Nonhematolymphoid tumors occasionally present with overt peripheral blood disease resembling acute leukemia (Table 28.1) (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19). Although often used, the terms “carcinoma cell leukemia” and “carcinocythemia” are not always appropriate because not all cases are attributable to carcinoma.

Leukemia may be the first sign of malignancy but is more often a terminal event, presaging death within days.

Flow cytometry shows no expression of myeloid or lymphoid antigens, with rare exception. Ewing sarcoma and related tumors express CD99 but not CD45 (14). Neuroblastoma expresses CD56 and, in some cases, CD117 but not CD45 (15,16).

The peripheral blood shows numerous bizarre cells, often showing coarse chromatin, prominent nucleoli, and basophilic cytoplasm. Auer rods and myelodysplastic changes are absent. The bone marrow aspirate and core biopsy sections typically show massive replacement by malignant cells.

The differential diagnosis includes acute leukemia, the leukemic phase of malignant lymphoma, and non-malignant cells rarely seen in the peripheral blood, including endothelial cells, osteoclasts, trophoblasts, Gaucher cells, and mast cells (Figs. 28.1 and 28.2) (1,17). Leukemic rhabdomyosarcoma can be particularly difficult to diagnose correctly because many cases show no evidence of a primary site, but only peripheral blood and bone marrow disease. Immunostains, immunophenotyping by flow cytometry, electron microscopy, and’or genetic studies may be both useful and misleading. The correct diagnosis has often made only at autopsy.

It should be kept in mind that small round cell tumors, such as Ewing sarcoma and neuroblastoma, may coexist with acute leukemia (18,19).

Nonhematolymphoid tumors in the bone marrow are occasionally primary but more often represent metastatic disease (Table 28.2)

Primary tumors reported in the bone marrow include fibromyxoma, fibrosarcoma, Kaposi sarcoma, and an indolent neuroendocrine tumor (20, 21, 22, 23, 24). It is also possible that some cases of Ewing sarcoma and rhabdomyosarcoma arise in the bone marrow.

Secondary or metastatic tumors are more often seen in the bone marrow. They are found with variable frequency, depending on the type of tumor and diagnostic method employed.

Metastatic carcinoma is detected in approximately 20% of bone marrow specimens obtained for staging with hematoxylin-and-eosin staining; its presence is a poor prognostic sign (25, 26, 27, 28, 29, 30, 31, 32, 33, 34). Tumor cells are detected in more than 50% of peripheral blood and bone marrow specimens obtained for staging and studied by immunologic and molecular methods; their presence is of uncertain prognostic import. Metastatic carcinomas found in the bone marrow usually originate in the breast, prostate, lung, or gastrointestinal tract. Less common sites include the kidney, thyroid, skin, and pharynx.

Metastatic malignant melanoma also occurs in the bone marrow (35,36). The primary site may be undetectable.

Metastatic sarcomas, small round cell tumors, and brain tumors may metastasize to the bone marrow (37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66). These include angiosarcoma, desmoplastic round cell tumor, esthesioneuroblastoma, Ewing sarcoma and related tumors, glioma and glioblastoma multiforme, liposarcoma, malignant rhabdoid tumor, medulloblastoma, neuroblastoma, oligodendroglioma, pineoblastoma, primitive neuroectodermal tumor, retinoblastoma, and rhabdomyosarcoma, including alveolar, clear cell, embryonal, and pleomorphic variants. Metastatic Kaposi sarcoma and leiomyosarcoma have been reported in the bone marrow of patients infected by human immunodeficiency virus type 1. Metastatic neuroblastoma usually occurs in children, even as young as neonates. Osteosarcoma may involve the bone marrow by direct extension or metastasis. In bone marrow involvement by rhabdomyosarcoma, a primary site is frequently not found, suggesting the possibility that some cases may be primary tumors of the bone marrow. A primary origin in bone marrow is likely in at least some cases of Ewing sarcoma (22).