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bcl-2 immunoexpression in MALT-lymphomas
HUMAN PATHOLOGY
Volume 27, No. 11 (November 1996)
The above letter was referred to the authors of the article in question, who offer the foUowing reply: To the Editor:--In response to the letter of Dr Jeffers regarding our article on cadherins expression in pleural mesotheliomas and lung adenocarcinomas, 1 we would like to emphasize some important aspects of our findings and make some recommendations for the use of cadherins in the differential diagnosis of these tumors. In our study, N-cadherin was strongly expressed in all mesotheliomas, regardless of the histological type, and located with particular intensity in the areas of cell-cell contact, confirming previous observations in mesothelioma cell lines. 2 As we acknowledged in our article (p 1366), some mesotheliomas showed detectable E-cadherin, although the expression was focal, weak, and mostly cytoplasmic. Conversely, E-cadherin was strongly expressed in lung adenocarcinomas, although focal cytoplasmic N-cadherin was detectable in few tumor cells in a minority of cases. We have e x t e n d e d our study to formalin-fixed and p a r a f f i n - e m b e d d e d tumors, i n c l u d i n g paraffin blocks of pleural effusions. Using antigen retrieval methods, we have confirmed our original findings in frozen sections (Han AC, Peralta Soler A, Knudsen KA et al: m a n u s c r i p t submitted.) DrJeffers, using a commercially available E-cadherin antibody, indicates strong expression of E-cadherin in cytospin preparations of pleural effusion cells (two cases, only one confirmed as mesothelioma by biopsy). In our opinion, Dr Jeffers is using the wrong approach for the immunocytochemical diagnosis of pleural effusions. In our experience, the damage of cell membranes and cytoplasmic structures induced by cytospin preparations of pleural effusions has the potential for generating nonspecific or unreliable immunoreactions. This is particularly important when the antigen to study is a cell membrane protein. An example of such technical problems is demonstrated in the micrograph provided by Dr Jeffers, showing diffuse cytoplasmic but not plasma membrane staining. In light of the interest p r o m p t e d by our article, we would like to make the following recommendations in the use of cadherins as markers for the differential diagnosis of lung adenocarcinomas and mesotheliomas: 1. The specificity of each of the anti-cadherin antib0dies should be tested by Western immunoblots in cells expressing only E- or N-cadherin, prior to their use in immunohistochemistry. We have found unacceptable background in some of the commercially available anti-cadherin antibodies (Knudsen, Peralta Soler, unpublished observations, 1996). 2. To evaluate the intensity and specificity of the immunohistochemical reactions, both anti-N-cadherin and anti-E-cadherin antibodies should be used as a panel in the differential diagnosis of these tumors. High Ncadherin expression combined with absent or low Ecadherin is characteristic of pleural mesotheliomas, whereas lung adenocarcinomas express high levels of E-cadherin with little or no N-cadherin. 3. Pleural effusions should be processed as cell blocks rather than cytospin preparations when using cadherin antibodies for diagnostic immunocytochemistry. With these considerations, we believe that the differential expression of N-cadherin and E-cadherin is a valuable tool to distinguish pleural mesothelioma from lung adenocarcinoma.
We thank Dr Jeffers for his interest in our study. ALEJANDRO PERALTASOLER, MD, PHD KAREN A. KNUDSEN, PHD The Lankenau Medical Research Center Wynnewood, PA HERNANDO SALAZAR,MD, MPH Department of Pathology The Reading Hospital and Medical Center Reading, PA 1. PeraRaSolerA, KnudsenKA,Jaurand M-C,et al: The differentialexpression of N-cadherinand E-cadherindistinguishespleural mesotheliomasfrom lung adenocarcinomas.HUMPATHOL26:1363-1369, 1995 2. Pelin K, HirvonenA, LinnainmaaK: Expressionof cell adhesionmolecules and connexins in gap junctional intercellular communicationdeficient human mesotheliomatumour cell lines and communication competent primary mesothelialcells.Carcinogenesis15:2673-2675, 1994
bcl-2 Immunoexpression in MALTLymphomas To the Editor:--We would like to comment on a recent article by Nakamura and colleagues that appeared in HUMAN PATHOLOGY.I We also analyzed the relationship between bcl-2 and p53 proteins in MALT-lymphomas occurring in the thyroid gland. 2 The findings of our study and the larger one of Nakamura et al are consonant: low-grade MALT-lymphomas have large amounts of immunodetectable bcl-2 with little p53 staining; while high-grade lymphomas are bcl-2 negative and strongly p53 positive. Both studies indicate that an inverse relationship exists between bcl-2 and p53 protein expression in the setting of MALT-lymphomas. An interesting facet to our study was the bcl-2 staining pattern seen in two low-grade MALT-lymphomas with a follicular pattern, z The neoplastic follicles consisted of centr0cytes and centroblasts and were largely negative for bcl2. Both the lymphomas conformed histologically with MALTlymphomas in other respects. This lack of bcl-2 staining in the neoplastic follicles in the MALT-lymphomas is in stark contrast with that seen in follicular lymphomas within lymph nodes, which are usually strongly bcl-2 positive. To further elucidate this problem, low-grade lymphomas with a follicular pattern were investigated in other MALT sites: parotid, lung, and gastrointestinal tract, as well as in the skin. Histologically, all the follicular structures were obviously neoplastic: composed of centrocytes and centroblasts, lacking tingible body macrophages and a mantle zone. Other areas of the lymphomas were typical of MALT-omas: lympho-epithelial lesions formed by centrocyte-like cells and parafollicular aggregates of plasma cells. Staining for bcl-2 protein, again, was negafive. A proliferation marker, Ki-67, did not indicate a high proliferation rate. It has been shown previously that "colonized" follicles in MALT-lymphomas are bcl-2 negative.3 However, the centrocyte-like cells have been shown to be bcl-2 positive in lympho-epithelial lesions. Thus, colonization of reactive follicles would not appear to be the most likely cause for the bcl-2 negativity. It, therefore, seems that there is a subset of low-grade MALTlymphomas that have a follicular pattern, and these follicles are negative for bcl-2 protein. The exact cause for this staining reaction remains somewhat enigmatic.
RUNJAN CI-IETTY,FRCPA Department of Anatomical Pathology University of Natal Medical School Durban, South Africa KEVIN C. GATTER, MRCPath University Department of Cellular Science University of Oxford Oxford, UK
BOOK REVIEWS 1. Nakamura S, AkazawaK, Kinukawa N, et al: Inverse correlation between expression ofbcl-2 and p53 proteins in primary gastric lymphoma. HUMPATHOL 27:225-233, 1996 2. Cherty R, O'Leary.lJ, Biddolph SC, et al: hnmunohistochemical detection of p53 and Bcl-2 proteins in Hashimoto's thyroiditis and primary thyroid lymphomas. J Clin Pathol 48:239-241, 1995 3. Isaacson PG, Wotherspoon AC, Diss TC, et al: bcl-2 expression in lymphomas. Lancet 337:175-176, 1991
The above letter was referred to the authors of the article in question who offer the foUowing reply: To the Editor:--We t h a n k Drs. C h e t t y a n d G a t t e r for t h e i r c o m m e n t s r e g a r d i n g o u r article. 1 Based o n t h e i r suggestions, we r e e v a l u a t e d t h e bcl-2 i m m u n o e x p r e s s i o n p a t t e r n a n d Ki67 (MIB-1) l a b e l i n g i n d e x 2 in 25 cases of gastric low-grade MALT l y m p h o m a with a n e v i d e n t follicular colonization, 3 a n d c o m p a r e d t h e m with t h o s e in 7 cases o f gastric follicular (centroblastic-centrocytic) l y m p h o m a . As a result, most neoplastic cells within the colonized follicles in all e x a m i n e d MALT l y m p h o m a s were bcl-2 negative, in contrast to the diffusely bcl-2 positive centrocyte-like cells outside the follicles, as well as those in the lymphoepithelial lesions. Conversely, five of seven e x a m i n e d follicular lymphomas showed a n intense bcl-2 expression in the neoplastic follicular cells. T h e MIB-1 (Ki-67) labeling indexes o f the neoplastic cells within the colonized follicles of MALT lynaphomas (mean, 56.3%), which were markedly h i g h e r t h a n those outside the follicles (mean, 15.6%), were also significantly h i g h e r t h a n those of follicular lymphomas (mean, 27.1%) (Mann-Whitney U test, P < .001). These results were compatible with those in the previously published description of lsaacson et al. ~ " L o w g r a d e l y m p h o m a s with a follicular p a t t e r n " of C h e t t y et al5 s e e m to b e identical with low-grade MALT l y m p h o m a s with a follicualr colonization, 3 a c c o r d i n g to t h e i r d e s c r i b e d m o r p h o l o g y a n d bcl-2 i m m u n o s t a i n i n g patterns. 5 B o t h t h e results of Isaacson et al4 a n d ours c o n c e r n i n g bcl-2 a n d Ki-67 i m m u n o s t a i n i n g thus suggest a close association b e t w e e n t h e p r o l i f e r a t i n g activity a n d t h e failure to express bcl-2 p r o t e i n . We, t h e r e f o r e , speculate t h a t such follicular c o l o n i z a t i o n m a y b e e i t h e r a p r e c u r s o r o r a n initial state o f h i g h - g r a d e t r a n s f o r m a t i o n i n MALT l y m p h o m a s . SHOTARO N ~ ' a U R A , MD MASAZUMI TSUNEYOSHI, MD Second Department of Pathology Faculty o f M e d i c i n e Kyushu University Fukuoka, J a p a n
1. Nakamura S, AkazawaK, KinukawaN, et al: Inverse correlation between the expression of bcl-2 and p53 proteins in primary gastric lymphoma. HUM PATNOL27:225-233, 1996 2. Nakamura S, Akazawa K, Yao T, et al: Primary gastric lymphoma: A clinicopathologic study of 233 cases with special reference to evaluation with the MIB-1 index. Cancer 76:1313-1324, 1995 3. Isaacson PG, Wotherspoon AC, Diss T, et al: Follicular colonization in B-celI lymphoma of mucosa-associated lymphoid tissue. Am J Surg Pathol 15:819-828, 1991 4. Isaacson PG, Wotherspoon AC, Diss TC, et al: bcl-2 expression in lymphomas. Lancet 337:175-176, 1991 5. Chetty R, O'Leary~, Biddolph SC, et al: Immunohistochemical detection of p53 and Bcl-2 proteins in Hashimoto's thyroiditis and primary thyroid lymphomas. J Clin Pathol 48:239-241, 1995
D u c t a l C a r c i n o m a In Situ To the Editor:--The letter to t h e e d i t o r by N a r e s h a n d Borges, ~ in w h i c h they raise t h e possibility of ductal c a r c i n o m a in situ with p e r i d u c t a l fibrosis b e i n g in reality a n invasive c a r c i n o m a , r e m i n d e d m e o f t h e m u s i n g s o f a n o t h e r Borges (Jorge Luis) a b o u t the circular n a t u r e of time a n d h o w this results in events a n d ideas r e c u r r i n g with m a t h e m a t i c a l regularity. 2 T h e thesis raised by t h e a u t h o r s a n d t h e p o i n t s pres e n t e d in its s u p p o r t are practically identical to those esp o u s e d by a n Italian pathologist, Carlo Sirtori, in 1967, at t h e time h e was h e a d o f the p a t h o l o g y d e p a r t m e n t o f t h e C a n c e r Institute i n Milan, Italy. s Even t h e t e r m i n o l o g y used is eerily similar. To wit, N a r e s h a n d Borges q u o t e a p r e s e n t a t i o n m a d e in New D e l h i in 1994, e n t i t l e d " D C I S is n o t a c a r c i n o m a in situ. ''4 Sirtori et al s h a d e n t i t l e d t h e i r 1967 paper, " I n t r a d u c tal c a r c i n o m a of t h e b r e a s t is n e v e r a c a r c i n o m a in situV' W e r e it n o t for t h e e m p h a t i c never (an a d v e r b t h a t cautious writers r e c o m m e n d n e v e r b e used), o n e m i g h t have t h o u g h t t h a t Sirtori's p a p e r r e i n c a r n a t e d itself in I n d i a a l m o s t 30 years after h a v i n g b e e n conceived. JUaN ROSA~, MD Chairman, Department of Pathology M e m o r i a l Sloane K e t t e r i n g C a n c e r C e n t e r New York, NY 1. Naresh KN, Borges AM: Ductal carcinoma in situ with periductal fibrosis-Is it in reality an invasive carcinoma? HUM PATHOL27:744, 1996 (Correspondence) 2. Borges JL: "La doctrina de los ciclos" and "El tiempo circular," in Historia de la eternidad. Buenos Aires, Emec6, 1953 3. Sirtori C, Talamazzi F: II carcinoma della mammella non 6 mai un carcinoma in situ. Tumori 53:641-644, 1967 4. Querei Della-Fevere G, Levene A: DCIS is not a carcinoma in situ. A hypothesis. XVI International Cancer Congress, 1994, New Delhi, India, Abstract book I, OPBR2-10
BOOK REVIEWS The Pathology of Congenital Heart Disease. A Personal Experience with more than 6,300 Congenitally Malformed Hearts, Vols 1 a n d 2. Saroja B h a r a t i a n d M a u r i c e Lev. A r m o n k , NY, F u t u r a P u b l i s h i n g C o m p a n y , Inc, 1996, 1,554 pages, $395.00. This w e l l - p r o d u c e d b o o k is profusely illustrated with black a n d white p i c t u r e s (the majority of w h i c h are o f a h i g h s t a n d a r d ) a n d sparse diagrams. T h e b o o k is a c o m p e n d i u m o f the c o m b i n e d e x p e r i e n c e in t h e p a t h o l o g y o f c o n g e n i t a l h e a r t disease o f D r B h a r a t i a n d t h e late D r Lev. Early c h a p t e r s deal with t h e m e t h o d s o f e x a m i n a t i o n a n d dissection o f t h e heart, cardiac embryology, as well as t e r m i n o l o g y a n d classification. T h e classification u s e d by t h e a u t h o r s is b a s e d o n t h e
c o n c e p t o f a c o m p l e x a n d this has led to a c h a p t e r o r d e r a n d g r o u p i n g o f c o n g e n i t a l cardiac a b n o r m a l i t i e s , w h i c h some readers m a y find idiosyncratic. O n page 15, in discussing t h e course o f t h e i n f e r i o r v e n a cava, t h e r e a d e r is puzzled to r e a d t h a t " T h e h e p a t i c vein may e n t e r t h e r i g h t or t h e left a t r i u m . " R e f e r e n c e s to t h e literature are given at t h e e n d of only 5 of the 98 chapters, b u t a f u r t h e r 269 u n c a t e g o r i z e d r e f e r e n c e s are given at t h e e n d of v o l u m e 2. The chapter on "Postoperative Congenital Hearts" would have b e n e f i t e d the less-expert r e a d e r if a b r i e f description o f e a c h o f t h e operative p r o c e d u r e s (eg, t h e F o n t a n a n d N o r w o o d p r o c e d u r e s ) discussed h a d b e e n given. At first glance, t h e b o o k a p p e a r s to b e o n e t h a t all pathologists a n d clinicians with a n i n t e r e s t in c o n g e n i t a l h e a r t dis-
1247
Volume 27, No. 11 (November 1996)
The above letter was referred to the authors of the article in question, who offer the foUowing reply: To the Editor:--In response to the letter of Dr Jeffers regarding our article on cadherins expression in pleural mesotheliomas and lung adenocarcinomas, 1 we would like to emphasize some important aspects of our findings and make some recommendations for the use of cadherins in the differential diagnosis of these tumors. In our study, N-cadherin was strongly expressed in all mesotheliomas, regardless of the histological type, and located with particular intensity in the areas of cell-cell contact, confirming previous observations in mesothelioma cell lines. 2 As we acknowledged in our article (p 1366), some mesotheliomas showed detectable E-cadherin, although the expression was focal, weak, and mostly cytoplasmic. Conversely, E-cadherin was strongly expressed in lung adenocarcinomas, although focal cytoplasmic N-cadherin was detectable in few tumor cells in a minority of cases. We have e x t e n d e d our study to formalin-fixed and p a r a f f i n - e m b e d d e d tumors, i n c l u d i n g paraffin blocks of pleural effusions. Using antigen retrieval methods, we have confirmed our original findings in frozen sections (Han AC, Peralta Soler A, Knudsen KA et al: m a n u s c r i p t submitted.) DrJeffers, using a commercially available E-cadherin antibody, indicates strong expression of E-cadherin in cytospin preparations of pleural effusion cells (two cases, only one confirmed as mesothelioma by biopsy). In our opinion, Dr Jeffers is using the wrong approach for the immunocytochemical diagnosis of pleural effusions. In our experience, the damage of cell membranes and cytoplasmic structures induced by cytospin preparations of pleural effusions has the potential for generating nonspecific or unreliable immunoreactions. This is particularly important when the antigen to study is a cell membrane protein. An example of such technical problems is demonstrated in the micrograph provided by Dr Jeffers, showing diffuse cytoplasmic but not plasma membrane staining. In light of the interest p r o m p t e d by our article, we would like to make the following recommendations in the use of cadherins as markers for the differential diagnosis of lung adenocarcinomas and mesotheliomas: 1. The specificity of each of the anti-cadherin antib0dies should be tested by Western immunoblots in cells expressing only E- or N-cadherin, prior to their use in immunohistochemistry. We have found unacceptable background in some of the commercially available anti-cadherin antibodies (Knudsen, Peralta Soler, unpublished observations, 1996). 2. To evaluate the intensity and specificity of the immunohistochemical reactions, both anti-N-cadherin and anti-E-cadherin antibodies should be used as a panel in the differential diagnosis of these tumors. High Ncadherin expression combined with absent or low Ecadherin is characteristic of pleural mesotheliomas, whereas lung adenocarcinomas express high levels of E-cadherin with little or no N-cadherin. 3. Pleural effusions should be processed as cell blocks rather than cytospin preparations when using cadherin antibodies for diagnostic immunocytochemistry. With these considerations, we believe that the differential expression of N-cadherin and E-cadherin is a valuable tool to distinguish pleural mesothelioma from lung adenocarcinoma.
We thank Dr Jeffers for his interest in our study. ALEJANDRO PERALTASOLER, MD, PHD KAREN A. KNUDSEN, PHD The Lankenau Medical Research Center Wynnewood, PA HERNANDO SALAZAR,MD, MPH Department of Pathology The Reading Hospital and Medical Center Reading, PA 1. PeraRaSolerA, KnudsenKA,Jaurand M-C,et al: The differentialexpression of N-cadherinand E-cadherindistinguishespleural mesotheliomasfrom lung adenocarcinomas.HUMPATHOL26:1363-1369, 1995 2. Pelin K, HirvonenA, LinnainmaaK: Expressionof cell adhesionmolecules and connexins in gap junctional intercellular communicationdeficient human mesotheliomatumour cell lines and communication competent primary mesothelialcells.Carcinogenesis15:2673-2675, 1994
bcl-2 Immunoexpression in MALTLymphomas To the Editor:--We would like to comment on a recent article by Nakamura and colleagues that appeared in HUMAN PATHOLOGY.I We also analyzed the relationship between bcl-2 and p53 proteins in MALT-lymphomas occurring in the thyroid gland. 2 The findings of our study and the larger one of Nakamura et al are consonant: low-grade MALT-lymphomas have large amounts of immunodetectable bcl-2 with little p53 staining; while high-grade lymphomas are bcl-2 negative and strongly p53 positive. Both studies indicate that an inverse relationship exists between bcl-2 and p53 protein expression in the setting of MALT-lymphomas. An interesting facet to our study was the bcl-2 staining pattern seen in two low-grade MALT-lymphomas with a follicular pattern, z The neoplastic follicles consisted of centr0cytes and centroblasts and were largely negative for bcl2. Both the lymphomas conformed histologically with MALTlymphomas in other respects. This lack of bcl-2 staining in the neoplastic follicles in the MALT-lymphomas is in stark contrast with that seen in follicular lymphomas within lymph nodes, which are usually strongly bcl-2 positive. To further elucidate this problem, low-grade lymphomas with a follicular pattern were investigated in other MALT sites: parotid, lung, and gastrointestinal tract, as well as in the skin. Histologically, all the follicular structures were obviously neoplastic: composed of centrocytes and centroblasts, lacking tingible body macrophages and a mantle zone. Other areas of the lymphomas were typical of MALT-omas: lympho-epithelial lesions formed by centrocyte-like cells and parafollicular aggregates of plasma cells. Staining for bcl-2 protein, again, was negafive. A proliferation marker, Ki-67, did not indicate a high proliferation rate. It has been shown previously that "colonized" follicles in MALT-lymphomas are bcl-2 negative.3 However, the centrocyte-like cells have been shown to be bcl-2 positive in lympho-epithelial lesions. Thus, colonization of reactive follicles would not appear to be the most likely cause for the bcl-2 negativity. It, therefore, seems that there is a subset of low-grade MALTlymphomas that have a follicular pattern, and these follicles are negative for bcl-2 protein. The exact cause for this staining reaction remains somewhat enigmatic.
RUNJAN CI-IETTY,FRCPA Department of Anatomical Pathology University of Natal Medical School Durban, South Africa KEVIN C. GATTER, MRCPath University Department of Cellular Science University of Oxford Oxford, UK
BOOK REVIEWS 1. Nakamura S, AkazawaK, Kinukawa N, et al: Inverse correlation between expression ofbcl-2 and p53 proteins in primary gastric lymphoma. HUMPATHOL 27:225-233, 1996 2. Cherty R, O'Leary.lJ, Biddolph SC, et al: hnmunohistochemical detection of p53 and Bcl-2 proteins in Hashimoto's thyroiditis and primary thyroid lymphomas. J Clin Pathol 48:239-241, 1995 3. Isaacson PG, Wotherspoon AC, Diss TC, et al: bcl-2 expression in lymphomas. Lancet 337:175-176, 1991
The above letter was referred to the authors of the article in question who offer the foUowing reply: To the Editor:--We t h a n k Drs. C h e t t y a n d G a t t e r for t h e i r c o m m e n t s r e g a r d i n g o u r article. 1 Based o n t h e i r suggestions, we r e e v a l u a t e d t h e bcl-2 i m m u n o e x p r e s s i o n p a t t e r n a n d Ki67 (MIB-1) l a b e l i n g i n d e x 2 in 25 cases of gastric low-grade MALT l y m p h o m a with a n e v i d e n t follicular colonization, 3 a n d c o m p a r e d t h e m with t h o s e in 7 cases o f gastric follicular (centroblastic-centrocytic) l y m p h o m a . As a result, most neoplastic cells within the colonized follicles in all e x a m i n e d MALT l y m p h o m a s were bcl-2 negative, in contrast to the diffusely bcl-2 positive centrocyte-like cells outside the follicles, as well as those in the lymphoepithelial lesions. Conversely, five of seven e x a m i n e d follicular lymphomas showed a n intense bcl-2 expression in the neoplastic follicular cells. T h e MIB-1 (Ki-67) labeling indexes o f the neoplastic cells within the colonized follicles of MALT lynaphomas (mean, 56.3%), which were markedly h i g h e r t h a n those outside the follicles (mean, 15.6%), were also significantly h i g h e r t h a n those of follicular lymphomas (mean, 27.1%) (Mann-Whitney U test, P < .001). These results were compatible with those in the previously published description of lsaacson et al. ~ " L o w g r a d e l y m p h o m a s with a follicular p a t t e r n " of C h e t t y et al5 s e e m to b e identical with low-grade MALT l y m p h o m a s with a follicualr colonization, 3 a c c o r d i n g to t h e i r d e s c r i b e d m o r p h o l o g y a n d bcl-2 i m m u n o s t a i n i n g patterns. 5 B o t h t h e results of Isaacson et al4 a n d ours c o n c e r n i n g bcl-2 a n d Ki-67 i m m u n o s t a i n i n g thus suggest a close association b e t w e e n t h e p r o l i f e r a t i n g activity a n d t h e failure to express bcl-2 p r o t e i n . We, t h e r e f o r e , speculate t h a t such follicular c o l o n i z a t i o n m a y b e e i t h e r a p r e c u r s o r o r a n initial state o f h i g h - g r a d e t r a n s f o r m a t i o n i n MALT l y m p h o m a s . SHOTARO N ~ ' a U R A , MD MASAZUMI TSUNEYOSHI, MD Second Department of Pathology Faculty o f M e d i c i n e Kyushu University Fukuoka, J a p a n
1. Nakamura S, AkazawaK, KinukawaN, et al: Inverse correlation between the expression of bcl-2 and p53 proteins in primary gastric lymphoma. HUM PATNOL27:225-233, 1996 2. Nakamura S, Akazawa K, Yao T, et al: Primary gastric lymphoma: A clinicopathologic study of 233 cases with special reference to evaluation with the MIB-1 index. Cancer 76:1313-1324, 1995 3. Isaacson PG, Wotherspoon AC, Diss T, et al: Follicular colonization in B-celI lymphoma of mucosa-associated lymphoid tissue. Am J Surg Pathol 15:819-828, 1991 4. Isaacson PG, Wotherspoon AC, Diss TC, et al: bcl-2 expression in lymphomas. Lancet 337:175-176, 1991 5. Chetty R, O'Leary~, Biddolph SC, et al: Immunohistochemical detection of p53 and Bcl-2 proteins in Hashimoto's thyroiditis and primary thyroid lymphomas. J Clin Pathol 48:239-241, 1995
D u c t a l C a r c i n o m a In Situ To the Editor:--The letter to t h e e d i t o r by N a r e s h a n d Borges, ~ in w h i c h they raise t h e possibility of ductal c a r c i n o m a in situ with p e r i d u c t a l fibrosis b e i n g in reality a n invasive c a r c i n o m a , r e m i n d e d m e o f t h e m u s i n g s o f a n o t h e r Borges (Jorge Luis) a b o u t the circular n a t u r e of time a n d h o w this results in events a n d ideas r e c u r r i n g with m a t h e m a t i c a l regularity. 2 T h e thesis raised by t h e a u t h o r s a n d t h e p o i n t s pres e n t e d in its s u p p o r t are practically identical to those esp o u s e d by a n Italian pathologist, Carlo Sirtori, in 1967, at t h e time h e was h e a d o f the p a t h o l o g y d e p a r t m e n t o f t h e C a n c e r Institute i n Milan, Italy. s Even t h e t e r m i n o l o g y used is eerily similar. To wit, N a r e s h a n d Borges q u o t e a p r e s e n t a t i o n m a d e in New D e l h i in 1994, e n t i t l e d " D C I S is n o t a c a r c i n o m a in situ. ''4 Sirtori et al s h a d e n t i t l e d t h e i r 1967 paper, " I n t r a d u c tal c a r c i n o m a of t h e b r e a s t is n e v e r a c a r c i n o m a in situV' W e r e it n o t for t h e e m p h a t i c never (an a d v e r b t h a t cautious writers r e c o m m e n d n e v e r b e used), o n e m i g h t have t h o u g h t t h a t Sirtori's p a p e r r e i n c a r n a t e d itself in I n d i a a l m o s t 30 years after h a v i n g b e e n conceived. JUaN ROSA~, MD Chairman, Department of Pathology M e m o r i a l Sloane K e t t e r i n g C a n c e r C e n t e r New York, NY 1. Naresh KN, Borges AM: Ductal carcinoma in situ with periductal fibrosis-Is it in reality an invasive carcinoma? HUM PATHOL27:744, 1996 (Correspondence) 2. Borges JL: "La doctrina de los ciclos" and "El tiempo circular," in Historia de la eternidad. Buenos Aires, Emec6, 1953 3. Sirtori C, Talamazzi F: II carcinoma della mammella non 6 mai un carcinoma in situ. Tumori 53:641-644, 1967 4. Querei Della-Fevere G, Levene A: DCIS is not a carcinoma in situ. A hypothesis. XVI International Cancer Congress, 1994, New Delhi, India, Abstract book I, OPBR2-10
BOOK REVIEWS The Pathology of Congenital Heart Disease. A Personal Experience with more than 6,300 Congenitally Malformed Hearts, Vols 1 a n d 2. Saroja B h a r a t i a n d M a u r i c e Lev. A r m o n k , NY, F u t u r a P u b l i s h i n g C o m p a n y , Inc, 1996, 1,554 pages, $395.00. This w e l l - p r o d u c e d b o o k is profusely illustrated with black a n d white p i c t u r e s (the majority of w h i c h are o f a h i g h s t a n d a r d ) a n d sparse diagrams. T h e b o o k is a c o m p e n d i u m o f the c o m b i n e d e x p e r i e n c e in t h e p a t h o l o g y o f c o n g e n i t a l h e a r t disease o f D r B h a r a t i a n d t h e late D r Lev. Early c h a p t e r s deal with t h e m e t h o d s o f e x a m i n a t i o n a n d dissection o f t h e heart, cardiac embryology, as well as t e r m i n o l o g y a n d classification. T h e classification u s e d by t h e a u t h o r s is b a s e d o n t h e
c o n c e p t o f a c o m p l e x a n d this has led to a c h a p t e r o r d e r a n d g r o u p i n g o f c o n g e n i t a l cardiac a b n o r m a l i t i e s , w h i c h some readers m a y find idiosyncratic. O n page 15, in discussing t h e course o f t h e i n f e r i o r v e n a cava, t h e r e a d e r is puzzled to r e a d t h a t " T h e h e p a t i c vein may e n t e r t h e r i g h t or t h e left a t r i u m . " R e f e r e n c e s to t h e literature are given at t h e e n d of only 5 of the 98 chapters, b u t a f u r t h e r 269 u n c a t e g o r i z e d r e f e r e n c e s are given at t h e e n d of v o l u m e 2. The chapter on "Postoperative Congenital Hearts" would have b e n e f i t e d the less-expert r e a d e r if a b r i e f description o f e a c h o f t h e operative p r o c e d u r e s (eg, t h e F o n t a n a n d N o r w o o d p r o c e d u r e s ) discussed h a d b e e n given. At first glance, t h e b o o k a p p e a r s to b e o n e t h a t all pathologists a n d clinicians with a n i n t e r e s t in c o n g e n i t a l h e a r t dis-
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