Blood and BM Path Chapter 5 - Pathology of the Marrow Flashcards
Cells that are not captured well by bone marrow aspirate
Megakaryocytes and macrophages
Hypo- and Hyper-cellularity cutoffs
Hypo: <25% cells
Hyper: >75% cells
Typical M:E ratio
BM Smear: 2.0-8.3
Histologic section: 1.5-3.0
Kala azar
Visceral leishmaniasis
Pearson syndrome
Mitochondrial cytopathy with recognizable features on BM biopsy.
Most cases are sporadic, but can be maternally (mitochondrially) or autosomally inherited.
Characterized by sideroblastic anemia with pancytopenia, exocrine pancreatic dysfunction, and hepatic dysfunction.
Histologically, BM reveals a hypoplastic anemia with ringed sideroblasts and vacuoles in many cell lineages.
Reactive plasmacytosis vs multiple myeloma
What is the normal kappa / lambda ratio?
About 2:1
Langerhans cell histiocytosis
Clonal proliferation of Langerhans cells
Characteristic LCH features: Cells are CD1a and S100 positive, have Birbeck granules on EM.
Has a peak incidence in childhood (~5-10 years of age).
Often causes osseous swelling and pathologic fractures. Appears as an osteolytic lesion on X-ray. The skull is the most common site.
May be accompanied by a brown-to-purple papular or eczematous rash. Hepatosplenomegaly and lymphadenopathy are often present. Hypopitutarism is an important assocation, and may manifest as central diabetes insipidus.
Juvenile xanthogranuloma
Benign proliferative histiocytic proliferation. Most commonly seen in kids (hence juvenile).
Clinical: Solitary red-brown, yellowish papule or nodule.
Histological: Presence of histiocytes, foam cells, and Touton giant cells (the fat-filled type).
Generally spontaneously resolve after a few years.
Erdheimer-Chester disease
Clonal proliferation of histiocytes
Almost always involves bone, especially bones of the lower extremities. ~50% of cases also have extraosseous manifestations (retroperitoneal, cardiovascular, lungs, kidneys). Caused by an activating mutation in the MAPK pathway.
Clinical: Bone pain in the distral extremities. Other symptoms depend on site involved. May be totally asymptomatic or lethal (wide range).
Serology: Unique cytokine profile of high IFN-a, IL-12, MCP-1, and low IL-4 and IL-7.
Histology: Infiltrate of bland-apperaing foamy histiocytes with surrounding fibrosis. Touton giant cells are often present.
Hemophagocytic lymphohistiocytosis
May be familial or sporadic
Familial form is an autosomal recessive progressive disease starting from a young age. There is decreased NK cell function. Mutations are often in perforin. Acquired form is often associated with some immunodeficiency and may be triggered by infection, malignancy, GVHD, or HELLP.
Generally caused by a failure of NK cells to elimiate targets of anitenicity and ensuing immune frustration.
Clinical: Sudden onset SIRS with accompanying cytopenias, hepatosplenomegaly, and lymphadenopathy. Jaundice and rash may be present.
Histologic: Hemophagocytosis of all blood lineages.
Features that distinguish reactive from malignant marrow histiocytosis
- Pleomorphism of macrophages
- Features of atypia and immaturity
- Prominent nucleolus
- Dinstict, thick membrane
- Irregular nuclear chromatin
- Multinuclearity
- Presence of monoblasts and promonocytes among clusters of macrophages (shown)
Immunohistochemical / flow cytometry features of M0/MΦ
- CD68 positivity (macrosialin, not totally specific)
- CD163 positivity (quite specific for M0/MΦ)
Genetic etiologies of familial HLH
- Perforin loss-of-function or deletion (PRF1)
- SH2D1A (SAP) mutation, aka SLAM-associated protein. Acts as an adaptor for Fyn and thus promotes tyrosine kinase activity.
- UNC13D mutation (encodes MUNC13-4, which is vital for cytolytic granule fusion)
- STX11 mutation (member of the t-SNARE family, also associated with vesicle fusion).
Chediak-Higashi syndrome
Autosomal recessive disorder
Homozygous LoF in the Lyosomal trafficking regulator (LYST) gene.
Defect in microtubule polymerization and chemotaxis of neutrophils, ultimately resulting in defective phagosome-lysosome fusion.
Clinically characterized by recurrent pyogenic infections, partial albinism, peripheral neuropathy, and HLH.
Histologically associated with giant cytoplasmic granules in granulocytes and platelets, often with pancytopenia.
Treatment is HSC transplant.
Griscelli syndrome
Autosomal recessive
Three “types” with different genetic origins and clinical manifestations:
- Type 1: Myosin Va mutation (Ch 15q21). Silver-gray hair and neurologic abnormalities. Developmental delay, hypotonia, seizures. Supportive care.
- Type 2: Rab27a mutation (Ch15q21). Silver-gray hair and immunodeficiency. Predisposed to HLH and hypogammaglobulinemia. Treat with HSC transplant.
- Type 3: MLPH mutation (2q37.3), F exon of Myosin Va. No neurologic or immunologic abnormalities. Cosmetic issue only, no treatment necessary.
Microscopically, all types demonstrate large clumps of pigment distributed irregularly along the hair shaft on hair microscopy. Biologically, the problem is that the pigment cannot be distributed due to the defective actin-myosin-Rab system.
Tons of these cells are seen in the blood and marrow of a kid with failure to thrive. What is the diagnosis?
Some form of lysosomal or mucopolysaccharide storage disease.
This particular image is from a child with Niemann Pick.
Signs of neutrophil hyperactivation
Toxic granulation
Dohle bodies (remnant of rough ER, not much is known about formation)
This is seen on Romanowsky stain in bone marrow. What is the diagnosis?
Whipple’s disease
Whipple’s can also be seen in the bone marrow!
T. whipplei characteristically stains violet on Romanowsky stain, blue on AB/PAS, and black on silver stain.
What is going on in this Giemsa-stained bone marrow smear?
Leishmaniasis/Kala azar
These are macrophages containing Leishman-Donovan bodies in a patient with Kala azar.
Each parasite has an ovoid nucleus with a smaller rod-like kinetoplast at a right-angle to the nucleus. Features of dyserythropoiesis may also occur in the setting of kala azar.
Recitulin fibrosis and gelatinous transformation in AIDS
AIDS marrow disease may involve destruction of bone marrow, starting as marrow fibrosis with reticulin fibers and progressing to replacement of marrow with an amorphous, eosinophilic-to-deep blue, mucinous material (shown).
Gelatinous marrow is composed of hyaluronic acid and glycosaminoglycans with admixed dead fat cells and sparse cellular marrow elements. This stage of marrow disease is usually assoicated with trilineage dysplasia.
What’s going on in the marrow of this AIDS patient?
Cryptococcal infection of the bone marrow
It can also be appreciated on PAS stain (shown) and silver stain.
What’s going on in this Romanowsky stained bone marrow?
This patient has some mycobacterial infection.
These are mycobacterial “ghosts” within macrophages.
May be due to M. leprae or atypical mycobacteria – not typically TB.
Sea blue histiocyte syndrome
Group of inherited disorders in which large macrophages containing coarse ganules that stain sea blue on Romanowsky are seen in the marrow, liver, spleen, and other organs. May occur secondarily to heritable lipid storage disorders.
May also be acquired in rare cases of myeloproliferative syndromes, Hodgkin’s lymphoma, rheumatoid arthritis, and autoimmune TTP.
This staining is due to the presence of ceroid, a molecule histochemically similar to lipofuscin.
What’s going on in this patient’s marrow?
Amyloidosis
Note the amorphous, acellular pink material.
Usually associated with light-chain producing myelomas (primary amyloidosis), however may be seen in secondary amyloidosis in the setting of chronic inflammation.
Post-mortem bone marrow changes
- Progressive cellular vacuolation
- Appearance of nucleolus-like nuclear inclusions
- Dumbell-shaped nuclei and nuclear lobulation
- Karyorrhexis and karyolysis
