User:Coldbringer/sandbox

Gandy–Gamna nodules, Gandy–Gamna bodies or siderotic nodules are small yellow-brown, brown or rust-coloured foci found in the spleen in patients with splenomegaly due to portal hypertension and sickle cell disease. They consist of fibrous tissue with haemosiderin and calcium deposits, and probably form due to scarring at sites of small perivascular haemorrhages. They are visible on MRI scanning due to the presence of haemosiderin.

Other names include hemosiderotic nodules, Gandy-Gamna-De Gaetani areas , sclerosiderotic areas of Gandy-Gamna , Gandy-Gamna lesions , sclerotic calciosiderosis , sclerosiderotic granulomatosis. and because of their rusty colour on gross inspection, tobacco flecks.

Etiology and structure
Gamna-Gandy bodies are thought to result from small local perivascular hemorrhages and necrosis in the splenic parenchyma, followed by fibrosis. Breakdown of hemoglobin produces hemosiderin deposits, that, together with calcium salt precipitates, impregnate degraded collagen and elastic fibres. On section, many of the iron-containing filaments are continuous with normal elastic fibers.

Tedeschi indicated a number of components of the Gamna-Gandy bodies: various sizes of blood vessels with aberrations varying of a nonspecific type of vasculitis to sclerosis and hyalinisation with obliteration or narrowing of the lumina, calcium precipitates (demonstrated by the von Kossa stain) and hemosiderin deposits (demonstrated by the Gömöri iron stain), present in varying amounts in the walls of vessels and in stroma, and a prominent fibroblastic and macrophagic reaction with the production of multinucleated foreign body giant cells. These can have as many as 70 nuclei on one section, and can contain yellowish-green rods or crystalline material. Spheroid, semilunar, or thread-like ("bamboo-shaped") fibers which resemble mycelial structures or parasitic eggs are the hallmark of the Gamna-Gandy bodies.

Macroscopy
On fresh sections, Gamna-Gandy bodies appear as circumscribed lesions measuring a couple of millimetres up to a centimetre or more, having a red rim, a pale inner zone and a brown center. These colours darken with exposure to oxygen.

Image Dufour macroscopy GGB.

Mechanism of formation
To do: Piccin mechanism of distribution of GGB. (possibly image of spleen with red and white pulp)

Associations
Splenic Gamna-Gandy bodies have been found in the following disorders or pathological entities:
 * Liver cirrhosis, of varying etiologies (including hereditary hemochromatosis)
 * Hereditary hemochromatosis
 * Sickle-cell disease
 * Splenic angiosarcoma
 * Schistosomiasis
 * Chronic myelogenous leukemia
 * Paroxysmal nocturnal hemoglobinuria

Although the spleen appears to be the organ in which Gamna-Gandy bodies are most often found, they have also been reported in other organs of the body:
 * Atrial myxoma
 * Adenomatous colorectal polyp
 * Thyroid adenoma (one of which was follicular)
 * Renal carcinoma (one of which was a clear cell variant)
 * Thymoma
 * Retroperitoneal lymph nodes near cirrhotic livers
 * Central and peripheral nervous system: metastatic melanoma, schwannoma of ulnar nerve, cholesterol granuloma of temporal bone, benign sacral cyst, pituitary adenoma, cavernous hemangioma, myxopapillary ependymoma, supratentorial primitive neuroectodermal tumor (PNET), anaplastic oligodendroglioma, brain abscess with hemorrhage, and anaplastic meningioma

Imaging
Ultrasound, MRI/CT (picture Bhatt)

Clinical significance
Mimickers of GGB (Bhatt)

Epidemiology
Kleinschmidt, argument that they are quite common if you look for them.

In animals
Gamna-Gandy bodies have been incidental findings in the spleens of beagles used in toxicologic studies. In another study of spontaneous findings in beagles used for toxicologic studies, an incidence of 43.1% of Gamna-Gandy-like bodies of the splenic capsule was reported.

Experimentation
Gamna-Gandy bodies have been produced experimentally in the spleens of felines, canines and rabbits by intraparenchymatous injections of alcohol and calcium chloride, by caustics and by diathermy. Ligation of the splenic veins near the splenic hilum produced necrosis and variable amounts of Gamna-Gandy bodies in these animals; the best result was produced in canines.

History
Gamna-Gandy bodies were first mentioned by Italian physician Marini in 1902 and by Stengel in 1904 in case reports of patients with splenomegaly and hepatic cirrhosis. These bodies were given their eponymous name after they were reported by Charles Gandy (1872-1943) in 1905 and Carlo Gamna (1866-1950) in 1921, describing them in the spleen of a patient with biliary cirrhosis and in splenic blood vessels in hemolytic siderosis, respectively. Gamna called them siderotic splenogranulomatosis, and explained their presence as resulting from small local hemorrhages, with degeneration and subsequent deposition of iron and calcium salts.

Fungal origin
Thread-like structures are sometimes found in Gamna-Gandy bodies, prompting belief by some that these were mycelial hyphae, and that the causative agent of splenomegaly was fungal in origin (giving rise to terms such as splenomycosis and mycotic splenomegaly). Others regarded these filaments as mycelial but believed the fungus to be a secondary invader and not of etiologic significance. The fungal belief was strengthened by findings of fungi of the Aspergillus and Helminthosporium genera in some enlarged spleens. Abrikossoff reviewed these findings and could not find compelling evidence for either presence of Aspergillus nor an etiological link with splenomegaly, concluding that the threads were incrustations of iron in tissue fibers.

Reimann and Kurotchkin examined these findings in 1931 and found that the Helminthosporium was without virulence for laboratory animals, and could not culture any fungi in primary chronic splenomegaly without liver cirrhosis, nor in selected other splenic diseases. The appearance of the filaments in the Gamna-Gandy bodies did not conform with that of hyphae cultured from the same spleen. Introducing Helminthosporium in laboratory monkeys in various ways did not produce any Gamna-Gandy bodies in the spleen. Reimann and Kurotchkin thus concluded that Gamna-Gandy bodies are not caused by the growth or presence of fungi.