Hepatic Involvement in Hemophagocytic Lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome which results in uncontrolled systemic proliferation of benign macrophages in all reticuloendothelial organs producing worsening peripheral blood cytopenia(s); hypercytokinemia leading to hepatic injury producing hyperferritinemia, hypertriglyceridemia, hypofibrinogenemia; and if not diagnosed and treated early may lead to disseminated intravascular coagulation (DIC), multiorgan dysfunction, and death in nearly all individuals. It is postulated that hepatic injury/dysfunction starts early in the course of the disease which may mimic nonspecific hepatitis like prodrome to fulminant hepatic failure; possibly requiring liver transplant. While HLH as an entity is being increasingly recognized nowadays across wide specialties (both pediatric and adults); hepatic involvement in this setting has been poorly characterized. This chapter is aimed to highlight on the diagnosis and classification of HLH with a special emphasis on the pathophysiology of hepatic dysfunction, histomorphology of liver; and the current concept and controversies on the role of liver transplantation in this clinical setting

Compressive myeloradiculopathy from bony metastasis as the initial presentation of poorly differentiated adenocarcinoma stomach - a case report.

Carcinoma of the stomach rarely disseminates to bone. We report a case of compressive myeloradiculopathy from extensive metastases to the spine, which on evaluation originated from adenocarcinoma of the stomach. Magnetic resonance imaging of the spine showed osteolytic and osteosclerotic metastases. Gastrointestinal endoscopy revealed ulcerative growth in the stomach that on biopsy showed poorly differentiated adenocarcinoma. This case is unique in that the initial presentation of gastric cancer itself was bony metastases without any gastrointestinal symptoms or liver involvement. Moreover, metastases were osteosclerotic as well, which is against the general belief that gastric cancer produces only osteolytic secondaries

Selective myelosuppression following yellow phosphorus ingestion

Toxicity from accidental and intentional ingestion of yellow phosphorus, ubiquitously present in fireworks and rodenticides, has recently become more frequent. Gastrointestinal, renal, neurologic, and cardiovascular manifestations are common, with mortality of 23 per cent to 73 per cent. Reports of haematological abnormalities are rare. We report only the second case of severe neutropenia secondary to selective myelosuppression in a 14-year-old girl following intentional ingestion of yellow phosphorus. Leucocyte counts recovered spontaneously without further complications. Our case indicates that, besides hepatic and renal function monitoring, physicians should meticulously monitor blood counts in such cases for early detection of marrow suppression. Further studies are required to elucidate the complex mechanisms and significance of this unusual toxicity of yellow phosphorus

Chronic Myeloid Leukemia: Biology, Diagnosis, and Management

Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm characterized by florid myelo-megakaryocytic proliferation involving peripheral blood, bone marrow, and spleen. These results are due to balanced reciprocal translocation between long arm of chromosome 9 and 22 that produces a truncated chromosome 22 (Philadelphia chromosome) leading to fusion of BCR-ABL1 genes causing enhanced autonomous activation of tyrosine kinase and downstream cellular proliferation pathway. While targeted therapy with novel tyrosine kinase inhibitors (TKI) has revolutionized the outcome in such patients, occurrence of additional cytogenetic abnormalities, emergence of TKI resistance, and idiosyncratic marrow suppression following higher generation TKI therapy have posed newer management challenges in CML. This chapter is aimed to highlight the recent updates in the disease biology, stepwise diagnostic work-up, and management guidelines in CML with a brief highlight on the prospect of stem cell transplantation in such condition

Hemophagocytic lymphohistiocytosis: an unusual complication in Orientia tsutsugamushi disease (scrub typhus).

Background: Hemophagocytic lymphohistiocytosis (HLH) is an uncommon, potentially fatal, hyperinflammatory syndrome that may rarely complicate the clinical course of Orientia tsutsugamushi disease (scrub typhus). Methods: We describe here the clinicopathological features, laboratory parameters, management, and outcome data of three adult patients (1 female, 2 males) with scrub typhus associated HLH from a tertiary center with a brief and concise review of international literature. Results: All three patients satisfied the HLH-2004 diagnostic criteria; one had multi organ dysfunction with “sky high” ferritin level; and all had a dramatic recovery following doxycyclin therapy. Literature review from January 1990 to March 2014 revealed that scrub typhus associated HLH were reported in 21 patients, mostly from the scrub endemic countries of the world. These included 11 females and 10 males with mean age of 35 years (range; 8 months to 81 years). Fifteen of 17 patients (where data was available) had a favorable outcome following early serological diagnosis and initiation of definitive antibiotic therapy with (N=6) or without (N=9) immunosuppressive/immunomodulator therapy. Mutation analysis for primary HLH was performed in one patient only, and HLH-2004 protocol was used in two patients. Conclusion: We suggest that HLH should be considered in severe cases of scrub typhus especially if associated with cytopenia (s), liver dysfunction, and coagulation abnormalities.  Further studies are required to understand whether an immunosuppressive and/or immunomodulator therapy could be beneficial in those patients who remain unresponsive to definitive antibiotic therapy

CUTANEOUS HYPERPIGMENTATION IN MEGALOBLASTIC ANEMIA: A FIVE YEAR RETROSPECTIVE REVIEW.

Background: Cutaneous hyperpigmentation is an often overlooked clinical sign in megaloblastic anemia (MA) which has been sporadically reported in the literature. Methods: We describe the bone marrow (BM) changes and clinicolaboaratory characteristics of 25 of 198 adult cases (>16 years) with cutaneous hyperpigmentation who underwent BM evaluation for cytopenia (s). Results:  Twenty-one of 25 cases (84%) had MA, while MA without hyperpigmentation occurred only in 12 of remainder 173 cases (P0.05). In six cases where follow-up data were available, there was significant reversal of hyperpigmentation at 12 weeks following parenteral cobalamine therapy. In all five cases with pyrexia, fever subsided after 24 to 72 hours following administration of parenteral cobalamine therapy. Conclusion: Cutaneous hyperpigmentation, pyrexia, and cytopenia (s) are strongly associated with megaloblastic anemia. Knuckle pad hyperpigmentation is much more common than diffuse pigmentation of the palms and/or soles in such patents. A nonsignificant trend towards a greater degree of MA was found in cases with pigmentation of the knuckles

Renal cell carcinoma and plasma cell myeloma: Unique association and clinical implications

Several case series, in the recent past, have postulated an association between plasma cell myeloma (MM) and renal cell carcinoma (RCC). Population-based data have revealed a bi-directional association between these two malignancies, which points to shared risk factors, similar cytokine (Interleukin-6, IL-6) requirements for growth and survival, and overlapping clinical presentation. The presence of lytic lesions in a patient with prior RCC may simulate bone metastasis; thus, leading to a diagnostic pitfall with potentially adverse clinical implications. Besides these, therapeutic strategies employed for MM have been tried for RCCs with partial success. We aimed to describe two patients, aged 64 and 54 years, with RCC-MM association, with review of relevant literature; and create awareness among pathologists/hematologists, and oncologists. Elucidating a common genetic basis might throw some light in understanding the pathobiology of these tumors and development of newer targeted therapies