NON-NEOPLASTIC DISEASES
OF HEMATOPOETIC ORGANS
Pathology
Jan Żeromski
20010/2011
PATHOLOGY OF THYMUS
Developmental defects – aplasia (Di George anomaly),
Nezelof syndrome
Follicular hyperplasia with germinal center formation (myasthenia
– in 70% of cases,SLE, Graves disease)
Thymic tumors:
1. Thymomas - tumors of thymic epithelial cells
- Benign-mostly of medullary epithelial cells
- Malignant
a) Type I - cytologically benign but biologically aggressive
(mainly of cortical epthelial cells)
b) Type II - „thymic carcinoma”- 5% of thymomas
2. Lymphomas ( of T cell) Hodgkin’ disease
3. Others ( carcinoids, teratomas etc.)
PATHOLOGY OF LYMPH NODES (LN)
Lack or hypoplasia of LN cortex - in immunodefic.
Atrophy - in old age, after irradiation,
chemotherapy
Inflammations - acute, chronic, non-specific,
specific
Enlargement due to storage of various
compounds
Tumors:
 Primary
- lymphomas
 Secondary - carcinomas (metastases)
CHRONIC NON SPECIFIC
LYMPHADENITIS
Follicular hyperplasia:
caused by infection with microbes activating
B cells.
Paracotical lymphoid hyperplasia:
due to infection with microbes activating T cells.
Sinus histiocytosis:
accumulation of histiocytes in lymphatic
sinusoids. Occurs in LNs draining cancers
(of breast and/or stomach).
Hyperplasia follicularis
Hyperplasia follicularis
CHRONIC „SPECIFIC’ LYMPHADENITIDES
Toxoplasmosis:
Small epithelioid cell granulomas, both T and B cell
are involved.
Cat scratch disease: (e.: small Gram neg. bacteria).
Enlargement and suppuration of LN after skin inc
ident such as cat scratch.
Lymphogranuloma venereum: (e.: Chlamydia)
Enlargement of LN, granuloma formation suppuration, liquefaction.
Mesenteric lymphonodulitis: (e.: Yersinia
pseudotuberculosa) - Granulomas with tendency to
necrosis of mesenteric LNs.
CHRONIC „SPECIFIC” LYMPHADENITIS 2
Tuberculosis: (e.: tubercle bacilli)
Necrotic granulomas
Tularemia: (e.: Francisella tularensis)
Focal necrotic lesions in LN and other organs
surrounded by monocytes, fibroblasts, lymphocytes
as in tbc.
Sarcoidosis:
Granulomas formed by mononuclear phagocytes
surrounded by a rim of T-helper cells and sometimes
B lymphocytes. They are due to cytokine release by Th.
Infectious mononucleosis: (e.EBV infection)
Activation of T area, immunoblast infiltrates, dispersed
light reticulum cells, sinuses widened with immunoblasts
and plasma cells.
Millary tuberculosis of the spleen
Typical epithelioid cell tubercles with Langhans` giant cells. HE, 100x
Tularemic lymphadenitis; margin of necrotic area
No caseation, though there are scattered areas of necrosis. Note epithelioid cell zone with
several Langhans` giant cells.
Lymphadenitis due to tularemia (Pasteurella tularensis)
Center: necrotic area surrounded by wide zone of epithelioid cells with a few Langhans`
giant cells. At the upper boundary of the central wedgeshaped area of necrosis there is
some nuclear debris. Diagnosis serologically confirmed. HE, 65x
Sarcoidosis of hilar lymph nodes
Epithelioid cell nodules without caseation; much fibrosis and abundant giant cells. Center:
an “asteroid body”. HE, 100x
OTHER LYMPHADENOPATHIES
Post vaccinal and viral lymphadenitis
LN draining the site of vaccination ( polio, tetanus,
pertussis, diphteria) and viral infections, (CMV,
influenza),
Hist. - diffuse hyperplasia and an increase of
immunoblasts.
Anticonvulsant drug lymphadenopathy (dilantin L.)
may happen after 1 week to many months after
therapy
Sympt. - skin rash, fever, hepatosplenomegaly,
painful joints.
OTHER LYMHADENOPATHIES 2
Dermatopathic L. (lipomelanotic reticulosis)
associated with chronic dermatosis esp. exfoliative type
Hist. - widened pale-stained T-zone areas with foaming vacuolated
macrophages with fat and/or melanin droplets.
Lymphadenitis following lymphangiography
due to accumulation of fat globules in LN sinuses
Whipple disease (e.Tropheryma whippelli Gram+ bact.)
accumulation of pale-staining, PAS+ macrophages loaded with
bacteria in small intestinal mucosa and sinuses of draining LN
clin.: malabsorption syndrome, polyarthritis,
lymphadenopathy,hyperpigmentation, psychiatric disorders
OTHER LYMPHADENOPATIES - 3
HIV-related lymphadenopathy (very large lymphoid
follicles with giant germinal centers, later fragmentation
and atrophy)
Lymphadenopathy in rheumatoid arthritis (enlargement
of lymphoid follicles, low proliferative activity of germinal
centers, accumulation of plasma cells between follicles,
infiltration of neutrophils in sinuses
Lymphadenopathy in infectious mononucleosis (in
paracortical area proliferation of immunoblasts – mostly
B cells, with high mitotic activity
VIRUS-ASSOCIATED HEMOPHAGOCYTIC
SYNDROME (VAHS)
Etiology: rare complication of viral infections (EBV,
CMV,adenoviruses, B19 parvovirus and other)
Incidence:
most often in renal transplant and/or immunosuppressed
patients
Clin.:
fever, pulmonary infiltrates, hepatospleno-megaly,
lymphadenopathy, cytopenia
Hist.:
LN enlarged, small lymphoid follicles without germinal
centers, with abundant nuclear debris, free or in
cytoplasm of proliferating histiocytes.
Prognosis: uncertain, potentially reversible
CASTLEMAN DISEASE
Two major gross types :
single localized – large tumor in mediastinum, non-specific symptoms:
fever, anemia, hypo-proteinemia, polyclonal
hipergammapathy;good prognosis
Multifocal – general lymphadenopathy,high fever, weight loss, skin
changes, hemolysis, poli- or mono-hypergammapathy, possible
progress to lymphoma; poor prognosis
Probable etiology: infection with herpes virus HHV-8
Histology – two types:
vascular hyaline - atrophy of germinal centers in lymphoid follicles,
numerous venules surrounded by hyaline masses (angiofollicular
lymph node hyperplasia)
(predominant in single localised type)
plasma cellular – interfollicular spaces filled with plasma cells
(predominant in multifocal type)
SPLEEN – MAJOR FUNCTIONS
Filtration of unwanted elements from blood – aged and
damaged cells, but also bacteria, cell debris,abnormal
metabolic molecules - phagocytic functions
Major secondary organ in the immune system- antibody
production, especially of IgM class
A source of lymphoreticular and hematopoetic cells
A reserve pool and storage site of blood cells
CAUSES OF SPLENOMEGALY
1.
2.
3.
4.
5.
6.
7.
Infections
Congestive states
Lymphohematologic disorders
Parasitic infestations
Connective tissue diseases
Storage diseases
Varia (amyloidosis, cysts, neoplasms etc.)
Splenomegaly associated with acute infection
(“septic spleen”)
Septicemia arising from liver abscesses due to echinococcosis. Spleen weight 610g.
Splenomegaly associated with acute infection
Hyperplasia of reticulum cells in red pulp. Note presence of large pulp cells separated from
their normal connection. Leucocyte infiltration, erythrophagocytosis. HE, 520x
Chronic splenomegaly in response to infection
Note active proliferation of reticulum cells, deployment of littoral cells, erythrophagocytosis.
HE, 520x
Hypersplenism – clinical features
Splenomegaly –dragging sensations in the
abdomen (left upper quadrant)
Discomfort after eating
Anemia, leukopenia
Thrombocytopenia
Hyperplasia of bone marrow precursors
Banti Syndrome –
Non-cirrhotic or Idiopathic Portal Hypertension
Etiology
After subclinical occlusion of the portal vein
Symptoms
Splenomegaly, hypersplenism, anemia
Hist.
Splenic red pulp replaced by fibrosis
deposition of collagen in basement membranes of
sinusoids impairs blood flow leading to excessive
destruction of blood cells.
Focal hemorrhages become organised with deposits
of hemosiderin and calcium (Gamna-Gandi bodies).
Treatment
surgical shunting procedures
LEUKOCYTOSIS
Granulocytosis (inflammations, tissue necroses)
Eosinophilia (allergy, parasitic infect., some skin
diseases)
Lymphocytosis (viral infections, severe chronic
infections)
Monocytosis (severe chronic bacterial/
fungal inf.)
Mastocytosis (increased numbers of mast cells
in skin and sometimes in other organs)
Leukemoid reaction (huge numbers of immature
cells in blood
LEUKOPENIA-USUALLY
GRANULOCYTOPENIA (BELOW 1000/c.mm)
Reduced production
Suppression of myeloid
stem cells
Neoplastic occupation
of bone marrow
Suppression of
granulocyte precursors
Vit. B12 or folate
deficiency
Accelerated removal
Hypersplenism
Inreased utilization-in
infections
Felty’s syndrome
Exposure to drugs
Proliferation of CD8+
LGL in bone marrow
Features Of Mononuclear Phagocyte System – MPS
(Reticulo - Endothelial Sys.)
Compounds:
Monocytes, macrophages, reticulum cells,
histiocytes, endothelia, dendritic cells.
Function:
a.
b.
c.
d.
e.
endocytosis (phagocytosis, pinocytosis)
storage and clearance
secretory activity
role in immune reactions
role in inflammation and infection
PROLIFERATIVE DISORDERS OF MPS
Localized (reactive or neoplastic)
Multicentric

reactive (Tbc, sarcoidosis)
 neoplastic (?)
Systemic

reactive (storage diseases, VAHS)
 neoplastic (malignant histiocytosis)
LANGERHANS’ CELL HISTIOCYTOSIS
(HISTIOCYTOSIS X) (1)
Unifocal: eosinophilic granuloma
Expanding erosive accumulation of
Langerhans’ cells (dendritic cells) admixed
with eosinophils, plasma cells, lymphocytes
within medullary cavities of bones.
Any bone may be involved, but commonly
ribs, calvarium, femur but also teeth.
LANGERHANS’ CELL (LC) HISTIOCYTOSIS
(HISTIOCYTOSIS X) (2)
Multifocal: Hand – Schuller - Christian dis.
Proliferation of mature Langerhans’ cells with abundant
intracytoplasmic lipids (cholesterol, its esters, neutral
fats)
Aberrant expression of chemokine receptors – CCR6
and CCR7 on LC – migration to tissues
Clin.: triad-bone lesions, exophtalmos, diabetes insipidus
(due tp involvement posterior stalk of the hypothalamus)
also - fever, skin eruptions, hepatospleno-megaly
Young children are affected,Prognosis fairly good
LANGERHANS’CELL HISTIOCYTOSIS
(HISTIOCYTOSIS X) (3)
Systemic: acute disseminated (Letterer - Siwe
disease
progressive proliferation of L. Cells leading to
destruction of hematopoesis, recurrent
infections and often to death,
Clin. - cutanous lesions, later involvement of
internal organs – hepatosplenomegaly,
lymphadenopathy,
Children before two years of age are affected.
Prognosis – poor
GAUCHER DISEASE
Pathogenesis:
Proliferation of histiocytes filled up with glucocerebroside
- lack of glucocerebrosidase, an enzyme needed to
hydrolize glycolipids from senescent blood cells
Gen.:
Mutation on chromosome 1 (q21-q31)
Symptoms:
Splenohepatomegaly (giant spleen up to 10 kg), erosion
of bones, anemia, leucopenia, various neuropathies
Hist.:
Infiltration of organs with Gaucher cells rich in
glucocerebrosides stored in lysosomes
Three types - adults (99%), infantile, juvenile.
NIEMANN-PICK DISEASE
Pathogenesis:


Accumulation of sphingomyelin in histiocytes (derived
from cell membranes, subcellular organelles, myelin
sheaths)
Lack of sphingomyelinase in two forms of N-P disease
Hist.: Foam cells in spleen, bone marrow, liver, lymph
nodes
Clin.: Hepatosplenomegaly, cachexia, mental
retardation
Two types: A - in infants (80%) and B - without
involvement of CNS
That’s all. You can relax!