Gamna-Gandy Bodies Research Articles

Therapeutic efficacy of Punarnavadi mandura against phenylhydrazine-induced hemolytic anemia in rats

Background & aimHemolytic anemia is a blood disorder whose incidence is increasing in the world in recent years especially after the pandemic. Conventional treatments include use of steroids and immunosuppresants that are accompanied by numerous adverse effects. With growing interest in using complex multi-component formulations for multi-targeted therapy, the present study aims to investigate the therapeutic efficacy of a traditional Ayurvedic herbomineral preparation, Punarnavadi Mandura, which has been traditionally used as a supplement in iron-deficiency anemia, against phenylhydrazine-induced hemolytic anemia in rodent models. Experimental approachesWe employ a combination of in vivo and in silico methods in this work to study the therapeutic potential and to understand the possible molecular targets of this traditional formulation. Conventional drugs prednisolone and ferrous sulphate were used for comparison. Results and conclusionThe in vivo studies confirm the ability of Punarnavadi Mandura to reverse pathological changes associated with hemolytic anemia at 100 mg/kg and 200 mg/kg concentration. It restored hemoglobin, bilirubin and white blood cell levels to normal and reduced reticulocytes, hemosiderin and Gamna Gandy bodies in the liver, spleen and kidney. In silico studies suggested that the key constituents in Punarnavadi Mandura interact with high affinity to erythropoietic receptor which could contribute to erythropoiesis. The in silico study also predicted that the phytoconstituents of Punarnavadi Mandura could inhibit TNF-α activity which was validated using gene expression studies.

Death due to sickle cell crisis: a case report.

Sickle cell disease (SCD) is the most common hereditary hemoglobinopathy worldwide. It results in characteristic acute and chronic findings on postmortem computed tomography (PMCT), macroscopic and microscopic examinations. While the diagnostic imaging and macroscopic features are not specific for SCD on their own, when coupled with microscopic features such as sickled erythrocytes and evidence of chronic venous congestion (i.e., Gamna-Gandy bodies), these clues can help alert forensic pathologists to the presence of SCD. Despite the prevalence of the disease and the constellation of findings alluded to above, SCD is not often explored in forensic pathology literature. This case demonstrates classic acute and chronic features of SCD on PMCT, macroscopic and microscopic examinations. It explores the pathophysiology leading to sudden and unexpected death in a person with SCD and possible pitfalls in attribution of cause of death.

SICKLE CELL THALASSEMIA IN AN ADULT FROM CENTRAL INDIA SHOWING MASSIVE SPLENIC INFARCTION AND GAMNA-GANDY BODIES IN SPLENIC PARENCHYMA WITH CONCOMITANT PLASMODIUM FALCIPARUM INFECTION

Background. Sickle cell thalassemia is a heterozygous state of HbS/β+ or HbS/β0 manifested clinically either as an asymptomatic carrier or have features akin to sickle cell anemia. Objective. The aim of the study is to review the literature and discuss the varied clinical manifestations and diagnosis of a case report of haemoglobinopathy in an adult from Central India. Methods. A case of haemoglobinopathy from central part of India is being investigated. Results. A case of haemoglobinopathy in an adult presenting to a tertiary hospital with chronic back ache was reported. The patient was found to have massive splenomegaly with evidence of splenic infarction. Gross examination of spleen revealed multiple soft yellowish pasty areas, which on microscopic examination showed significant necrosis with presence of great amount pale amorphous yellow substance, Gamna-Gandy bodies (GGBs) and massive foreign body cell reaction in splenic parenchyma. Post-splenectomy peripheral blood smear (PBS) showed thrombocytosis and plasmodium falciparum gametocytes. The Hb electrophoresis revealed both elevation of Hb S (49.7%), Hb F (46.7%); Hb A2 (3.0%) and (Hb A 0.7%) consistent with as Sickle Cell Thalassemia Hb S/β+ Thalassemia. Conclusion. Sickle cell thalassemia with long standing huge splenomegaly, splenic infarction with GGBs deposition and concomitant falciparum malaria in clinically stable patient is rare indeed.

Gamna Gandy Bodies: The Tobacco Flex appearance

Splenic siderotic nodules, also known as Gamna Gandi’s bodies are nodules containing hemosiderin, fibrous tissue and calcium and result of small necrotic haemorrhagic focis in the spleen with a fibroblastic reaction leading to microarchitectural distorsion. Anatomopathological examination show bamboo-shaped small circumscribed nodular siderotic deposits corresponding to fibrous collagenous tissue, impregnated with iron pigments (hemosiderin) and calcium. Herein, we display images of Gamna Gandi’s bodies in a 55-year-old patient with a history of chronic portal thrombosis resulting in portal hypertension. Gamna Gandi’s bodies are easily detected, in most cases on the various cross-sectional imaging techniques as a well-circumscribed millimeteric nodules, with a black central hemorrhage surrounded by a double rim, a pale inner hyperemic rim and a dark outer rim, giving an appearance of “tobacco flecks” (figure 2, D, arrow).

Renal oncocytoma with prominent xanthomatous reaction. A rare histopathological variant of oncocytoma.

Renal oncocytoma (RO) is a distinctive neoplasm with a well-recognized gross and cytoarchitectural appearance. However, on some occasions, it may show uncommon, atypical, or worrisome gross and microscopic features potentially generating diagnostic difficulties. We herein review the oncocytoma variant characterized by a significant intraneoplastic xanthomatous reaction that produces a variegated macroscopic appearance. This feature may pose a genuine diagnostic problem with conventional (clear cell) renal cell carcinoma (RCC) because this reaction creates a departure from the typical uniform, tan-brown appearance of oncocytoma. The microscopic presence of foamy macrophages in RO may potentially lead to diagnostic difficulties with tumors exhibiting eosinophilic cells and significant infiltration for lipid-laden foamy macrophages such as cystic RCC, unclassified RCC rich in foamy macrophages, the solid variant of papillary RCC with oncocytic features, post-neuroblastoma RCC, succinate dehydrogenase-deficient RCC, mucinous-poor tubular and spindle cell carcinoma, and the oncocytic variant of the epithelioid angiomyolipoma. In conflictive cases, an immunohistochemical panel should help to solve the diagnostic problem. Therefore, the presence of abundant foamy macrophages should not dissuade the pathologist from establishing a diagnosis of RO. Prominent xanthomatous reaction despite its low frequency (4.3%) can be considered an additional feature of RO. Thus, RO should be added to the list of renal tumors that can show a significant reaction of lipid-laden foamy macrophages. Besides, Gamna–Gandy bodies can be present in this tumor.

Prediction of Sufficient Liver Enhancement on the Gadoxetate Disodium-enhanced Hepatobiliary Phase Imaging Using Transitional Phase Images and Albumin-bilirubin Grade.

Purpose:To investigate whether the contrast enhancement effect in hepatobiliary phase (HBP) images can be predicted using transitional phase (3-min delay) images on liver magnetic resonance imaging (MRI) based on the quantitative liver–spleen contrast ratio (Q-LSC) and albumin–bilirubin (ALBI) grade.Methods:Overall, 212 patients (124 men and 88 women; mean age 66.7 ± 11.1 years) who underwent blood tests (assessed within 1 month of performing MRI) were included; patients with diffuse tumor, hepatectomy, splenectomy, Gamna–Gandy bodies in the spleen, and movement artifacts were excluded. Q-LSC was calculated using the signal intensity of the liver divided that of the spleen. Q-LSC > 1.5 (cut-off value) indicates a relatively higher sensitivity for detecting of hepatic lesions. To predict the contrast enhancement effect in HBP using Q-LSC of 3-min delay images, Q-LSC of 10- and 15-min delay images were compared for each ALBI grade based on Q-LSC of 3-min delay images. Furthermore, to verify the accuracy of this prediction, the proportion of cases with Q-LSC > 1.5 in 10- and 15 min delay images was calculated based on Q-LSC on 3-min delay images.Results:The higher the Q-LSC on the 3-min delay image, the higher was the Q-LSC on its 10- and 15-min delay images. The proportion of cases with Q-LSC > 1.5 in 10- and 15-min delay images was higher for ALBI grade 1 than for ALBI grades 2 and 3 even in the same Q-LSC on 3-min delay images. Q-LSC was <1 in a 3-min delay image and <1.5 in a 15-min delay image in 62.2% of patients with ALBI grade 1 and 82.1% of patients with ALBI grades 2 and 3.Conclusion:The liver contrast enhancement effect in HBP images could be predicted using a 3-min delay image based on Q-LSC and ALBI grade.

Incidental splenic findings in pancreatosplenectomy specimens resected for primary pancreatic lesions.

Little has been written on the frequency and nature of incidental splenic lesions diagnosed on histopathological examination of pancreatosplenectomy specimens. For 191 such specimens, incidental histological findings after haematopathologist re-review were tabulated. Cases suspicious for lymphoid malignancy underwent molecular analysis for immunoglobulin heavy and kappa light chain rearrangement. Follow-up was obtained on selected cases. In five cases (3%), the spleen was sampled but not mentioned in the original microscopic report; all were normal on re-review. Otherwise, most (171 of 186, 92%) were initially diagnosed as normal, with 160 (94%) remaining so on re-review. Findings on re-review not initially described (n=11, 6%) included four cases with splenic morphology suspicious for possible leukaemia/lymphoma involvement. Additional findings included abscess formation, foamy macrophages, necrotising granulomas and simple cysts. Fifteen spleens were initially diagnosed as abnormal; the histopathological process was confirmed in all, including non-necrotising granulomas, cysts, Gamna-Gandy bodies, foamy macrophages, involvement by pancreatic neoplasm and involvement by known chronic lymphocytic leukaemia (CLL). Molecular analysis was performed on the five cases of known/suspected lymphoma and two were positive for monoclonal gene rearrangement, including the known CLL and a previously undiagnosed case with similar immunophenotype. Incidental splenic findings are not uncommon in pancreatosplenectomy specimens. While most are of limited clinical significance, low-grade lymphoproliferative disorders may go undetected if the spleen is overlooked. We recommend careful observation of splenic findings in these specimens, with a low threshold for haematopathological consultation when in doubt.

Gamna-Gandy bodies of the spleen in sickle cell disease.

Gamna-Gandy bodies of the spleen in sickle cell disease.

Spleen histology in children with sickle cell disease and hereditary spherocytosis: hints on the disease pathophysiology

Hereditary spherocytosis (HS) and sickle cell disease (SCD) are associated with splenomegaly and spleen dysfunction in pediatric patients. Scant data exist on possible correlations between spleen morphology and function in HS and SCD. This study aimed to assess the histologic and morphometric features of HS and SCD spleens, to get possible correlations with disease pathophysiology. In a large series of spleens from SCD, HS, and control patients, the following parameters were considered: (i) macroscopic features, (ii) lymphoid follicle (LF) density, (iii) presence of perifollicular marginal zones, (iv) presence of Gamna-Gandy bodies, (v) density of CD8-positive sinusoids, (vi) density of CD34-positive microvessels, (vii) presence/distribution of fibrosis and smooth muscle actin (SMA)-positive myoid cells, and (viii) density of CD68-positive macrophages. SCD and HS spleens had similar macroscopic features. SCD spleens had lower LF density and fewer marginal zones than did HS spleens and controls. SCD also showed lower CD8-positive sinusoid density, increased CD34-positive microvessel density and SMA-positive myoid cells, and higher prevalence of fibrosis and Gamna-Gandy bodies. HS had lower LF and CD8-positive sinusoid density than did controls. No significant differences were noted in red pulp macrophages. By multivariate analysis, most HS spleens clustered with controls, whereas SCD grouped separately. A multiparametric score could predict the degree of spleen changes irrespective of the underlying disease. In conclusion, SCD spleens display greater histologic effacement than HS, and SCD-related changes suggest impaired function due to vascular damage. These observations may contribute to guide the clinical management of patients.

The effects of hematopoietic stem cell transplant on splenic extramedullary hematopoiesis in patients with myeloproliferative neoplasm-associated myelofibrosis

Background/objectiveHematopoietic stem cell transplant (HSCT) is the only curative treatment for myeloproliferative neoplasm-associated myelofibrosis (MPN-MF). The main clinical manifestation of MPN-MF is splenomegaly secondary to extramedullary hematopoiesis (EMH). The effects of HSCT on splenic EMH and associated vascular and stromal changes are unknown. This study compares the findings seen in spleens following HSCT with those of nontransplanted patients, normal controls, and matched bone marrow (BM) samples. MethodsThis study included three transplanted MPN-MF spleens, three nontransplanted MPN-MF spleens, and three normal controls. Spleens were assessed for: (a) presence/extent of EMH; (b) presence of Gamna–Gandy bodies; (c) splenic fibrosis; (d) CD34-positive microvessel density; (e) CD8-positive sinusoids; (f) frequency of smooth muscle actin-positive myoid cells; and (g) nerve growth factor receptor-positive adventitial reticulum cells. In two cases, matched BM samples were assessed for cellularity, presence of atypical megakaryocytes, and fibrosis. ResultsCompared with normal controls, all MPN-MF spleens were larger in size, had EMH, red pulp fibrosis, higher CD34-positive microvessel density, and decreased CD8-positive sinusoids. Compared with nontransplanted cases, post-HSCT spleens showed disappearance or reduction of EMH. Gamna–Gandy bodies were increased; no differences in the remaining parameters were found. A reduction of splenic EMH was associated with normalization of BM cellularity and megakaryopoiesis. ConclusionHSCT reduces/abrogates splenic EMH and is associated with an increased number of Gamna–Gandy bodies, which may suggest vascular damage. The lack of stromal changes in spleens removed shortly after transplant is in line with similar observations in the BM, where a longer interval is often necessary for resolution of fibrosis.

A novel method for evaluating enhancement using gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid in the hepatobiliary phase of magnetic resonance imaging

To investigate whether quantitative liver-portal vein contrast ratio (Q-LPC) can be used as a substitute for quantitative liver-spleen contrast ratio (Q-LSC) in the hepatobiliary phase (HBP) contrasting degree. Q-LSC and Q-LPC were calculated in HBP images that were obtained approximately 20 min after gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid injection, and relationship between them was evaluated. A very strong correlation was observed between Q-LSC and Q-LPC with respect to Child–Pugh class. Furthermore, Q-LPC values were not significantly different between patients with splenectomy or Gamna–Gandy bodies and those without. Therefore, Q-LPC can be useful instead of Q-LSC in patients with splenectomy or Gamna–Gandy bodies.

Cardiac incidentaloma during endoscopic ultrasound: cardiac myxoma with Gamna–Gandy bodies

Cardiac incidentaloma during endoscopic ultrasound: cardiac myxoma with Gamna–Gandy bodies

Gamna‐Gandy bodies: a case of mistaken identity in the spleen of a cat

A 4-year-old, female spayed Domestic Shorthair cat was presented for a 2-day history of lethargy, anorexia, and vomiting. Diagnostic assessments revealed a severe, regenerative anemia and the presence of a solitary, 3 × 4 cm splenic mass. Cytologic examination of fine-needle aspirates of the splenic mass showed sheets of pleomorphic histiocytic cells with numerous intracellular and extracellular, negatively staining to deeply basophilic, branching structures. These structures were typically of thin uniform thickness with random angled branching that formed geometrical shapes and fragments, occasionally with sharpened ends and a crystalline appearance. Septal-like divisions were irregularly spaced along some of the linear branches. The cytology was interpreted as a probable histiocytic inflammatory response to the unidentified foreign material with histiocytic sarcoma as a differential diagnosis. Histopathologic evaluation of the splenic mass resulted in a diagnosis of histiocytic sarcoma. The branching material stained positively for both iron and calcium, indicating that the material was compatible with Gamna-Gandy bodies present secondary to tumor-associated hemorrhage and the formation of calcium-iron complexes.

症例 MRIで大量の鉄沈着が診断され,病理組織学的にGamna-Gandy結節様病変が検出された左房粘液腫の1例

症例 MRIで大量の鉄沈着が診断され,病理組織学的にGamna-Gandy結節様病変が検出された左房粘液腫の1例

Gamna-Gandy Bodies of the Spleen Detected with Susceptibility Weighted Imaging: Maybe a New Potential Non-Invasive Marker of Esophageal Varices

Background/ObjectivesPortal hypertension (PH) is a clinical sequelae of liver cirrhosis, and bleeding from esophageal varices (EV) is a serious complication of PH with significant morbidity and mortality. The aims of this study were to assess the ability of 2D multislice breath-hold susceptibility weighted imaging (SWI) to detect Gamna-Gandy bodies (GGBs) in the spleens of patients with PH and to evaluate the potential role of GGB number as a non-invasive marker of PH and EV.Materials and MethodsT1-, T2- and T2*- weighted imaging and SWI were performed on 135 patients with PH and on 37 control individuals. Platelet counts were collected from all PH patients. Two radiologists analyzed all magnetic resonance imaging (MRI) data, and measured the portal vein diameter, splenic index (SI), and platelet count/spleen diameter ratio. The numbers of patients with GGBs in the spleen were determined, and the numbers of GGB were counted in the four MRI sequences in GGB-positive patients. The portal vein diameter, SI, platelet count, and platelet count/spleen diameter ratio of control individuals were compared with those of GGB-negative and GGB-positive patients on SWI images. The correlations among GGB numbers, the portal vein diameter, the SI, the platelet count, and the platelet count/spleen diameter ratio were analyzed.ResultsThe GGB detection rate and the detected GGB number by using SWI were significantly greater than those by using T1-, T2-, and T2*- weighted images. The number of GGBs in the SWI images correlated positively with the portal vein diameter and SI and correlated negatively with the platelet count and platelet count/spleen diameter ratio.ConclusionSWI provided more accurate information of GGBs in patients with PH. The number of GGB may be a non-invasive predictor of improving the selection for endoscopic screening of PH patients at risk of EV.

Extreme acute anemia in an adult sickle cell disease patient: look at the spleen

Dear Editor, A 27-year-old male with known homozygous (HbSS) sickle cell disease (SCD) was admitted to our medical intensive care unit for coma and extreme anemia. He had suffered mild occasional painful osseous vasoocclusive crises and had never received a blood transfusion except for during hip osteonecrosis surgery at the age of 17. He started complaining of lower limb and back pain for a couple of days followed by an intense abdominal pain and several episodes of lipothymia, and was admitted to the emergency room for coma (Glasgow coma scale of 3/15). On admission, his temperature was 36.9 C, blood pressure 109/70 mmHg, heart rate 140/min; extreme conjunctival pallor was noted, as well as an enlarged spleen. Laboratory tests revealed an extremely low hemoglobin level (1.7 g/ dL), low reticulocyte (49 9 10/L) and platelet counts (95 9 10/L), increased white blood cell counts (23 9 10/L), arterial lactates (15 mmol/L), and plasma lactate dehydrogenase (LDH) (2,300 IU/L, N \ 200 IU/L) levels with a normal value of total bilirubin (14 lmol/L, N \ 17 lmol/L). The patient was immediately intubated and mechanically ventilated. A thoraco-abdominal CT scan excluded an internal hemorrhage but evidenced a splenomegaly (17 cm in the antero-posterior axis). Emergency packed erythrocyte transfusion (n = 5) and splenectomy were performed. The spleen was enlarged (19 9 14 9 10 cm), congestive, and hemorrhagic. Pathologic examination showed marked congestion and clogging of splenic cords by sickled red blood cells and Gamna–Gandy bodies (Fig. 1), compatible with an acute splenic sequestration (ASS). Blood cultures, Parvovirus B19 PCR, and serology tests were negative. The patient was successfully extubated 2 days after surgery and was discharged home 2 weeks later. He was asymptomatic 3 months after surgery.

Composition and significance of splenic Gamna-Gandy bodies in sickle cell anemia

Children with sickle cell anemia may undergo acute splenic sequestration. Splenectomy is performed in an attempt to reduce further events. Histologic studies of spleens have revealed the presence of granuloma-like nodules, known as Gamna-Gandy bodies with amorphous inclusions; however, their significance is unknown. The medical case records and histologic samples of consecutive children with sickle cell anemia treated with splenectomy between 2001 and 2007 at Our Lady's Children's Hospital, Dublin, were reviewed. Seventeen patients were identified. Gamna-Gandy bodies were studied by scanning electron microscopy and x-ray fluorescence spectroscopy. Gamna-Gandy bodies were identified in 7 (41%) patients, and amorphous inclusions were always seen. Patient age correlated significantly with Gamna-Gandy bodies (P = .002). Scanning electron microscopic analysis demonstrated the crystalline nature of Gamna-Gandy bodies and the chemical composition (C 47.1%; O(2) 29.7%; P 9.0%; K(+) 0.4%; Ca(2+) 6.4%; Fe(2+) 7.4%), whereas x-ray diffraction studied the structure (CaPO(4) ∙ FeOH). A crystal-formation gradient was observed, increasing from the red pulp to the white pulp. Our study shows that Gamna-Gandy bodies contain crystals and that their formation is age dependent. We also demonstrated the crystal structure and chemical composition and the relationship between Gamna-Gandy bodies and chest crises presplenectomy or postsplenectomy.

Corpuscules de Gamna-Gandy dans la cirrhose : un signe sans intérêt ?

PurposeTo determine the presence of Gamna-Gandy bodies (GGB) on MRI in patients with liver cirrhosis. Patients and methodsA total of 117 consecutive patients with cirrhosis followed-up by MRI were retrospectively reviewed. Two groups were defined: the first group included patients with GGB on MRI (n=15), the other group included patients without GGB (n=102). Both characteristics of groups were reviewed using standard cirrhosis criteria evaluation: sex, age, etiology of cirrhosis, Child-Pugh score, presence of esophageal varices, splenomegaly, ascitis, recanalization of the periumbilical veins, and presence of hepatic encephalopathy. Fisher's exact test and student t-test were used to compare both groups. ResultsGGB were more frequently observed in patients with splenomegaly (P=0.035). Hemochromatosis was the only etiology for cirrhosis statistically correlated to the presence of GGB (P=0.006) in our series. No other statistically significant association was noted between GGB and other characteristics of our cirrhotic patients. ConclusionEasily identified on all MRI pulse sequences, GGB do not correlate with the severity of cirrhosis. However, they are strongly correlated with the presence of splenomegaly and may be the result of segmental splenic hypertension. They are frequent in patients with hemochromatosis.

Histopathologic and Clinical Characterization of Atrial Myxoma: A Review of 19 Cases

Background Atrial myxomas are the most common cardiac neoplasms. They consist of 2 macroscopic features of solid, papillary, and myxoma cells in abundant mucopolysaccharide stroma in microscopic examination. The majority of patients may experience central or peripheral embolization, intracardiac obstruction, or constitutional symptoms. We sought to investigate the clinical presentation and pathological features of atrial myxomas in the population that underwent cardiac surgery at our institution. Methods Nineteen patients undergoing atrial myxoma excision were collected prospectively from the 18,300 patients who underwent cardiac surgery between January 2001 and June 2008 at Tehran Heart Center. Results Our study population consisted of 8 men and 11 women with a mean age of 54.05 ± 7.33 years. All of the cases had left atrial tumors. The solid myxoma group (79%) was comprised of 8 females and 7 males, while papillary myxoma (21%) was detected in 3 females and 1 male. In our study, 6 patients (32%) had hypertension (HTN), 4 (21%) had diabetes mellitus, and 5 (26.3%) had hyperlipidemia. Smoking and opium addiction were detected in 6 (32%) and 3 (16%) patients, respectively. Dyspnea was the most prevalent presenting symptom occurring in 12 patients (63%), followed by chest pain in 7 (37%), and neurological symptoms in 5 (26%). Hypertension was more prevalent in the patients with neurological symptoms than in those without them ( P =0.046). Five patients were anemic, and 5 cases had leukocytosis. Anemia was detected in 75% of the patients with papillary tumors compared to 13.3% of the patients with solid tumors ( P =0.037). Thrombocytosis was detected in 1 patient. Plasma cells infiltration were found in 1 papillary and 14 solid tumors. Neutrophils were detected in 9 solid and 1 papillary tumor. Three solid tumors revealed mineralized circumscribed nodules (Gamna-Gandy bodies). In patients with chest pain, the neutrophil count in the tumor tissue, not in the blood, was not significantly different from that observed in patients without chest pain (85.7% vs. 33.3%, respectively, P =0.057). Discussion Our data demonstrated the histological features of atrial myxomas correlated to some of the patients’ clinical findings. This study identifies for the first time the correlation between HTN and CNS symptoms in atrial myxoma. The presence of these findings could be due to the production of different mediators such as interleukins. However, further studies are needed to confirm these findings.

Gamna-Gandy bodies from cardiac myxoma on intraoperative cytology

Gamna-Gandy bodies from cardiac myxoma on intraoperative cytology