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Chapter 34 METASTASES OF SOLID TUMORS
In solid tumors
tumors
bone marrow (BM) is is usually evaluated for one one of of the following: staging at at at at diagnosis (especially in in in in in in in some some types of of adult cancer and and in in in in in in in pediatric small round cell tumors) to assess treatment response and and iden fy relapse Marrow involvement is is is is generally found in in in in in in in disseminate neoplasias with widespread metastases In some some cases however the diagnosis of solid neoplasia neoplasia is is is is based on on on on on a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a BM examina on on on on on performed for for par cular indica ons such as as as as as as as bone bone pain pathological fractures increased increased uptake at at at bone bone scin graphy or or or or or or abnormal radiological ndings hypercalcemia or or or or increased increased serum alkaline phosphatase or or or or unexplained changes in in in in in in in in in blood count (Bain et et al al al al al al al al 2010) Bone marrow marrow metastases from non-hematopoie c c c c c c c c c c c neoplasia are usually associated with a a a a a a a a a a a a a a a a a a a a a a a a a a a a leukoerythroblas c c c c c c c c c c c blood blood picture i i i i i i i i i i i i i e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e e the the the the presence of of immature red and/or white cells in in the the the the peripheral blood blood Tumor marrow marrow marrow in in ltra- on on disturbs the the the the the marrow marrow microvasculature and and and allows early release of of of the the the the the precursors Generally leukoerythrobla- s s s s s s s s s s s s s s s s s c c c c c c c c c c c c c c c c c anemia anemia correlates with with the the the degree of of of reac ve brosis It can also occur in associa on on on on with with re re re re re re re re re culocytosis and and red cell fragmenta on on on as a a a a a a a a a a a a a a a a a a re re re re re re ec on on on of of of microangiopathic hemoly c c c c c c c c c c c c c anemia anemia The extension of of of BM involvement varies from small foci to to to total replacement of of of the the hemopoie c c c c c c c c c c c elements Ne- oplas c c c c c c c c c c c c c c c cells cells cells cells may show features iden cal to to to to the the primary lesion or or or more or or or less di di eren ated whereas surrounding residual hematopoie c c c c c c c c c c c c c c c c c cells cells cells cells cells present non-speci c c c c c c c c c c c c c c c c c altera ons An increase increase of reac ve ve cells cells cells cells cells such as as as as as as as plasma cells cells cells cells cells mast cells cells cells cells macrophages or or increased iron stores may be be observed The The bone trabeculae are altered due to to to incre- ased ased osteoclas c c c c c c c c c c c c c c c c ac ac ac vity and osteoblas c c c c c c c c c c c c c c c c reac ons The The degree of brosis brosis is is is is variable: modest increase increase in in in in in in re re re re re re re re re re re culin bers surrounding neoplas c c c c c c c c c c c c cell clusters or or or di di di use use collagenous brosis brosis Moreover there is is is is is usually also par al al al or or or di di use necrosis Bone marrow trephine biopsy especially if performed bilaterally is is is a a a a a a a a a a a a a a a a a more sensi ve ve technique than BM BM aspirate to to to evaluate the the the presence of of BM BM metastases as as as as as as as well as as as as as as as to to to iden fy the the the histological subtype of of the the the neoplasia however aspirate aspirate and trephine biopsy biopsy are are indeed complementary techniques that should be performed simultaneously Oc- casionally neoplas c c c c c c c c c c cells are are observed on on on on aspirate aspirate smears but not on on on on biopsy biopsy sec ons Table 1 provides a a a a a a a a a a a a a a a a a a a a a summary of of the cytological aspects of of BM metastases Table 1 ytological features of bone marrow metastases from non hematopoie c c c malignancies                   Cell arrangement in in agglomerates
Polymorphism of of individual cell sizes
Heterogeneity of of nuclear size size chroma n n n n n n n structure dye a a a a a nity
Giant nucleoli
Frequent mul polar mitosis
Polychromasia of the cytoplasm that is is o o o o o o o o o o o o en en en not homogeneous nor well delimited
Bone marrow aspirate prepara ons are are are are usually of of of of poor quality because of of of of brosis osteosclerosis or or necrosis and and the the the iden ca ca ca ca on on on on on of of of of of rare metasta c c c c c c c c c c c c c c c c cells cells in in in the the the context of of of of of sclero sclero c c c c c c c c c c c c c c c c areas may require a a a a a a a a a a a a a a a a a a a a a a a a a a a very careful and and me me me me me cu- lous search Small clusters of of of of of neoplas neoplas neoplas c c c c c c c c c c c c c c c c c c cells cells cells cells are are are are are some mes observed in in in in one or two smears whereas in in in in other cases the the the the the neoplas neoplas neoplas c c c c c c c c c c c cells cells cells represent the the the the the dominant cell cell cell cell popula on on Clusters of of of of neoplas neoplas neoplas c c c c c c c c c c c cells cells cells of of of of di erent sizes
are are usually localized in in in the the the the tail or edges of the the the the smear Marrow in in in in in in in ltra on on on is most commonly observed at at onset in in in in in in in breast cancer in in in in in in in females (incidence of of of marrow me- tastases 27-35%) and and and and in in in in in in in in prostate and and and and lung malignancies in in in in in in in in males males (13-20% and and and and 5-21% of of of cases respec vely) but it can occur also in in in in in in tumors
of of the the thyroid kidney gastrointes nal tract pancreas ovary tes tes s s s s s s s s s s s s s s s s s s s s s s s s s s and and and and and melanoma Other neoplasms very rarely involve BM BM BM metastases metastases and and only in in in in in in in in advanced stages In childhood neuroblastoma presents with BM BM BM in in in in in in in ltra on on on in in in in in in in 50-60% of of cases High incidence of of BM BM BM metastases metastases is also observed at the the onset in in in in in in in other childhood neoplasms such as as as as as as as as as as rhabdomyosarcoma (15-20%) Ewing s s s s s s s s s s s s s s s s s s s s s s s s s s sarcoma sarcoma sarcoma sarcoma (13-36%) re re noblastoma (23-50%) and and ganglioneuroblastoma whereas osteosarcomas brosarcomas and and various types of of carcinoma only invade the the marrow marrow at at a a a a a a a a a a a a a a a a later stage of the disease course Bone marrow marrow metastases from from solid neoplasms should be di di eren ated from from various hematologic malignancies: high-grade non-Hodgkin lymphoma acute acute acute lymphoblas c c c c c c c c c c c leukemia leukemia (especially in in children) acute acute acute megakaryoblas c c c c c c c c c c c leukemia leukemia or or acute acute acute panmyelosis with brosis The study of of of an an gen expression by immunocyto-histochemistry plays a a a a a a a a a a a a a a a a a a a a a a a fundamental role in in the the the the di di eren al al al diagnosis Also the the the the iden ca ca on on of of of the the the the site of of of origin when the the the the primary neoplasm is unknown can be a a a a a challenge Reference
Bain BJ Clark DM Wilkins BS Bone marrow pathology (4th edi on) Wiley-Blackwell: Hoboken nited States 2010 p p 549-586 261






















































































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