Histopathology in Prognosis 4r Therapy of Lymphocytic Lymphomas 249 



there any evidence, once significant interference with marrow function had 

 occurred by virtue of replacement by lymphatic tissue, that cytocidal therapy 

 induced a regeneration of myeloid tissue even if the amount of lymphatic- 

 tissue decreased. Rather, severe serous fat atrophy leading to disability and 

 death from pancytopenia developed (Fig. 17-11). As a result evaluation o\ 

 marrow histology with respect to the adequacy of the myeloid tissue was 

 an important aspect in management. Progressively extensive replacement 

 of myeloid tissue indicated a decreasingly poorer response to therapy and a 

 poorer prognosis. Progressive serous atrophy, part of the natural history of 

 the diseases which was aggravated by treatment, has had a similar signifi- 

 cance. 



Since the introduction of radiation and chemotherapy, the "laws" of 

 Beroonie and Trihondeau have dominated our thinking. 13 These authors 

 originated the concept that immature, rapidly dividing cells were most 

 sensitive to irradiation. Examination of their data indicated that their laws 

 were based upon observations made on the testis of one rabbit. 14 On the 

 other hand, starting with Heineke's-* experiments, there have been numer- 

 ous studies to indicate that these laws are invalid. 1 -' 13 > 15 Similarly, parallel- 

 ing our faith in these laws, but again lacking any verification, there has been 

 tacit acceptance of the belief that malignant cells were more sensitive to 

 irradiation than corresponding nonmalignant cells. However, serial biopsy 

 of tissues of patients with malignant diseases of the hematopoietic tissues has 

 effectively disproved this concept. 13, 28 Case 9 illustrated what happened to 

 the marrow when an attempt was made to "burn out" the malignancy. One 

 must anticipate damage to myeloid tissues as well as to the lymphatic tissues 

 when a patient with a lymphatic malignancy is treated with isotopes or 

 with chemotherapy. The degree of anemia, thrombopenia, or neutropenia 

 following treatment depended on the amount of myeloid tissues present 

 prior to treatment and the dose and duration of treatment. 9 ' 14 As the 

 amount of myeloid tissue decreased, whether because of atrophy or replace- 

 ment, the patient was more likely to develop pancytopenia of serious 

 degree following treatment. Conversely, the more active the myeloid tissue, 

 the more likely the patient was to withstand the cytocidal effect of treatment 

 and to obain a remission. 



The situation became more complicated because hyperplasia was often an 

 evidence of a complicating factor such as abnormal destruction of red 

 cells, white cells, and platelets. Frequently the hypersplenic syndrome w'as 

 a more serious problem than other aspects of the lymphomatous disease. 

 Evaluation of the role of the marrow is predicated upon the availability of 

 sections of a suitable biopsy specimen. Smears of aspirated marrow were 

 unreliable for the purpose outlined. 



With some practice one may estimate the adequacy of the marrow from 



