Histopathology 1978. 2, 47-52
Yellow-brown spindle bodies in mesenteric lymph nodes: a possible relationship with melanosis coli M.HALL* & V.EUSEBI Department of Histopathology, Royal Postgraduate Medical School, Hammersmith Hospital, Ducane Road, London Wr2 oHS Accepted for publication 23 September 1977 HALLM. & EUSEBIV. (1978)Histopathology
2, 47-52
Yellow-brown spindle bodies in mesenteric lymph nodes: a possible relationship with melanosis coli Four cases are described in which spindle-shaped, yellow-brown bodies were seen in the mesenteric lymph nodes of patients with melanosis coli. A comparison of the staining reactions and ultrastructural appearances of the spindle bodies and melanosis pigment suggest that they are related within the broad group of lipofuscins and that the spindle bodies are formed as a result of coalescence of lysosomes containing the pigment. Keywords: spindle bodies, lipofuscin, lymph node inclusions, melanosis coli
Introduction The occurrence of spindle-shaped, yellow-brown bodies in human lymph nodes has been known since Hamazaki’s description in 1938 (Hamazaki 1938). At one time these were thought to occur only in patients with sarcoidosis (Carter, Gross & Johnson 1969) but they are now known to occur in a variety of diseases (Boyd & Valentine 1970). Recent investigations of these bodies have shown them to consist of lipofuscin (Sieracki & Fisher 1973) and to have the ultrastructural appearance of giant lysosomes (Doyle, Brahman & Burgess 1973). We have encountered these bodies in the regional lymph nodes removed during colonic surgery in four patients in whom the colon showed coincidental melanosis coli. The similarities and possible relationship between the pigments are discussed.
Materials and methods The material examined was surgically removed formalin fixed colon and regional
* Address for correspondence and reprints: M.Hall, Department of Histopathology, St. George’s Hospital Medical School, Cranmer Terrace, Tooting, London SW17 ORE. 0309-0167/78/0100-0047$02.00 01978Blackwell Scientific Publications.
47
48
M.Hall and V.Eusebi
lymph nodes from a resected adenomatous polyp (Case I), two cases of adenocarcinoma (Cases z & 3) and one case of colonic ulceration and stricture following pelvic radiotherapy (Case 4). The presence of melanosis coli and spindle bodies in the regional lymph nodes was noted in Case I and subsequent colonic resections with melanosis pigment were examined for the presence of spindle bodies in the regional lymph nodes. Sections of paraffin wax-embedded material of each specimen were examined by the methods listed in Table I.Staining was performed by routine methods (Pearse 1972)and unstained paraffin sections were also examined in polarized light and for the presence of autofluorescence with a Leitz ultra violet microscope using BG 38 plus BG 12excitation filters and a K530 barrier filter. Portions of formalin-fixed material from Case I were post-fixed in osmium tetroxide, embedded in epon, ultrathin sections cut, stained with lead citrate and uranyl acetate and examined by electron microscopy.
Results All four cases showed melanosis coli with macrophages containing brown pigment granules present in the lamina propria of the colon. Similar pigment was present
Figure I. Case 2. Lymph node showing spindle bodies in some of which a central poorly-stained zone is seen. Schmorl x 400.
Melanosis and spindle bodies
49
Figure 2. Case I . Colon showing melanosis pigment in macrophages in lamina propria and spindle bodies (arrowed) in sub-mucosal lymphoid tissue. PAS x 400.
within macrophages in the regional lymph nodes and the staining characteristics of this pigment were identical to that in the lamina propria. Spindle bodies were present in lymph nodes in all four cases, the number present varied from scanty in Case 3 to Table r. Comparison of staining reactions of the melanosis pigment and spindle bodies
Staining method PAS PAS after diastase Schmorl Long ZN Masson-Fontana Sudan black on paraffin sections Alcian blue pH 2.5 Per1 stain for iron Autofluorescence Birefringence
Case I LP SB
Case 2 LP SB
Case 3 LP SB
Case 4 LP SB
+ + + + + +
+ + + + + +
+ + + + + +
+ + + + + +
+
+
+
+
+
-
-
-
+
I - + + *
+
+ + +
+ * +
+ +
+ -
+
+
-
+ + * -
-
-
+
+
+
+
+
+
+
+, positive; f,weak positive; -, negative; LP, lamina propria pigment; SB, spindle body pigment. D
Figure 3. Case I . Electron micrograph of spindle body in lymph node. x 20 000. Figure 4. Case I . Electron micrograph of macrophage containing melanosis pigment granules in the lamina propria of the colon. x 12 600.
Melanosis and spindle bodies
5I
large numbers in Case I . The bodies were found predominantly within the lymph node sinuses. In some instances a central, poorly-stained area was seen in the bodies (Figure I). In Case I spindle bodies were also seen in the submucosal lymphoid tissue of the colon (Figure 2). A comparison of staining reactions of the melanosis pigment and the spindle bodies in all four cases is shown in Table I . The staining reactions place both pigments within the wide group of lipofuscins (Pearse 1972). The electron microscopical appearance of the spindle bodies was essentially similar to that described previously (Doyle et al. 1973, Sieracki & Fisher 1973). The bodies were predominantly intracellular. When intracellular they occurred in macrophages and were frequently present in close relationship to the nucleus. In some examples remnants of a unit membrane were found at the periphery of the bodies, the incompleteness of the membrane probably resulting from sub-optimal fixation. Rounded electron dense areas were present within the bodies and in general the central zones were more electron dense than the peripheral zones (Figure 3). Identifiable organelles were not seen within the bodies. We believe these appearances support the suggestion that these bodies are giant lysosomes. Electron microscopy of macrophages in the lamina propria showed the melanosis pigment to consist of variable sized particles containing rounded electron dense material set in a less dense background (Figure 4).
Discussion The present results support the views of previous authors that the spindle bodies do not resemble organisms, that histochemically they contain lipofuscin and ultrastructurally they have an appearance suggesting giant lysosomes. Though the association of melanosis pigment in the colon and regional lymphoid tissue with spindle bodies in the lymphoid tissue may be coincidental we believe them to be related. It is known that, in melanosis coli, pigment may be found in the regional lymph nodes (Morson & Dawson 1972) and this was also noted in the present cases. Histochemically, the brown pigment of the spindle bodies and melanosis pigment can be considered as lipofuscins, but marked similarity of the staining reactions suggests a close relationship between these pigments within the broad group of lipofuscins. This similarity is also apparent ultrastructurally as shown in Figure 3 & 4. Thus, in melanosis coli, pigment formed in the lamina propria of the colon may pass to the regional lymphoid tissue where it lies within macrophage lysosomes and has an appearance similar to that seen in the lamina propria of the colon. We believe, however, that in certain cases coalescence of these lysosomes can occur, with the formation of giant lysosomes visible by light microscopy as spindle bodies. Whether this theory will explain the presence of spindle bodies in other sites will depend on examination of tissue drained by relevant lymph nodes for the presence of a suitable lipofuscin precursor material.
52
M .Hall and V.Eusebi
Acknowledgements We are grateful to Miss Y. Maddison and Mrs C. Eusebi for technical assistance and to Miss S. Byrne for typing the manuscript.
References BOYDJ.F. & VALENTINE J.C. (1970) Unidentified yellow bodies in human lymph nodes. Journal of’ Pathology 102, 58-60 CARTER C.J., GROSS M.A. & JOHNSON F.B. (1969) The selective staining of curious bodies in lymph nodes of patients as a means for diagnosis of sarcoid. Stain Technology 4, 1-4 DOYLE W.F., BRAHMAN H.D. & BURGESS J.H. (1973) The nature of yellow-brown bodies in Peritoneal lymph nodes. Histochemical and electron microscopic evaluation of these bodies in a case of suspected sarcoidosis. Archives of Pathology 96, 320-326 HAMAZAKI Y. (1938) Uber ein neues, saiirefeste substanz fiihrendes spindel korperschen der menschlicnen lymphdrusen. Virchows Archiv. Pathologische Anatomie 301, 490-522 MORSONB.C. & DAWSONI.M.P. (1972) Gastrointestinal Pathology, p. 586. Blackwell Scientific Publications, Oxford PEARSE A.G.E. (1972) Pigments and pigment precursors. In Histochemistry Theorerical and Applied, Volume 2 , 3rd Edition, p. 1050-1 100.Churchill Livingstone, Edinburgh SIERACKI J.C. & FISHER E.R. (1973) The cercoid nature of the so-called ‘Hamazaki-Wesenberg Bodies’. American Journal of Clinical Pathology 59, 248-253
Yellow-brown spindle bodies in mesenteric lymph nodes: a possible relationship with melanosis coli M.HALL* & V.EUSEBI Department of Histopathology, Royal Postgraduate Medical School, Hammersmith Hospital, Ducane Road, London Wr2 oHS Accepted for publication 23 September 1977 HALLM. & EUSEBIV. (1978)Histopathology
2, 47-52
Yellow-brown spindle bodies in mesenteric lymph nodes: a possible relationship with melanosis coli Four cases are described in which spindle-shaped, yellow-brown bodies were seen in the mesenteric lymph nodes of patients with melanosis coli. A comparison of the staining reactions and ultrastructural appearances of the spindle bodies and melanosis pigment suggest that they are related within the broad group of lipofuscins and that the spindle bodies are formed as a result of coalescence of lysosomes containing the pigment. Keywords: spindle bodies, lipofuscin, lymph node inclusions, melanosis coli
Introduction The occurrence of spindle-shaped, yellow-brown bodies in human lymph nodes has been known since Hamazaki’s description in 1938 (Hamazaki 1938). At one time these were thought to occur only in patients with sarcoidosis (Carter, Gross & Johnson 1969) but they are now known to occur in a variety of diseases (Boyd & Valentine 1970). Recent investigations of these bodies have shown them to consist of lipofuscin (Sieracki & Fisher 1973) and to have the ultrastructural appearance of giant lysosomes (Doyle, Brahman & Burgess 1973). We have encountered these bodies in the regional lymph nodes removed during colonic surgery in four patients in whom the colon showed coincidental melanosis coli. The similarities and possible relationship between the pigments are discussed.
Materials and methods The material examined was surgically removed formalin fixed colon and regional
* Address for correspondence and reprints: M.Hall, Department of Histopathology, St. George’s Hospital Medical School, Cranmer Terrace, Tooting, London SW17 ORE. 0309-0167/78/0100-0047$02.00 01978Blackwell Scientific Publications.
47
48
M.Hall and V.Eusebi
lymph nodes from a resected adenomatous polyp (Case I), two cases of adenocarcinoma (Cases z & 3) and one case of colonic ulceration and stricture following pelvic radiotherapy (Case 4). The presence of melanosis coli and spindle bodies in the regional lymph nodes was noted in Case I and subsequent colonic resections with melanosis pigment were examined for the presence of spindle bodies in the regional lymph nodes. Sections of paraffin wax-embedded material of each specimen were examined by the methods listed in Table I.Staining was performed by routine methods (Pearse 1972)and unstained paraffin sections were also examined in polarized light and for the presence of autofluorescence with a Leitz ultra violet microscope using BG 38 plus BG 12excitation filters and a K530 barrier filter. Portions of formalin-fixed material from Case I were post-fixed in osmium tetroxide, embedded in epon, ultrathin sections cut, stained with lead citrate and uranyl acetate and examined by electron microscopy.
Results All four cases showed melanosis coli with macrophages containing brown pigment granules present in the lamina propria of the colon. Similar pigment was present
Figure I. Case 2. Lymph node showing spindle bodies in some of which a central poorly-stained zone is seen. Schmorl x 400.
Melanosis and spindle bodies
49
Figure 2. Case I . Colon showing melanosis pigment in macrophages in lamina propria and spindle bodies (arrowed) in sub-mucosal lymphoid tissue. PAS x 400.
within macrophages in the regional lymph nodes and the staining characteristics of this pigment were identical to that in the lamina propria. Spindle bodies were present in lymph nodes in all four cases, the number present varied from scanty in Case 3 to Table r. Comparison of staining reactions of the melanosis pigment and spindle bodies
Staining method PAS PAS after diastase Schmorl Long ZN Masson-Fontana Sudan black on paraffin sections Alcian blue pH 2.5 Per1 stain for iron Autofluorescence Birefringence
Case I LP SB
Case 2 LP SB
Case 3 LP SB
Case 4 LP SB
+ + + + + +
+ + + + + +
+ + + + + +
+ + + + + +
+
+
+
+
+
-
-
-
+
I - + + *
+
+ + +
+ * +
+ +
+ -
+
+
-
+ + * -
-
-
+
+
+
+
+
+
+
+, positive; f,weak positive; -, negative; LP, lamina propria pigment; SB, spindle body pigment. D
Figure 3. Case I . Electron micrograph of spindle body in lymph node. x 20 000. Figure 4. Case I . Electron micrograph of macrophage containing melanosis pigment granules in the lamina propria of the colon. x 12 600.
Melanosis and spindle bodies
5I
large numbers in Case I . The bodies were found predominantly within the lymph node sinuses. In some instances a central, poorly-stained area was seen in the bodies (Figure I). In Case I spindle bodies were also seen in the submucosal lymphoid tissue of the colon (Figure 2). A comparison of staining reactions of the melanosis pigment and the spindle bodies in all four cases is shown in Table I . The staining reactions place both pigments within the wide group of lipofuscins (Pearse 1972). The electron microscopical appearance of the spindle bodies was essentially similar to that described previously (Doyle et al. 1973, Sieracki & Fisher 1973). The bodies were predominantly intracellular. When intracellular they occurred in macrophages and were frequently present in close relationship to the nucleus. In some examples remnants of a unit membrane were found at the periphery of the bodies, the incompleteness of the membrane probably resulting from sub-optimal fixation. Rounded electron dense areas were present within the bodies and in general the central zones were more electron dense than the peripheral zones (Figure 3). Identifiable organelles were not seen within the bodies. We believe these appearances support the suggestion that these bodies are giant lysosomes. Electron microscopy of macrophages in the lamina propria showed the melanosis pigment to consist of variable sized particles containing rounded electron dense material set in a less dense background (Figure 4).
Discussion The present results support the views of previous authors that the spindle bodies do not resemble organisms, that histochemically they contain lipofuscin and ultrastructurally they have an appearance suggesting giant lysosomes. Though the association of melanosis pigment in the colon and regional lymphoid tissue with spindle bodies in the lymphoid tissue may be coincidental we believe them to be related. It is known that, in melanosis coli, pigment may be found in the regional lymph nodes (Morson & Dawson 1972) and this was also noted in the present cases. Histochemically, the brown pigment of the spindle bodies and melanosis pigment can be considered as lipofuscins, but marked similarity of the staining reactions suggests a close relationship between these pigments within the broad group of lipofuscins. This similarity is also apparent ultrastructurally as shown in Figure 3 & 4. Thus, in melanosis coli, pigment formed in the lamina propria of the colon may pass to the regional lymphoid tissue where it lies within macrophage lysosomes and has an appearance similar to that seen in the lamina propria of the colon. We believe, however, that in certain cases coalescence of these lysosomes can occur, with the formation of giant lysosomes visible by light microscopy as spindle bodies. Whether this theory will explain the presence of spindle bodies in other sites will depend on examination of tissue drained by relevant lymph nodes for the presence of a suitable lipofuscin precursor material.
52
M .Hall and V.Eusebi
Acknowledgements We are grateful to Miss Y. Maddison and Mrs C. Eusebi for technical assistance and to Miss S. Byrne for typing the manuscript.
References BOYDJ.F. & VALENTINE J.C. (1970) Unidentified yellow bodies in human lymph nodes. Journal of’ Pathology 102, 58-60 CARTER C.J., GROSS M.A. & JOHNSON F.B. (1969) The selective staining of curious bodies in lymph nodes of patients as a means for diagnosis of sarcoid. Stain Technology 4, 1-4 DOYLE W.F., BRAHMAN H.D. & BURGESS J.H. (1973) The nature of yellow-brown bodies in Peritoneal lymph nodes. Histochemical and electron microscopic evaluation of these bodies in a case of suspected sarcoidosis. Archives of Pathology 96, 320-326 HAMAZAKI Y. (1938) Uber ein neues, saiirefeste substanz fiihrendes spindel korperschen der menschlicnen lymphdrusen. Virchows Archiv. Pathologische Anatomie 301, 490-522 MORSONB.C. & DAWSONI.M.P. (1972) Gastrointestinal Pathology, p. 586. Blackwell Scientific Publications, Oxford PEARSE A.G.E. (1972) Pigments and pigment precursors. In Histochemistry Theorerical and Applied, Volume 2 , 3rd Edition, p. 1050-1 100.Churchill Livingstone, Edinburgh SIERACKI J.C. & FISHER E.R. (1973) The cercoid nature of the so-called ‘Hamazaki-Wesenberg Bodies’. American Journal of Clinical Pathology 59, 248-253
