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Electron microscopy in surgical pathology
CORRESPONDENCE
Clonality of Benign Lymphoid Proliferations
or therapeutic iinplications for the patient, several o f the examples cited by the attthors do not, in my opinion, substantiate a meaningfid role for electron microscopy. In tile examples presented in the Appendix on page 744, the electron microscopic demonstration o f secretory gramdes in a "pituitary adenoma known to be secreting prolactin" does not seem important for tile patient. Failure to show granules or glandular differentiation in a previously diagnosed squanmus carcinoma could support tile institution of treatment for non-small cell carcinoma, but it is notoriously difficult to confirm the absence o f something, given the problem o f sampling error. It is not clear that the demonstration of glands and granules in a subsequent example added anything to the treatment plan. On page 7-t5, is "Inetastatic carcinoum, st, ggestive o f primary renal cell carcinoma" (the electron microscopic diagnosis) a significant imt)rovement over "metastatic carcinoma, with hmg, kidney, an(l testis . . . possible primary sites" (tile light microscopic diagnosis)? Yet again, given that many treatment protocols differentiate only between small cell and rlOllsmall cell carcinoma o f hmg, is the patient benefitted by having electron microscopy change "poorly differentiated squamous carcinoma" to "poorly differentiated adenocarc i n o m a " ? A n d again, is " a d e n o s q u a m o u s c a r c i n o m a , suggestive o f primary lung carcinonm" therapeutically significantly different from the diagnosis made on the basis of light microscopy (example 3 on page 745)? My position is that these differences are riot significant. Furthermore, no data are provided that tile electron microscopic diagnosis proved, in fact, more accurate (in assigning primary site, for example) than the light microscopic diagnosis. For these reasons, I would considerably decrease the percentage o f cases in which electron microscopy played a role important enough to justify its expense. Since I do not have all o f the data, I cannot give an estimate, but the figure nlust be less than the 50 per cent put forward b)' the authors. However, even giving the data the most favorable interpretation and allowing that 50 per cent of electron microscopic examinations contributed to diagnosis, it is difficult to understand the authors' assertion that the procedure is underutilized. T o me, a procedure that in at least half o f cases contributes nothing is overq_tilized by a lot. 9 Finally, I believe that one issue, possibly addressed by the authors elsewhere, needs another look. I f 20 institutions did 290 electron microscopic studies in a month, then, on tire average, each did about 15 per month. Is this costeffective? Does it st,f flee to maintain technical and interpretive expertise? Could Stlch services be more centralized, especially in a system such as the VA? I wonder.
To the Editor:--The differential diagnosis of lymphoma and pset,dolymphom:i (atypical reactive hyperplasia) of the lung, as well as of other organs, presents a vexing problem. The contribution o f Herbert et al. x in a recent isst,e relied heavily on immunologic phenotyping and the assunq~tion that clonality necessarily separates malignant, neoplastic from benign, reactive conditions. It is widely recognized that virtually all lymphonms are monoclonal, with possible exceptions occurring in rare Epstein-Barr viral infections and in some patients who have undergone renal transplantation. T h e assumption that all monoclonal lymphocytic proliferations are lymphomas has been brought into question by a n n m b e r of studies, '2.s in which monoclonal polmlations of lymphocytes were found in histologically benign or atypical, reactive lesions. A similar approach, based on the assumed separation of malignant monoclonal and benign polyclonal lesions, has been taken by other investigatorsA .s Imnulnologic phenotyping must be interpreted in conjunction with morphologic and clinical findings in the evaluation o f borderline lesions. Until the significance of clonal proliferations of lymphocytes in borderline and benign lesions o f lymphocytes is clarified, such evaluations must be interpreted with caution. WI1.t.z:,t J. LUBBE, MD I)ivine Providence Hospital Williamsport, Pennsyh'ania 1. tterbert A, Wright DII, Isaacson PG, et al: Primary nudignant lymphoma of lung: histopathologicand immunologicevaluation of nine cases. HuM I'ATHOL15:415, 1984 2. Levy N. NelsonJ, Meyer P, et al: Reactivelymphoid hyl)erplasia with single class (monoclonal)surface immunoglobulin.Am J Clin Pathol 80:300, 1983 3. Turner RR, Egbert P, Warnke RA: 10"mt)hocytlcinfiltrate of the conjunctiva and orbit: imnnmohlstochemicalstaining of 16 cases. Ant J Clin Pathol 81:-t-t7, 198.1 4. Colby TV, Carrington BC: l'ulmonary lymphomas: ctirrent concepts. IluM PATIIOL1.t:88t, 1983 5. Kradin RL, Mark EJ: Benign lymphoid disordcrs of the lung, ~dth a theo D" regarding their development. Hu.~t PxrHot. 14:857, 1983
Electron Microscopy In Surgical Pathology To the Editor:'-LI would like to congratulate Doctors Williams and Uzmau on their painstaking analysis of diagnostic electron microscopy in surgical pathology (Hu.~t PATHOL 15:738, 1984), but I must take isstre with some of their collclusions. In these times of increasing ecouomic pressures, which cliallenge the VA system no less than others, it is essential that tests arid techniques be examined rigorously in terms of important benefit to patients. In light o f their prognostic
XVILLIAML. ~,VOLFSON, hiD Hoag Memorial Hospital Presbyterian Newport Beach, California
BOOK REVIEWS in Clinical Cytology, Volume 2, L. Koss and D. Coleman. New York, Masson, 1984. 314 pages, $69.50.
Advances
Tile editors have done a masterful job o f putting together this 12-chapter book covering a variety of recent
developments ill cytology. With 22 contributors, this is not a small feat. T h e book is a collection of articles ranging from practical concepts in cytology to more esoteric subjects that currently have little apparent clinical relevance. This observation is not meant as criticism but rather as a reflec-
650
Clonality of Benign Lymphoid Proliferations
or therapeutic iinplications for the patient, several o f the examples cited by the attthors do not, in my opinion, substantiate a meaningfid role for electron microscopy. In tile examples presented in the Appendix on page 744, the electron microscopic demonstration o f secretory gramdes in a "pituitary adenoma known to be secreting prolactin" does not seem important for tile patient. Failure to show granules or glandular differentiation in a previously diagnosed squanmus carcinoma could support tile institution of treatment for non-small cell carcinoma, but it is notoriously difficult to confirm the absence o f something, given the problem o f sampling error. It is not clear that the demonstration of glands and granules in a subsequent example added anything to the treatment plan. On page 7-t5, is "Inetastatic carcinoum, st, ggestive o f primary renal cell carcinoma" (the electron microscopic diagnosis) a significant imt)rovement over "metastatic carcinoma, with hmg, kidney, an(l testis . . . possible primary sites" (tile light microscopic diagnosis)? Yet again, given that many treatment protocols differentiate only between small cell and rlOllsmall cell carcinoma o f hmg, is the patient benefitted by having electron microscopy change "poorly differentiated squamous carcinoma" to "poorly differentiated adenocarc i n o m a " ? A n d again, is " a d e n o s q u a m o u s c a r c i n o m a , suggestive o f primary lung carcinonm" therapeutically significantly different from the diagnosis made on the basis of light microscopy (example 3 on page 745)? My position is that these differences are riot significant. Furthermore, no data are provided that tile electron microscopic diagnosis proved, in fact, more accurate (in assigning primary site, for example) than the light microscopic diagnosis. For these reasons, I would considerably decrease the percentage o f cases in which electron microscopy played a role important enough to justify its expense. Since I do not have all o f the data, I cannot give an estimate, but the figure nlust be less than the 50 per cent put forward b)' the authors. However, even giving the data the most favorable interpretation and allowing that 50 per cent of electron microscopic examinations contributed to diagnosis, it is difficult to understand the authors' assertion that the procedure is underutilized. T o me, a procedure that in at least half o f cases contributes nothing is overq_tilized by a lot. 9 Finally, I believe that one issue, possibly addressed by the authors elsewhere, needs another look. I f 20 institutions did 290 electron microscopic studies in a month, then, on tire average, each did about 15 per month. Is this costeffective? Does it st,f flee to maintain technical and interpretive expertise? Could Stlch services be more centralized, especially in a system such as the VA? I wonder.
To the Editor:--The differential diagnosis of lymphoma and pset,dolymphom:i (atypical reactive hyperplasia) of the lung, as well as of other organs, presents a vexing problem. The contribution o f Herbert et al. x in a recent isst,e relied heavily on immunologic phenotyping and the assunq~tion that clonality necessarily separates malignant, neoplastic from benign, reactive conditions. It is widely recognized that virtually all lymphonms are monoclonal, with possible exceptions occurring in rare Epstein-Barr viral infections and in some patients who have undergone renal transplantation. T h e assumption that all monoclonal lymphocytic proliferations are lymphomas has been brought into question by a n n m b e r of studies, '2.s in which monoclonal polmlations of lymphocytes were found in histologically benign or atypical, reactive lesions. A similar approach, based on the assumed separation of malignant monoclonal and benign polyclonal lesions, has been taken by other investigatorsA .s Imnulnologic phenotyping must be interpreted in conjunction with morphologic and clinical findings in the evaluation o f borderline lesions. Until the significance of clonal proliferations of lymphocytes in borderline and benign lesions o f lymphocytes is clarified, such evaluations must be interpreted with caution. WI1.t.z:,t J. LUBBE, MD I)ivine Providence Hospital Williamsport, Pennsyh'ania 1. tterbert A, Wright DII, Isaacson PG, et al: Primary nudignant lymphoma of lung: histopathologicand immunologicevaluation of nine cases. HuM I'ATHOL15:415, 1984 2. Levy N. NelsonJ, Meyer P, et al: Reactivelymphoid hyl)erplasia with single class (monoclonal)surface immunoglobulin.Am J Clin Pathol 80:300, 1983 3. Turner RR, Egbert P, Warnke RA: 10"mt)hocytlcinfiltrate of the conjunctiva and orbit: imnnmohlstochemicalstaining of 16 cases. Ant J Clin Pathol 81:-t-t7, 198.1 4. Colby TV, Carrington BC: l'ulmonary lymphomas: ctirrent concepts. IluM PATIIOL1.t:88t, 1983 5. Kradin RL, Mark EJ: Benign lymphoid disordcrs of the lung, ~dth a theo D" regarding their development. Hu.~t PxrHot. 14:857, 1983
Electron Microscopy In Surgical Pathology To the Editor:'-LI would like to congratulate Doctors Williams and Uzmau on their painstaking analysis of diagnostic electron microscopy in surgical pathology (Hu.~t PATHOL 15:738, 1984), but I must take isstre with some of their collclusions. In these times of increasing ecouomic pressures, which cliallenge the VA system no less than others, it is essential that tests arid techniques be examined rigorously in terms of important benefit to patients. In light o f their prognostic
XVILLIAML. ~,VOLFSON, hiD Hoag Memorial Hospital Presbyterian Newport Beach, California
BOOK REVIEWS in Clinical Cytology, Volume 2, L. Koss and D. Coleman. New York, Masson, 1984. 314 pages, $69.50.
Advances
Tile editors have done a masterful job o f putting together this 12-chapter book covering a variety of recent
developments ill cytology. With 22 contributors, this is not a small feat. T h e book is a collection of articles ranging from practical concepts in cytology to more esoteric subjects that currently have little apparent clinical relevance. This observation is not meant as criticism but rather as a reflec-
650