Charles A. Santos-Buch

BACKGROUND: Subsequent to the publication of a report in 1984 entitled "Poorly Differentiated ("Insular") Carcinoma: A Reinterpretation of Langhans "wuchernde Struma," poorly differentiated insular thyroid carcinoma (PDITC) has become recognized as a distinct thyroid neoplasm. It is classified morphologically and biologically as an intermediate entity between well-differentiated (papillary and follicular) and undifferentiated (anaplastic) thyroid carcinomas. Only a few publications have addressed the findings with fine needle aspiration biopsy (FNAB). CASE: A 67-year-old female presented for evaluation of a massively enlarged thyroid gland. Fine needle aspiration biopsy of the thyroid with a 22-gauge needle showed many large, multilayered, round to oval nests of tumor cells, 0.2-0.4 mm in diameter. Rosettelike configurations of 8-15 cells, 0.025-0.050 mm in diameter, were also observed. Nests of neoplastic cells in the histologic sections were virtually identical to those in the fine needle aspiration biopsy specimens. When the patient developed metastatic cervical adenopathy one year later, a microfollicular pattern was seen on both the FNAB and histologic sections. CONCLUSION: When nests of tumor cells, 0.2-0.4 mm in diameter, are identified in a thyroid FNAB specimen, PDITC should be included in the differential diagnosis. A microfollicular pattern in a metastatic lymph node does not exclude the possibility that the primary tumor is a PDITC.

Experiments that consisted of incubation of Trypanosoma cruzi-sensitized lymphocytes derived from chronically infected rabbits and from rabbits repeatedly immunized with a small particle or membrane fraction derived from homogenates of T. cruzi forms, showed destruction of allogeneic, parasitized and nonparasitized heart cells in vitro. Mononuclear cells collected from peripheral blood were incubated for 1 h at 37 degrees C to isolate the lymphocytes. Following incubation, over 99% of the cells in the supernate were lymphocytes, which were utilized in these experiments. At the start of these experiments, 70-80% of the sensitized lymphocytes were unattached, small and round, with sparse filipodia. In the ensuing hours, marked heart cell destruction, similar to that seen in an active lesion when lymphocytes invade heart tissue, were observed. After 18 h incubation, about 65-70% of the lymphocytes were attached, larger, and rough surfaced. Inhibition of monocyte migration tests, each in the presence of the antigens of subcellular fractions of T. cruzi organisms and of allogeneic heart myofibers, indicated the presence of a cross-reacting antigen common to both the parasite and the heart in the small particle or membrane fractions. The particulate antigens of the 30,000 g, 35-min fraction of heart muscle gave rise to inhibition of monocyte migration as did the counterpart fraction derived from T. cruzi organisms. The destruction of nonparasitized target heart cells by T. cruzi-sensitized lymphocytes is an in vitro model of the chronic myocarditis of Chagas' disease, and the recognition of cross-reactive antigens of the host cell by T. cruzi-sensitized lymphocytes is believed to be the pathogenic basis for subsequent tissue injury in the chronic phase of this disease.

Between November 1993 and March 1994, a cluster 6 pediatric patients with acute febrile illnesses associated with rashes was identified in Jujuy Province, Argentina. Immunohistochemical staining of tissues confirmed spotted fever group rickettsial infection in a patient with fatal disease, and testing of serum of a patient convalescing from the illness by using an indirect immunofluorescence assay (IFA) demonstrated antibodies reactive with spotted fever group rickettsiae. A serosurvey was conducted among 16 households in proximity to the index case. Of 105 healthy subjects evaluated by IFA, 19 (18%) demonstrated antibodies reactive with rickettsiae or ehrlichiae: 4 had antibodies reactive with Rickettsia rickettsii, 15 with Ehrlichia chaffeensis, and 1 with R. typhi. Amblyomma cajennense, a known vector of R. rickettsii in South America, was collected from pets and horses in the area. These results are the first to document rickettsial spotted fever and ehrlichial infections in Argentina.

Eight rabbits that received a single inoculation of trypomastigotes of a virulent strain of Trypanosoma cruzi first developed a transient acute illness associated with parasitemia; later, 4 of these rabbits died with chronic myocarditis and/or with megacolon in the absence of demonstrable parasitemia or encysted parasites in tissues. Two of these rabbits with chronic myocarditis died unexpectedly. Three of the inoculated rabbits that survived the infection were sacrificed 18 months later and showed similar but less severe microscopic lesions. The remaining rabbit is alive and well at the time of writing (26 months) with negative blood cultures but high hemagglutinating antibody titers to T. cruzi antigens. The natural course of T. cruzi infection in rabbits and the lesions observed postmortem are similar to those recorded for humans with chronic Chagas' disease. Multiple injections of particulate subcellular antigens of T. cruzi in rabbits resulted in microscopic lesions similar to those observed in rabbits that survived protozoan infection. Sera of rabbits inoculated with T. cruzi have antibodies to striated and smooth muscle structures. However, evidence provided in this and in other experiments strongly suggest that the lesions of chronic Chagas' disease are produced by delayed hypersensitivity to T. cruzi antigens.

Chagas disease is the clinical condition triggered by infection with the protozoan Trypanosoma cruzi. The infection is transmitted by triatomine insects while blood feeding on a human host. Field studies predict that one third of an estimated 18 million T cruzi-infected humans in Latin America will die of Chagas disease. Acute infections are usually asymptomatic, but the ensuing chronic T cruzi infections have been associated with high ratios of morbidity and mortality: Chagas heart disease leads to unexpected death in 37.5% of patients, 58% develop heart failure and die and megacolon or megaoesophagus has been associated with death in 4.5%. The pathogenesis of Chagas disease appears to be related to a parasite-induced mutation of the vertebrate genome. Currently, treatment is unsatisfactory.