Barr virus (EBV) infections but eventually were shown to be seroconverting to the human immunodeficiency virus (HIV). Widespread lymphadenopathy and blood smears indistinguishable from those typically encountered in the acute phase of infectious mononucleosis were present in all cases. There were also varying combinations of fever, sore throat, and malaise, as well as mild abnormalities of hepatic function and elevated cold agglutinins (anti-I). Anti-HIV was detected by both enzyme-linked immunosorbent assay and Western blot techniques in all cases, with increasing titers noted in two of three serially studied cases. In one patient, a dual infection with the hepatitis B virus was also documented. Diagnostic possibilities in patients with acute mononucleosis-like illnesses dominated by prominent lymphadenopathy should include primary seroconversions to HIV.

Platelet utilization in a university hospital.

Two hundred forty-three patients received 22,717 U of platelets in our hospital during a three-month period. Those with hematologic diseases accounted for 43% of the patients but used 86% of the platelets. Sixty-eight percent of the transfusions were given to prevent bleeding and 32% were given to treat active bleeding. Ninety-two percent of therapeutic transfusions but only 22% of prophylactic transfusions met guidelines established by the Transfusion Therapeutics Committee of the University of Minnesota Hospital and Clinics, Minneapolis. However, 78% of prophylactic platelet transfusions that did not meet the guidelines involved patients with at least one clinical factor that their physicians believed placed them at an increased risk of bleeding. Following this analysis, the guidelines were modified and applied prospectively to requests for platelets. This resulted in a 14% decrease in the number of platelet units used during the following year. We conclude that published recommendations for platelet transfusions do not reflect the complex nature of many patients' conditions and that the use of guidelines developed by the medical staff can alter the use of platelet transfusions.

Alpha-fetoprotein localization in pure ovarian teratoma. An immunohistochemical study of 12 cases.

Twelve cases of pure ovarian teratoma were studied by immunohistochemical methods to determine the incidence and localization of alpha-fetoprotein (AFP) production. There were six mature teratomas (grade 0) and six immature ones (grades 1-3). Three tumors (grades 1, 3, and 3 and stages III, I, and III, respectively) had isolated foci of AFP immunoreactivity in yolk-sac-like vesicles, intestinal-type epithelium, or tissue resembling liver, whereas the other nine tumors had no AFP-positive components. The former three patients had preoperative serum AFP determinations; the values were elevated in two of them, and in both instances the oncofetoantigen became undetectable one month after oophorectomy. Both patients are alive and well 15 and 25 months later; the third patient with a normal serum AFP before surgery and a positively stained tumor died of recurrent disease. The authors' findings indicate that the production of AFP in pure ovarian teratomas recapitulates its pattern of synthesis during ontogeny. Furthermore, it is suggested that a preoperative elevation of serum AFP in a pure ovarian teratoma does not seem to correlate with stage or grade, beyond minimizing the possibility that the tumor is grade 0, or mature.

Selected aspects of acute and chronic infectious mononucleosis and mononucleosis-like illnesses for the practicing allergist.

The diagnosis of EBV-IM or a heterophil-negative mononucleosis-like syndrome is best approached by combining morphologic and serologic data. The minimal hematologic criteria should always be searched for before accepting a case as IM or an IM-like illness. If minimal morphologic data are not rigidly adhered to, the number of heterophil-negative cases included under the umbrella of IM or an IM-like illness will swell and include a variety of other illnesses where early diagnosis may be important for treatment purposes. When EBV studies are indicated, the entire profile (VCA-IgM, VCA-IgG, and anti-EBNA) should be performed. Anti-VCA-IgG titers alone, for example, are of very limited usefulness unless they are negative (less than 1:10), in which case the diagnosis of EBV-IM is excluded. The main problems connected with the diagnosis of the CMS center about the nonspecificity of both clinical and EBV serologic data. Thus, a significant effort must be made to rule out underlying disease, especially those chronic illnesses with immunosuppressive effects that are capable of reactivating the EBV latency state and producing EBV serology similar to that seen in CMS. Other dilemmas relate to diagnostic cut-off levels for particular EBV-related tests, including antibodies to EA and the relative unavailability of several tests for detection of subtle immunodeficiency or T-cell dysfunction in individual patients with suspected CMS. Future efforts will be directed to the diagnostic usefulness of antibody responses to well-defined recombinant fragments of the EBV genome (ie, anti-EBNA1 vs. -EBNA2 titers).

Gm allotyping to determine the origin of red cell antibodies in recipients of solid organ transplants.

Alloantibodies of A and B specificity were detected in the serum and on the red cells of 4 non-0 recipients of group 0 solid organ transplants. The antibodies were assumed to be produced by 'passenger' lymphocytes introduced at the time of transplant. Gm allotyping of donor serums, recipient serums and the unexpected antibodies was done. Gm typing was informative in 1 case, when the anti-A1 found in the serum of a liver transplant recipient was shown to be of phenotype Gm(fb) and the Gm phenotype of the recipient to be Gm(axg). Gm allotyping was not informative in the other 3 cases.

Minimal deviation adenocarcinoma of the uterine cervix ("adenoma malignum"). An immunohistochemical comparison with microglandular endocervical hyperplasia and conventional endocervical adenocarcinoma.

In an effort to obtain objective information that would be useful in separating minimal deviation adenocarcinoma (MDA) or "adenoma malignum" of the endocervix from benign endocervical glandular proliferations, four cases of MDA were studied immunocytochemically, and compared with seven cases of microglandular endocervical hyperplasia (MEH) and six cases of conventional endocervical adenocarcinoma (ACA). Monoclonal antibodies to carcinoembryonic antigen (CEA) and blood group isoantigens A, B, and H (BGI) were used in these analyses. All MDA and ACA were CEA-positive, whereas none of the cases of MEH stained for the presence of this substance. Six of seven examples of MEH expressed appropriate BGI; the remaining case failed to stain for blood group substances. In contrast, six of ten cases of malignant endocervical glandular tumors manifested "inappropriate" expression of BGI, based on the patients' known blood types. These data suggest that immunostains for CEA may be helpful in the diagnostic separation of MDA and MEH. The close biochemical similarity between CEA and BGI is postulated as an explanation for "inappropriate" expression of blood group antigens by malignant endocervical lesions.

Anaplastic thyroid carcinoma. A study of 70 cases.

Seventy cases of anaplastic thyroid carcinomas studied at the Universities of Florence (Italy) and Minnesota are presented. Three morphologic patterns were seen: spindle, giant cell, and squamoid, sometimes in combination. Ultrastructurally, evidence of epithelial differentiation was seen in most but not all cases studied. Immunohistochemically, a stain for cytokeratin using a monoclonal antibody was found the most useful adjunct to diagnosis. Unexpected positivity for carcinoembryonic antigen (CEA) was found in several squamoid tumors. The alleged frequent positivity of this tumor type for thyroglobulin and calcitonin was not confirmed. A third of the tumors were associated with a better differentiated component, of which, presumably, they represented a dedifferentiation. The extremely aggressive behavior of anaplastic thyroid carcinomas was confirmed amply in this series: all of the patients in whom follow-up information was available died of their tumor. Small cell tumors should not be included into the anaplastic category, since they invariably belong to other groups, i.e., malignant lymphoma, medullary carcinoma, and poorly differentiated ("insular") carcinoma.

Therapeutic cytapheresis using the Fenwal CS-3000 blood cell separator.

20 patients, 16 with acute or chronic leukemia and 4 with thrombocytosis, underwent 47 therapeutic cytapheresis procedures using the Fenwal CS-3000 cell separator. 16 of the 20 patients had acute clinical signs or symptoms secondary to high circulating cell counts; 14 showed symptomatic improvement following cytapheresis. An average of 2.0 whole blood volumes was processed per procedure. A mean white cell reduction of 64% and a mean platelet reduction of 53% were obtained per procedure on patients with leukemia and thrombocytosis, respectively. Hemoglobin levels decreased an average of 1.3 g/dl. Therapeutic cytapheresis procedures in which more than 1.5 blood volumes were processed did not result in significant additional cytoreduction.

Solid ovarian teratomas: an immunocytochemical study of thirteen cases with clinicopathologic correlation.

The modified histologic grading system for solid ovarian teratomas used by Norris et al. which attempts to quantitate the presence and amount of primitive neuroepithelium, is in our opinion, an improvement over the original system. In our experience, however, some difficulties in its application remain. Grade 0 and 1 tumors were easily identified, but there was considerable confusion in attempting to separate grade 2 tumors in which neuroepithelium does not exceed three low-power microscopic fields in any one slide from grade 3 tumors in which neuroepithelium occupies four or more low-power fields. The difficulty arose in deciding whether the amount of neuroepithelium required to qualify as "occupying" a low-power field was sufficient if a single focus was present, or if the entire microscopic field should contain neuroepithelium. In the former case, four small foci of primitive neural tissue present in separate locations in a single slide would qualify for diagnosis as a grade 3 tumor, whereas if the same amount of tissue was found close together (i.e., within the space of a single low-power field), it might be read as a grade 1 tumor. This system is also potentially dependent on a fortuitous sampling technique, since a grade 3 tumor could be diagnosed as a lesser grade if a particular section in which four low-power fields containing neuroepithelium is not chosen for microscopic examination. One of the most important steps in attempting to resolve some of the conflicts surrounding the correlation of tumor histology with natural history in solid ovarian teratomas is to assure adequate sampling of the tumor. Norris et al. suggest that one block per centimeter of the maximum diameter of the tumor should be evaluated, others stress the importance of directing sampling toward areas of hemorrhage or necrosis, in an attempt to disclose immature foci. Because of these potential problems, we suggest as a possible alternative using the estimated percentage of neuroepithelial tissue present in all the tissue examined microscopically as a basis for determining the histologic grade. In our small series, it appears that tumors without neuroepithelium would be equivalent to a grade 0, tumors with up to 10 percent neuroepithelium would be graded 1, those with approximately one-third neuroepithelium would be grade 2 tumors and those with approximately one-half or greater of their tissue as a neuroepithelium would be grade 3 tumors.(ABSTRACT TRUNCATED AT 400 WORDS)

Squamous cell carcinoma with sarcoma-like stroma of the female genital tract. Clinicopathologic study of four cases.

Four cases of squamous cell carcinoma with sarcoma-like stroma located in the vulva (1), vagina (2) and cervix (1) of postmenopausal women are presented. The gross and microscopic features are very similar to those of similarly named tumors occurring in the upper respiratory and digestive tract and in the skin. Light microscopic, electron microscopic, and immunohistochemical examination provided convincing evidence that these tumors are composed solely of squamous cell carcinoma, which has undergone a spindle cell sarcoma-like transformation in the deeper portions. Follow-up revealed an aggressive clinical course in three of the four patients, who died of their tumor between 2 and 45 months after presentation. At the time of death, two of the patients had widespread metastases and the other had massive local recurrence.

Aggressive angiomyxoma of the female pelvis and perineum. Report of nine cases of a distinctive type of gynecologic soft-tissue neoplasm.

Nine case of a distinctive soft tissue tumor of the female pelvis and perineum are described. They were characterized by their occurrence in young women (ages 21-38), large size (up to 60 X 20 cm), locally infiltrative nature, and grossly gelatinous appearance. The initial clinical impression was usually that of a Bartholin gland cyst. The microscopic appearance was that of spindle or stellate cells widely separated by a loose myxoid stroma focally rich in collagen fibrils, a prominent vascular component, including many large thick-walled vessels without an arborizing pattern, and foci of proliferating glandular elements in two cases. Mitotic activity was exceedingly low. Ultrastructural study of the spindle cells showed features consistent with myofibroblastic differentiation. Four patients developed large local recurrences; one tumor recurred twice, 14 and 15 years after initial excision. No distant metastases have been documented to date, and all patients are alive and well. The differential diagnosis of this unusual tumor includes myxoma, myxoid liposarcoma, sarcoma botryoides, myxoid variant of malignant fibrous histiocytoma, nerve sheath myxoma, and other soft tissue tumors with secondary myxoid changes. We have chosen the term "aggressive angiomyxoma" for this neoplasm to emphasize the neoplastic nature of the blood vessels and its locally infiltrative and recurrent nature.

Further delineation of the C (trigonocephaly) syndrome.

This communication brings the number of recognized cases of the C (trigonocephaly) syndrome to 11. The pattern of findings includes an anomaly of the anterior cranium and frontal cortex (trigonocephaly), the root of the nose (broad nasal bridge, epicanthus, and short nose), and palate (thick anterior alveolar ridges); abnormalities of the limbs (polysyndactyly, bridged palmar creases, short limbs, and joint dislocations and/or contractures); visceral defects (congenital heart defects, cryptorchidism, and abnormal lobulations of the lungs and kidneys). Auricular, mandibular, skin, and genital abnormalities also occur. Consistent neurological findings are hypotonia, strabismus, and psychomotor retardation; seizures have been reported. Normal chromosomes, normal parents with multiple affected offspring, equal sex ratio of affected individuals, and consanguineous matings all support autosomal recessive inheritance of the C syndrome. In autopsied cases, there has been a suggestion of defective central nervous system myelination. About 1/2 of the case have died within the first year. All survivors have severe to profound mental retardation except for one child who has moderate retardation.