Dardick I, Caldwell D R, Moher D, Jabi M
Department of Laboratory Medicine, Ottawa Civic Hospital, Ontario.
Hum Pathol. 1988 Aug;19(8):889-901. doi: 10.1016/s0046-8177(88)80003-0.
Twelve examples of mixed small- and large-cell lymphoma (eight follicular, one follicular and diffuse, and three diffuse) were investigated morphometrically using plastic-embedded tissue in order to study nuclear characteristics of lymphocyte populations in this form of non-Hodgkin's lymphoma (NHL) and to test morphologic bases for current NHL classification systems. This study illustrates that there are many inaccuracies, illusions, and misconceptions in the morphologic criteria currently used to classify mixed small- and large-cell lymphoma. A principal finding was that lymphocyte nuclear profiles in mixed-cell lymphomas tend to be smaller in size (P less than .005) and more irregular in shape (P = .0001) than the morphologically similar counterparts in germinal centers of lymph nodes with reactive hyperplasia. Intercase comparison of mixed small- and large-cell lymphomas revealed a considerable range of mean nuclear area values, some of which were within the size range of normal, small lymphocytes. At the magnifications used for morphometric assessment, a high proportion of lymphocyte nuclear profiles had shallow invaginations, but only a limited number of profiles (4% to 14%) had deep (cleaved) indentations. Contrary to current definitions for this subtype of NHL, lymphocytes with "small" nuclei had the same proportion of the nuclear diameter occupied by nuclear invaginations as lymphocytes with "large" nuclei and, in fact, mean nuclear invagination depth was shallower in "small" nuclei than in "large" nuclei. Furthermore, regardless of whether it is nuclear area or shape that is evaluated, lymphocytes in mixed-cell lymphoma do not separate into two populations of small-cleaved and large noncleaved cells. Morphometry reveals that only four of the 12 examples of mixed small- and large-cell lymphoma had a proportion of the lymphocytes in the size range of fully transformed germinal center lymphocytes that exceeded 25%, and none of the cases approached 50% even though the population of lymphocyte nuclei appearing "transformed," and therefore "large," ranged from 28% to 57%. Such results indicate that the large, noncleaved and cleaved component, as seen in histologic sections of mixed small- and large-cell lymphoma, do not have nuclei of uniform size and many, in fact, are not actually large. The morphometric findings indicate reasons for the poor observer reproducibility in classifying this subtype of NHL.
对12例混合性小细胞和大细胞淋巴瘤（8例滤泡性、1例滤泡性和弥漫性、3例弥漫性）进行了形态计量学研究，采用塑料包埋组织，以研究这种非霍奇金淋巴瘤（NHL）中淋巴细胞群体的核特征，并检验当前NHL分类系统的形态学基础。本研究表明，目前用于分类混合性小细胞和大细胞淋巴瘤的形态学标准存在许多不准确、错觉和误解。一个主要发现是，与反应性增生的淋巴结生发中心形态学相似的对应细胞相比，混合细胞淋巴瘤中的淋巴细胞核轮廓在大小上往往较小（P<0.005）且形状更不规则（P = 0.0001）。混合性小细胞和大细胞淋巴瘤的病例间比较显示平均核面积值范围相当大，其中一些在正常小淋巴细胞的大小范围内。在用于形态计量评估的放大倍数下，高比例的淋巴细胞核轮廓有浅凹陷，但只有有限数量的轮廓（4%至14%）有深（裂开）凹陷。与目前对这种NHL亚型的定义相反，“小”核淋巴细胞的核凹陷占核直径的比例与“大”核淋巴细胞相同，实际上，“小”核的平均核凹陷深度比“大”核浅。此外，无论评估的是核面积还是形状，混合细胞淋巴瘤中的淋巴细胞都不会分成小裂细胞和大无裂细胞两个群体。形态计量学显示，12例混合性小细胞和大细胞淋巴瘤中只有4例的淋巴细胞比例在完全转化的生发中心淋巴细胞大小范围内超过25%，即使出现“转化”因此“大”的淋巴细胞核群体范围为28%至57%，也没有病例接近50%。这些结果表明，在混合性小细胞和大细胞淋巴瘤的组织学切片中看到的大无裂和裂细胞成分没有均匀大小的核，实际上许多并非真正的大核。形态计量学结果表明了在对这种NHL亚型进行分类时观察者再现性差的原因。
