METASTATIC MALIGNANCY FROM UNKNOWN PRIMARY SOURCE
In most series, a primary site of origin for the metastatic malignancy is identified in only 15% of the
cases prior to death. Whether a primary site is identified or not, survival usually is short with a median
of 6 months. There is considerable variation in the incidence of bone marrow metastasis for various types
of malignancies. Some of the most common neoplasms also have the highest incidence of marrow involvement.
These include carcinomas of the breast (up to 20%), prostate (13-20%), lung (SCC, 3-15%; adenocarcinoma, 5
to 10%) and gastrointestinal tract (4%; mostly stomach and colon) in adults; and neuroblastomas (50-60%) in
children. The variability in the reported incidence for these tumors may reflect differences in patient
selection as well as in techniques used to identify metastatic involvement in the bone marrow. In our
experience with neuroblastoma, a combined approach in which aspirate smears, touch preparations, bone marrow
particle sections, and bilateral bone marrow biopsy are simultaneously obtained seems capable of providing
the highest tumor yield.
Metastatic involvement of the bone marrow may be focal or diffuse. In osteolytic tumors the bone trabeculae
show erosion and osteopenia. In the less common osteoblastic lesions (usually prostate and breast
adenocarcinoma), irregular thickening of the bone trabeculae is usually observed. Selected antibodies which
we find useful for the characterization of metastatic tumors in bone marrow are listed in.
- Brunning Richard D, McKenna Robert W. Tumors of the Bone Marrow. Atlas of Tumor Pathology 1994;9:457.
- Lagendijk JH, Mullink H, Van Diest PJ, Meijer GA, Meijer CJ. Tracing the origin of adenocarcinomas with
unknown primary using immunohistochemistry: differential diagnosis between colonic and ovarian carcinomas
as primary sites. Hum Pathol 1998;29:491-7.
- Lazda EJ, Berry PJ. Bone Marrow Metastasis in Ewing's Sarcoma and Peripheral Primitive Neuroectodermal
Tumor: An Immunohistochemical Study. Pediatric and Developmental Pathology 1998;1:125-30.
- Maeda T, Kajiyama K, Adachi E, Takenaka K. Sugimachi K, Tsuneyoshi M. The expression of cytokeratins 7, 19,
and 20 in primary and metastic carcinomas of the liver. Mod Pathol 1996;9:901-9.
- Mansi JL, Berger U, Wilson P, Shearer R, Coombes RC. Detection of tumor cells in bone marrow of patients
with prostatic carcinoma by immunocytochemical techniques. J Urol 1998;139:545-8.
- Mathieu MC, Friedman S, Bosq J, Caillou B, Spielmann M, Travagli JP, Contesso G. Immunohistochemical
staining of bone marrow biopsies for detection of occult metastasis in breast cancer. Breast Cancer Res
- Moll R, Lowe A, Laufer J, Franke WW. Cytokeratin 20 in human carcinomas. A new histodiagnostic marker
detected by monoclonal antibodies. Am J Pathol 1992;140:427-47.
- Ramaekers F, van Niekerk C, Poels L, Schaafsma E, Huijsmans A, Robben H, Schaart G, Vooijs P. Use of
monoclonal antibodies to keratin 7 in the differential diagnosis of adenocarcinomas. Am J Pathol
- Riopel M, Dickman PS, Link MP, Perlman EJ. MIC2 analysis in pediatric lymphomas and leukemias. Hum Pathol
- Robertson PB, Neiman RS, Worapongpaiboon S, John K, Orazi A. 013 (CD99) positivity in hematologic
proliferations correlates with TdT positivity. Mod Pathol 1997;10:277-82.
- Soslow RA, Bhargava V, Warnke RA. MIC2, TdT, bcl-2, and CD34 expression in paraffin-embedded high-grade
lymphoma/acute lymphoblastic leukemia distinguishes between distinct clinicopathologic entities. Hum Pathol
- ten Velde GP, Kuypers-Engelen BT, Volovics A, Bosman FT. Examination of bone marrow biopsy specimens and
staging of small cell lung cancer. Eur J Cancer 1990;26:1142-5.