Acquired immunodeficiency syndrome

CORRESPONDENCE greatly change f o r m factors, which contain tile perimeter magnified to the power o f two. A change in the algorithm was effected by the m a n u f a c t u r e r in sttbsequent versions of the instrument. Measurements with tile instrument in our laboratory (Videoplan Version ,t) showed that inflations o f length m e a s u r e m e n t of 1 to 3 p e r cent, and sometimes u p to 5 to 8 p e r cent, occur with slow light pen speed at 45 ~ orientation to tile x - y axes. Similar inflation o f perimeter was fotmd when tracing regular geometric structures. This e r r o r m a d e it impossible, for example, to arrive at nuclear r o u n d n e s s factors comparable to those published for prostatic carcinomaP A software modification with corrections that allow earlier instrtunents to conform to subsequent versions is available and appears to have eliminated the overestimation o f length/perimeter. T h e applications o f m o r p h o m e t r y a n d interest in this fiekl have been growing rapidly, with diagnostic discrimination a n d reproducibility as an objectiveS.4; however, the hardware and software variations affect the comparisons o f available data. T h e details, snch as the algorithms used to obtain the measurements, and o t h e r factors i n f l u e n c i n g accuracy, are not readily available or u n d e r s t a n d a b l e without expertise in c o m p u t e r p r o g r a m m i n g , n o r do the nmnufacturers/producers communicate the potential o r real errors in p e r f o r m a n c e o f the instruments. T h e r e is a need for standard objective test systems, which would also include observer reproducibility criteria. This a p p e a r s even nmre compelling because o f the variety of instruments available. JAN V. PI'rHA, MD, PttD L a b o r a t o r y Service Veterans Administration Medical Center Oklahoum City, Oklahoma I. Barry JD, Sharkey FE: Observer reproducibility during computer-assisted planimetric measurements of nuclear features. HuM PATIlOL 16:225, 1985 2. CornelisseJTWA, vandenBcrg TJTP: Profile boundary length can be overestimated b)" as much as 41% when using a digitizer tablet. J Microsc 136:341. 1984 3. EpsteinJL, Berry sJ. EgglestonJC: Nuclear roundness factor. Cancer 54:1666, 1984 4. Collan Y: Stereology and morphometD" in pathology: an introduction. Acta Slereol 2:207, 1983 5. BaakJ PA, Oort J: A Manual of Morphometry in DiagnosticPathology. Berlin, lleldelberg, New York, Tok)'o, Springcr-Verlag, 1983

Acquired Immunodeficiency Syndrome To the Editor:--In an interesting article in the April 1985 issue o f HtJ,XtAN PArtlOI_OC;Y, Dr. Sidhu et al. 1 summarize their uhrastructural findings from a stud)" o f AIDS and AIDS-related complex (ARC). T h e article describes in detail the observations that they had published previously in letter and abstract form. 2,3 Many o f their observations have been substantiated by others, and vice versa. 4-9 In addition, several o f the observations are a p p a r e n t l y unique to these researchers, e.g., electron-dense a n m r p h o u s coat over the u r o p o d o f capping lymphocytes, "iron" in mitochondria o f circulating reticulocytes and late normohlasts in b o n e m a r r o w , a n d left shift o f m e g a k a r y o c y t e s a n d platelet phagocytosis. In their Discttssion section, the attthors stress that "for the detection o f these t h r e e markers, it is essential that whole buff)' coat preparations be used" and that "this technique also avoids processing artifacts." T h e y strongly imply that the "straight tubules" that I r e p o r t e d observing 5 in lymphocytes are an artifact d u e to the use o f Ficoll-Hypaque gradient centrifugation to p r e p a r e buff)' coat mononuclear ceils for transmission electron microscopy, possibly

representing damaged basophilic granules. Ahhough straight mbnles are not mentioned in the cited abstract, 5 examples o f these structures were included in the actual p o s t e r p r e s e n t a t i o n . I l o w e v e r , as c l e a r l y s t a t e d in tile poster, I had never observed these structures in buffy coat cells, only in m o n o n u c l e a r cells in lymph nodes and in a thymus removed at autopsy. F u r t h e r m o r e , there was no indication that they were an artifact o f lymph node preparation. A b r i e f discussion o f these findings a p p e a r e d in N o v e m b e r 1984, 7 at least two months after the revised article in question I was accepted for publication. In a subsequent review o f the literature on the nhrastructure o f lymphadenitis I found mention o f structures r e f e r r e d to as "intracytoplasmic rodlets" (ICR), which were present in immunoblasts and a few macrophages of "histiocytic necrotizing lymphadenitis" and "necrotizing lymphadenitis with follicular hyperplasia," sometimes in the same cells c o n t a i n i n g t u b u l o r e t i c u l a r structures (TRS). 10 Straight tubules a n d intracytoplasmic rodlets a p p e a r to be morphologically identical. Eimoto et alA 0 review the brief literature on these structures, which includes rare cases o f dog a n d h u m a n lymphomas and lymphoblastic leukemia. T h e association o f these structures with TRS is also mentioned. T h e s e structures have subsequently been observed in additional lymph nodes o f patients with AIDS and ARC, but as yet never in buff), coat cells. T h e i r composition.and significance remain a mystery. C a p p i n g lymphocytes are also regularly observed in buff)' coats from patients with AIDS and ARC, even when they are p r e p a r e d by Ficoll-Hypaque gradient centrifugation, a h h o u g h the electron-dense a m o r p h o u s coat has been observed only rarely in these preparations. Capping lymphocytes are ahvays in greater a b u n d a n c e in the buff)' coats from patients with AIDS a n d ARC than in control subjects. In addition to the TRS and/or TRF, seen occasionally, tile majority o f capping lymphocytes contain parallel tubular arrays (PI'A), a p r o p o s e d m a r k e r for natural killer ( N K ) lymphocytes. I have also observed that the proportion o f circulating P T A - c o n t a i n i n g lymphocytes in patients with AIDS and ARC is elevated, an interesting observation in light o f the fact that NK cell activity is regularly reported to be d e p r e s s e d in such persons. Finally, I agree that PTAcontaining cells are not seen in lymph nodes, except in the vascular c o m p a r t m e n t . A h h o u g h it is clear that examples o f type C retrovirus can be found in the material that is being reviewed, the "figure a d d e d at p r o o f " is not a convincing example. JAN MARC ORENSTEIN MD, t'tID D e p a r t m e n t o f Pathology George Washington University Medical Center Washington, DC 1. Sidhu GS, Stahl RE, EI-SadrW, et al: The acquired immunodeficiency syndrome: an uhrastructural study, ttUM Pa'rHOL 16:377, 1985 2. Sidhu GS, Stahl RE, EI-SadrW, et al: Uhrastructural markers of AIDS. Lancet 1:990, 1983 3. Sidhu GS, Stahl RE, EI-Sadr W, et al: Uhrastructural features of acquired immune deficiencysyndrome. I~abInvest 50:54A, 1984 4. OrensteinJM: Uhrastructural markers in AIDS. Lancet 2:284, 1983 5. Orenstein JM: Uhrastructural markers in acquired immunodeficiency syndrome patients. Lab Invest 50:44A, 1984 6. Orenstein JM, Schulof RS, Simon GL: Uhrastructural markers in circulating lymphocytes of preacquired immunodeficiency syndrome subjects. Lab Invest 52:.t9A, 1985 7. Orenstein JM, Schulof RS, Simon GL: Uhrastructural markers in AIDS. Arch Pathol Lab Med 108:857. 1984 8. Orenstein JM, Simon GL, KesslerCM, et at: Uhrastructural markers in circulating lymphocytesof subjects at risk for AIDS. In press, Am J Clin Pathol. 1985 9. Grinfley PM. Kang Y-II, Frederick W. et al: Interferon-related leuko-

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cyte inclusions in acquired immune deficiencysyndrome:localization in T cells. AmJ Clin Pathol 81:147, 198.t 10. EimotoT, Kikuchi M, Mitsui T: ltistiocyticnecrotizing lymphadenitis: an ultrastructural study in comparison with other types of lymphadenitis. Acta PatholJpn 33:863, 1983

Concerning Collagen Types in Fibrosarcoma

To the Editor:--Concerning the recent description in HUMAN PATHOLOGY of collagen types in fibrosarcoma by Hall et al., 1 I believe that the diagnosis is not straightforward and can be questioned. First, pure fibrosarcoma is a rare lesion; many similar sarcomas with celhdar areas and a herringbone pattern (not mentioned, but required for fibrosarcoma) may be either malignant schwannomas or monophasic synovial sarcomas in disguise. Thus, this case is not "the most straightforward of these tumors." Second, electron microscopic data, from only one o f the three 11athology specimens, were obtained from the study o f less than ideal formalin-fixed tissue and were discussed only superficially. Third, in my opinion, the age (15 years), site

(lower thigh, knee region), anti natural history all, strongly suggest a diagnosis of monophasic synovial sarcoma. Thus, while I am sure that the authors' conclusions as to the types o f collagen present and their meaning are correct, they may be related to the wrong soft tissue phenotype. I would suggest that, if collagen types are to be correctly associated with various phenotypes, and since such infornmtion wotdd be quite valuable, other supportive studies, such as detailed ultrastt'ucture and, particularly, immunohistochemistry, ought to accompany these analyses. In this way, the phenotype studied would be clearly and accurately defined. JoH• J. BROOKS, MD Department of Pathology & l.aboratory Medicine I Iospital o f the University of I'ennsylvania Philadelphia, Pennsylvania I. llallJ, Tsang S, Timpl R, et ah Collagentypes in fibrosarcoma:absence of type 3 collagen in reticulin, tlust PAItIOL16:-t39, 1985

BOOK REVIEWS Textbook of Neuropathology, edited by R. L. Davis anti D. M. Robertson. Baltimore, Williams and Wilkins, 1984. 900 pages, $110.00. "Finally, you have a choice in neuropathology texts"; so reads the promotional brochure for the new Textbook of Neuropathology edited by Richard L. Davis and David M. Robertson, with 17 chapters from 21 contributors. T h e volume represents it comprehensive, up-to-date treatise on nearly all major subjects in neuropathology, designed to be "useful to general pathologists, neurosurgeons, and neurologists as well as neuropathologists." It is well organized and readably written in sufficient d e p t h and detail to present its subjects clearly but to avoid tedious pedantry. It also provides a superb list o f references on each subject, including a n u m b e r of historical interest and many current, as late as early 1984, all well annotated throughottt each chapter. Consistently high quality o f photographic reproduction does seem to be lacking overall; contrast is often too harsh, or, in some instances, backgrounds are too gray. A number o f concise tables and diagrams are informative and add significant information. The reader or potential reader should be aware that, for reasons stated by the editors in the preface, three areas of neuropathology were intentionally omitted, specifically nervous system neoplasms, peripheral nerve pathology, attd disease of muscle. That notwithstanding, the book provides useful and understandable information on subjects in neuropathology that have very often been considered confitsing or vague. The choice provided by this new text is valid, at:el it should be a welcome addition to the resource literatttre for students, postgraduate trainees, and practicing professionals interested in a number o f current concepts in neuropathology.~Wn.t.bxM O. ~VttI'7.TSEt.L,JR, MI), Department

of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee. Clinical Epidemiology, Ah'an R. Feinstein, MD. Philadelphia, WB S:mnders, 198~. 812 pages, $60.00. Epidemiologic and statistical information affects us all; new reports and conclusions appear in the news media daily. How are pathologists, o t h e r physicians, and the public t o j n d g e the qnality, accuracy, and objectivity of the

massive flow of statistical epidemiologic research? I f one is neither trained in statistical theory or practice nor gifted mathematically, one is likely at the mercy of those who are. Feinstein's new Clinical ls is a clear, witty, comprehensive, and eminently iiPstructive tutorial course in how to do medical epidemiologic studies and how to evaluate the publications. The chapters end with exercises, as in an old-fashioned arithmetic book, and the answers in the back are both educational and refreshing: "Ans 1 2 . 4 . . . T h e dccision here is largely a nmtter of ideologic viewpoint with respect to the role of individuals, industry, and government in a free society. As long as reasonable evidence can be offered, Bayer has the right to advertise that it is " b e t t e r " , . . . Members of the public have the right and the responsibility to be skeptical about advertising claims..." Once the reader knows more about the strengths and weaknesses o f case-control, cross-sectional, cohort, and noncohort research studies and appreciates the difference between mathematical significance and biologic significance probabilities, a m o n g other important distinctions, the medical literature can be read more critically and profitably. Susceptibility bias, d i a g n o s t i c a s c e r t a i n m e n t bias, the missing denominator, epidemiologic artifacts, and many other sources o f confusion and e r r o r are explained so clearly that even this reviewer was able to understand. It is a book worth reading and rereading in the present age of uncertainty.--SHELDO• C. SO.XtMERS, MD, Council for To-

bacco Research, New York, New York. Biomedical Bestiary: An Epidemiologic Guide to Flaws and Fallacies in the Medical Literature, Max Michael IIl, MD, W. Thomas Boyce, MD, and Allen J. Wilcox, MD, PhD. Boston, Little, Brown, 1984. 161 pages, $12.50. If you appreciate Feinstein's Clinical Epidendology, you will enjoy tile cartoons and brief text o f this small paperback. "It describes the strange and wily beasts that htrk, sallow and yellow-eyed, in tile most respectable medical studies." Characters include the Grand Confounder, Diagnostic Accuracy Bias (the con man o f the biomedical bestiary), and the beady-eyed Significance Turkey, a m o n g others. T h e tone is warm, charnfing, and sensitive to the need for good medical science.--SllELDON C. SOMMERS, MD, Council for Tobacco Research, New York, New York.