Introduction

Gelatinous transformation of bone marrow (GTM) is a rare disorder of unknown pathogenesis, characterized by fat cell atrophy, loss of hematopoietic cells and deposition of extracellular gelatinous substances, which histochemically are mucopolysaccharides rich in hyaluronic acid.(1) Its incidence and severity is maximum in young adults. The various conditions associated with GTM include malnutrition, Anorexia Nervosa, AIDS, Lymphomas, Carcinoma and Chronic Heart Failure.(2)

Case Report

A male child was born with Hemolytic Disease of Newborn due to Rh incompatibility (Mother was O negative and baby was O positive with DCT 3+. The neonate was appropriately managed and 2 units of packed cells were transfused. At 1 month, DCT was negative, Jaundice and Hepatosplenomegaly subsided, however pallor still persisted. On Complete Blood Count, there was severe anemia (Hemoglobin=6.9g/dL and RBC=2.34x10⁶/uL). Reticulocyte count was 1.04% and Reticulocyte Hemoglobin:31.3 pg. Total leucocyte count and platelet count were within normal limits.

Peripheral smear examination revealed predominantly normocytic normochromic red blood cells with mild anisocytosis with presence of few elliptocytes and microcytes. Occasional nucleated red blood cell was seen on screening. DLC was within normal limits. Platelets were adequate.

Bone marrow aspirate smears showed maturing cells of erythroid, myeloid and megakaryocytic lineage. Abundant, extracellular, amorphous matrix material was identified which was pink purple in colour on Wright Giemsa staining. (Figure. 1) It showed positive staining for Periodic Acid-Schiff (PAS) and Alcian Blue (pH=2.5). (Figure. 2) These features were suggestive of Gelatinous Transformation of Bone Marrow.

Figure 1: Giemsa Wright stain, 400x: BMA smear showing bright pinkish purple material.	Figure 2: PAS stain, 400x: Extracellular material showing PAS positive.

Discussion

Gelatinous transformation is also referred as “serous fat atrophy” or “starvation marrow”.(2,3) In 1930, Paul Michael was the first to document 11 instances of GTM in the bone marrow of autopsied individuals.(4) GMT presents as an extracellular eosinophilic amorphous material which stains pinkish-purple on Romanowsky-stained bone marrow preparations. It stains pink on PAS (resistant to Diastase) and stains blue on Alcian Blue (especially at pH 2.5) showing positivity on both the stains.(5) Electron microscopy has shown that the fibrillar material of GMT bears some resemblance to amyloid fibrils.(6) Although GTM is associated with a wide spectrum of conditions (malnutrition, anorexia nervosa, AIDS, lymphomas, carcinoma and chronic heart failure), the exact causes are still unclear. (2) It has been reported to be a reversible condition if the underlying disorder can be eliminated. Disruption of the hematopoietic microenvironment plays an important role in gelatinous degeneration. In cases of chronic infections, proliferation of macrophages has been implicated in gelatinous degeneration associated with impaired hematopoiesis. Macrophages secrete TNF, which inhibits hematopoietic progenitor cell growth and may contribute to anemia by promoting dyserythropoiesis.(1) "Stress factors" linked to acute fevers in intensive care or multi-organ failure patients may contribute to the development of GMT.(3)

Morphologically, it is important to distinguish this condition from bone marrow edema, bone marrow necrosis and amyloidosis (Table 1).(4)

In the current study, extensive gelatinous transformation was identified on Bone Marrow Aspirate smears of a neonate with a history of Hemolytic Disease of Newborn due to Rh incompatibility. This is a rare occurrence. The only significant finding on CBC was persistent anemia.

The pink-purple material in bone marrow has been noted in preparations associated with cachectic diseases resulting from chronic disorder.(3) The lack of suspicion and awareness regarding this pathologic entity has led to misdiagnosis and delayed diagnosis.

GTM has been reported in varied number of conditions in past literature (Table 2).(4) In a study by Michael et al. (1930), 11 autopsied cases were reported where Tuberculosis and malignancies were associated conditions with GTM and anemia was identified in 10 cases.(7) Studies done by Tavassoli et al. (1976) and Seaman et al. (1978) revealed Anorexia Nervosa or starvation as most commonly associated condition with GTM.(6,7) Bohm et al. (2000) observed 158 cases where the spectrum of underlying diseases was heterogeneous and age dependent with all showing anemia.(2) In a study by Sen et al. (2003) of 65 cases, GMT was most commonly associated with infections with all cases presenting with anemia.(3) In another study by Khera et al. (2018) of 109 cases highlighted nutritional deficiencies and post-chemotherapy conditions, with all cases presenting with anemia.(1)

Most authors suggest that the deposition of hyaluronic acid in GMT lesions may contribute to the development of anemia, as recent studies have indicated that natural polysaccharides are not conducive to hematopoietic proliferation.

Conclusion

GTM is associated with a wide spectrum of conditions and may serve as an indicator of severe illness rather than a specific disease [2]. The range of diseases linked to GMT suggests it results from fundamental bioregulatory processes activated in various pathological states, leading to similar lesions in the bone marrow. Further clinicopathological studies are needed for patients at high risk of developing GMT to better understand the mechanisms behind these lesions.

References

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