Page 6 - Illustrated Pathology of the Bone Marrow

Fibrosis 129
usually do not show perinuclear cytoplasmic clearing, and
demonstrate Auer rods that are not present in reactive
promyelocytes. A repeat bone marrow examination one to
two weeks after cessation of the growth factor will usually
demonstrate more complete granulocyte maturation, and
such a study is advisable in cases that are worrisome for
residual leukemia. If true leukemic blast cells are present,
they will persist or increase during this brief time interval,
while reactive growth factor changes will resolve with time.
Less common changes that have been reported after G-
CSF and GM-CSF therapy include marrow fibrosis (Orazi
et al., 1992), marrow necrosis (Katayama et al., 1998), and
marrow histiocyte proliferations (Wilson et al., 1993), which
may be confused with metastatic tumors (Pekarske & Shin,
1996).
Granulomas
The immunodeficiency associated with chemotherapy also
increases these patients’ risk for infectious diseases. Exam-
ination of the bone marrow is one means of evaluating
patients for infections. If an infectious disease is suspected, stains for organisms should be performed, especially when
fresh bone marrow aspirate material should be sent for
microbiology studies. Histochemical stains for acid-fast
and fungal organisms should be performed on all post-
therapy biopsy specimens containing granulomas.
Necrosis
Bone marrow necrosis is a relatively uncommon find-
ing, although the exact incidence is variable in the lit-
erature (Janssens et al., 2000; Paydas et al., 2002). When
present, however, it is most commonly associated with mar-
row involvement by malignancy, and less frequently with
infections, drug therapy, sickle cell disease, or other sys-
temic abnormalities. The malignancies most often associ-
ated with marrow necrosis are acute leukemias, especially
acute lymphoblastic leukemia, high-grade non-Hodgkin
lymphomas, Hodgkin lymphoma, and metastatic carci-
noma. Bone marrow necrosis may also be observed after
chemotherapy. Bone marrow necrosis unrelated to anti-
neoplastic therapy is discussed in Chapter 6.
Although not well studied, acute leukemias with mar-
row necrosis present prior to therapy appear to show
post-therapy necrosis more commonly than specimens
from patients that had non-necrotic pre-therapy speci-
mens. Post-therapy necrosis usually shows complete mar-
row replacement by non-viable “ghost cells” with pyknotic
nuclei and degenerative cytoplasm (Fig. 14.7). A careful
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AB
Figure 14.7. (A) Post-therapy necrosis. (B) Note the “ghosts” of
blast cells in this case of acute myeloid leukemia.
examination should be performed to exclude the possibil-
ity of foci of viable residual tumor in these patients. Samples
obtained in the course of or soon after therapy may entirely
consist of large acellular areas of fibrinous, eosinophilic,
necrotic material. Later, necrotic areas may be bordered by
regenerating hematopoietic tissue. Areas of necrosis may
be replaced by normal regenerating elements on follow-up
specimens or may be replaced by fibrosis in subsequent
biopsies. Post-therapy bone marrow necrosis caused by
specific drugs is even less common, but has been reported
with α-interferon, all-trans-retinoic acid, fludaribine, and
G-CSF (Dreosti et al., 1994; Katayama et al., 1998; Janssens
et al., 2000).
Patients that have undergone prior therapy are also at
high risk for infections, and infectious causes of marrow
necrosis must also be considered in these patients. Special
focal areas of necrosis are present in the marrow, even in the
absence of granulomatous inflammation. If special stains
are negative for organisms, repeat bone marrow aspiration
for bacterial, fungal, or viral cultures should be considered if
unsuspected necrotic foci are found that are not associated
with necrotic tumor.
Fibrosis
Except for the development of fibrosis as part of the resolu-
tion of marrow necrosis, as mentioned previously, marrow
fibrosis usually decreases or disappears after treatment of
the primary disease by either chemotherapy or hematopoi-
etic stem cell transplantation (Islam et al., 1984). Devel-
opment of marrow fibrosis after therapy may represent