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Collagenous Spherulosis
Path. Res. Pract. 186,365-370 (1990)
Collagenous Spherulosis A Comment on Its Histogenesis M. Michal and A. Skalova 1 Department of Pathology, KUNZ-Plzei'l-Dobfany, CSSR. ISikl's Department of Pathology, Medical Faculty Plzei'l, CSSR
SUMMARY
Collagenous spherulosis is a benign breast lesion involving lobular acini and ductules consisting ofeosinophilic spherules measuring up to 100 !! in diameter. It is a myoepithelial product. We described similar lesions in salivary gland tumors and a benign lymphoepitheliallesion of the parotid gland.
I~troduction
Recently Clement et a1. 4 published a clinicopathologic study of a benign lesion of the breast, named collagenous spherulosis (CS) of the breast. The lesion partially or completely filled the lumina of ductules (terminal ducts), distended acini or both (Fig. 1). It consisted of focal aggregates of well circumscribed, acellular spherules that varied in size from approximately 20-100!! in diameter. The spherules were typically discrete but in most cases some of them coalesced. The number of spherules ranged from a few to approximately 50 within a given focus 4• Further, the authors claimed to see similar spherule depositions in some pleomorphic adenomas (PA) of major and minor salivary glands and in a case of polymorphous low grade adenocarcinoma of the salivary glands6 . Clement further reported about the reactivity of CS with antibodies against type IV collagen, supporting the myoepithelial origin of CS5. We reviewed salivary gland and breast tumors from the registry of pathology departments in Pilsen and Dobfany, looking for further cases of CS or similar spherule formations to prove its origin. At the same time, when reviewing the literature dealing with myoepithelias, we found that HamperF described a lesion?, undoubtedly similar, if not identical to CS. Since Hamperl described the histogenesis of these bodies in detail, we consider it worthwhile to cite several passages. © 1990 by Gustav Fischer Verlag, Sruttgart
"Once attention has been drawn to these round or ovoid inclusions, they are easily recognized even with the usual collagen stains ... The ovoid bodies may enlarge and swell; at the same time their affinity for collagen stains decreases, whereas their affinity for mucus stains is enhanced. Silver stains may then demonstrate filiform or radially arranged structures owing to a radial coagulation of the mucus. This picture matches exactly that of inclusions in a cylindroma and might even be regarded as a model of the development of rounded and otherwise shaped structures in cylindromas... The diffuse proliferation of the myothelia and their "cylindromatous transformation" may occasionally be observed in the whole of the circumference of a duct. At other times the proliferation may be purely focal, analogous to the focal hyperplasia described above. Sometimes, a small excretory duct can even become completely obliterated, so that it gives the impression of a minute cylindroma. It may also happen that the epithelium is compressed by the expanding inclusions to such an extent that it becomes necrotic and only the ovoid inclusions finally remain. Taking into account the present state of our knowledge it seems futile to argue whether these septa, intercellular filaments, and corpuscles ought to be considered as excretion products of the myothelia ..."
The similarity between CS and adenoid cystic carcinoma (ACC) as stated by HamperF and Clemenr4 is remarkable. 0344-0338/90/0186-0365$3.50/0
366 . M. Michal and A. 5kalova
Fig. 1. C5 of the breast from a 57 year old woman with infiltrating ductal carcinoma. Van Gieson stain, 160x.
Material and Methods Hyalin cylinders as frequently seen in ACC can focally attain such a structure that it can be virtually indistinguishable from C5. Hamperl's term "minute cylindroma" - like formations for C5 seems to be quite accurate. This is supported by comparing Fig. 2, taken from a case of ACe. One further tumor in which one can see similar spherules is PA. Fig. 3 is from a small tumor that arose in a skin scar in a 73 year old woman, 17 years after operation for a PA of the parotid gland. Nearly the whole tumor was composed of peculiar spherules. 5-100 protein immunoreactivity in the cells circumscribing the spherules established the myoepithelial nature of the tumor and led to a diagnosis of recurrent PA in the scar. The histogenesis of C5-like spherules can be followed in a case of PA in the parotid gland of a 30 year old woman. A considerable part of the tumor consisted of "hyalin cells" with excentric nuclei 8• Frequently, as seen in Fig. 4, these "hyalin cells" clustered together, having their nuclei turned outwardly. Their cytoplasm coalesced, forming CS-like spherules. Similar CS-like spherules were also observed in a case of monomorphous clear cell carcinoma of parotis 3 (Fig. 5).
Results When reviewing registry cases of salivary gland benign lymphoepitheliallesions, we came across a very interesting case. A 39 year old woman had a unilateral "tumor" of the parotid gland which lasted one month. Clinically, she had elevated serum titre against toxoplasmosis. Microscopically the parotid gland structure was replaced by lymphoid infiltrate with germinal centers, epimyoepithelial islands in all stages of development10 , and rests of atrophying acini. Some of the epimyoepithelial islands had structures closely resembling CS. Germinal centers with blastic appearance had uneven "moth-eaten" edges 9, invaded by epitheloid histiocytes as characteristically seen in toxoplasmic lymphadenities (Fig. 6). According to HamperF "epimyoepithelial islands of mammary gland" are lesions occurring in cases of proliferating mastopathy. It should be generally equivalent to the epitheliosis of Azzopardi's nomenclature 1 • Azzopardi's epitheliosis is an epithelial proliferation usually stretched around CS4.
Fig. 2. CS-like focus in a case of ACC of trachea from a 50 year old man. Hematoxylin and eosin stain, 400x.
Fig. 3. CS-like spherule in PA arising in a skin scar in a 73 year old woman. Hematoxylin and eosin strain, 160x.
Fig. 4. PA of parotis from 30 year old woman. The tumor consisted of "hyalin cells". In the upper left corner the hyalin cell myoepithelias cluster together (arrow) so as to form a CS-like spherule. Hematoxylin and eosin stain, 400x.
Fig. 5. Monomorphous clear cell carcinoma of the parotid gland from a 70 year old woman with CS-like spherules. Hematoxylin and eosin stain, 400x.
Fig. 6. An epimyoepithelial island in a case of benign Iymphoepitheliallesion. The islands have a structure resembling CS of the breast. Hematoxylin and eosin stain, 400 x.
Fig. 7. Spindle cells in a myoepithelioma of the parotid gland from a 53 year old man sharply delimit epimyoepithelial island -like clusters. At the edges of these clusters collagen crystalloids can frequently be observed. Hematoxylin and eosin stain, lOOx.
370 . M. Michal and A. Skalova
As the last noteworthy case we would like to mention a 53 year old man with a myoepithelioma of parotis. Most of the tumor was composed of spindle cells. These spindle cell myoepithelias sharply delineated small clusters of cells which were shaped like epimyoepithelial islands of salivary glands. These epimyoepithelial - like islands were frequently in touch with peculiar stellate fibrillar formations as described by Thackray ll in PAs (Fig. 7). Such stellate fibrillar formations were later called "collagen crystalloids" by Campbell2 . Campbell observed them especially in those PAs having a high content of "hyalin cell" myoepithelias. Even if the particular structure of collagen crystalloids is not entirely identical to CS, the histogenesis seems to be the same for both. Discussion A review of the literature and the case material presented here leads to several conclusions: 1) CS and related formations are myoepithelial products. 2) ACC can have small foci identical to CS of the breast. However, ACC can be easily differentiated from CS by an infiltrating growth pattern. 3) CS-like spherules can occur in monomorphous clear cell carcinoma, PAs, and as described by Clement et a1. 4, in the polymorphous low grade carcinoma of salivary glands6• 4) CS-like spherules in PAs can be formed by an appositive coalescence of "hyalin cell" myoepithelias. 5) Epimyoepithelial islands of salivary glands can produce CS-like collagenous bodies which can further serve as an indirect indicator of the myoepithelial origin of CS of the breast.
6) Epitheliosis of the breast l , usually seen around CS of the breast, can be histogenetically similar to epimyoepithelial islands of salivary glands.
References 1 Azzopardi JG (1979) Problems in Breast Pathology. WB Saunders Company Ltd, London-Philadelphia-Toronto 2 Campbell WG Jr, Priest RE, Weathers DR (1985) Characterization of two types of crystalloids in pleomorphic adenomas of minor salivary glands. Am J Pathol118: 194-202 3 Chan KTK (1983) Clear cell carcinoma of the salivary gland. Hum Pathol13: 91-93 4 Clement PB, Young RH, Azzopardi JG (1987) Collagenous spherulosis of the breast. Am J Surg Pathol 11: 411-417 5 Clement PB (1987) Collagenous spherulosis. A letter to the editor. Am J Surg Pathol 11: 907 6 Evans HL, Batsakis JG (1984) Polymorphous low-grade adenocarcinoma of minor salivary glands. Cancer 53: 935-942 7 Hamperl H (1970) The myothelia (Myoepithelial cells). Curr Topics Pathol 53: 161-220 8 Lomax-Smith JD, Azzopardi JG (1978) The hyalin cells: a distinctive feature of mixed salivary tumors. Histopathology 2: 77-92 9 Michal M, Koza V (1989) Blastic hyperproliferation of germinal centers with zonal arrangement-characteristic feature of toxoplasmic Iymphadenity. Path Res Pract 185: 104 10 Seifert G, Geiler G (1957) Vergleichende Untersuchungen der Kopfspeichel - und Tranendriisen zur Pathogenese des Sjogren-Syndroms und der Mikulcz-Krankheit. Virchows Archiv A (pathol Anat und Histol) 330: 402-424 11 Thackray AC, Lucas RB (1974) Tumors of the Major Salivary Glands. Atlas of Tumor Pathology, Second Series. Armed Forces Institute of Pathology, Washington DC
Received August 14, 1989 . Accepted in revised form October 24, 1989
Key Words: Collagenous spherulosis - Salivary -gland tumors - Benign lymphoepithelial lesion - Breast disease Myoepital lesions MUDr. Michal Michal, U trati 53, 320 22 Plzen, CSSR
Collagenous Spherulosis A Comment on Its Histogenesis M. Michal and A. Skalova 1 Department of Pathology, KUNZ-Plzei'l-Dobfany, CSSR. ISikl's Department of Pathology, Medical Faculty Plzei'l, CSSR
SUMMARY
Collagenous spherulosis is a benign breast lesion involving lobular acini and ductules consisting ofeosinophilic spherules measuring up to 100 !! in diameter. It is a myoepithelial product. We described similar lesions in salivary gland tumors and a benign lymphoepitheliallesion of the parotid gland.
I~troduction
Recently Clement et a1. 4 published a clinicopathologic study of a benign lesion of the breast, named collagenous spherulosis (CS) of the breast. The lesion partially or completely filled the lumina of ductules (terminal ducts), distended acini or both (Fig. 1). It consisted of focal aggregates of well circumscribed, acellular spherules that varied in size from approximately 20-100!! in diameter. The spherules were typically discrete but in most cases some of them coalesced. The number of spherules ranged from a few to approximately 50 within a given focus 4• Further, the authors claimed to see similar spherule depositions in some pleomorphic adenomas (PA) of major and minor salivary glands and in a case of polymorphous low grade adenocarcinoma of the salivary glands6 . Clement further reported about the reactivity of CS with antibodies against type IV collagen, supporting the myoepithelial origin of CS5. We reviewed salivary gland and breast tumors from the registry of pathology departments in Pilsen and Dobfany, looking for further cases of CS or similar spherule formations to prove its origin. At the same time, when reviewing the literature dealing with myoepithelias, we found that HamperF described a lesion?, undoubtedly similar, if not identical to CS. Since Hamperl described the histogenesis of these bodies in detail, we consider it worthwhile to cite several passages. © 1990 by Gustav Fischer Verlag, Sruttgart
"Once attention has been drawn to these round or ovoid inclusions, they are easily recognized even with the usual collagen stains ... The ovoid bodies may enlarge and swell; at the same time their affinity for collagen stains decreases, whereas their affinity for mucus stains is enhanced. Silver stains may then demonstrate filiform or radially arranged structures owing to a radial coagulation of the mucus. This picture matches exactly that of inclusions in a cylindroma and might even be regarded as a model of the development of rounded and otherwise shaped structures in cylindromas... The diffuse proliferation of the myothelia and their "cylindromatous transformation" may occasionally be observed in the whole of the circumference of a duct. At other times the proliferation may be purely focal, analogous to the focal hyperplasia described above. Sometimes, a small excretory duct can even become completely obliterated, so that it gives the impression of a minute cylindroma. It may also happen that the epithelium is compressed by the expanding inclusions to such an extent that it becomes necrotic and only the ovoid inclusions finally remain. Taking into account the present state of our knowledge it seems futile to argue whether these septa, intercellular filaments, and corpuscles ought to be considered as excretion products of the myothelia ..."
The similarity between CS and adenoid cystic carcinoma (ACC) as stated by HamperF and Clemenr4 is remarkable. 0344-0338/90/0186-0365$3.50/0
366 . M. Michal and A. 5kalova
Fig. 1. C5 of the breast from a 57 year old woman with infiltrating ductal carcinoma. Van Gieson stain, 160x.
Material and Methods Hyalin cylinders as frequently seen in ACC can focally attain such a structure that it can be virtually indistinguishable from C5. Hamperl's term "minute cylindroma" - like formations for C5 seems to be quite accurate. This is supported by comparing Fig. 2, taken from a case of ACe. One further tumor in which one can see similar spherules is PA. Fig. 3 is from a small tumor that arose in a skin scar in a 73 year old woman, 17 years after operation for a PA of the parotid gland. Nearly the whole tumor was composed of peculiar spherules. 5-100 protein immunoreactivity in the cells circumscribing the spherules established the myoepithelial nature of the tumor and led to a diagnosis of recurrent PA in the scar. The histogenesis of C5-like spherules can be followed in a case of PA in the parotid gland of a 30 year old woman. A considerable part of the tumor consisted of "hyalin cells" with excentric nuclei 8• Frequently, as seen in Fig. 4, these "hyalin cells" clustered together, having their nuclei turned outwardly. Their cytoplasm coalesced, forming CS-like spherules. Similar CS-like spherules were also observed in a case of monomorphous clear cell carcinoma of parotis 3 (Fig. 5).
Results When reviewing registry cases of salivary gland benign lymphoepitheliallesions, we came across a very interesting case. A 39 year old woman had a unilateral "tumor" of the parotid gland which lasted one month. Clinically, she had elevated serum titre against toxoplasmosis. Microscopically the parotid gland structure was replaced by lymphoid infiltrate with germinal centers, epimyoepithelial islands in all stages of development10 , and rests of atrophying acini. Some of the epimyoepithelial islands had structures closely resembling CS. Germinal centers with blastic appearance had uneven "moth-eaten" edges 9, invaded by epitheloid histiocytes as characteristically seen in toxoplasmic lymphadenities (Fig. 6). According to HamperF "epimyoepithelial islands of mammary gland" are lesions occurring in cases of proliferating mastopathy. It should be generally equivalent to the epitheliosis of Azzopardi's nomenclature 1 • Azzopardi's epitheliosis is an epithelial proliferation usually stretched around CS4.
Fig. 2. CS-like focus in a case of ACC of trachea from a 50 year old man. Hematoxylin and eosin stain, 400x.
Fig. 3. CS-like spherule in PA arising in a skin scar in a 73 year old woman. Hematoxylin and eosin strain, 160x.
Fig. 4. PA of parotis from 30 year old woman. The tumor consisted of "hyalin cells". In the upper left corner the hyalin cell myoepithelias cluster together (arrow) so as to form a CS-like spherule. Hematoxylin and eosin stain, 400x.
Fig. 5. Monomorphous clear cell carcinoma of the parotid gland from a 70 year old woman with CS-like spherules. Hematoxylin and eosin stain, 400x.
Fig. 6. An epimyoepithelial island in a case of benign Iymphoepitheliallesion. The islands have a structure resembling CS of the breast. Hematoxylin and eosin stain, 400 x.
Fig. 7. Spindle cells in a myoepithelioma of the parotid gland from a 53 year old man sharply delimit epimyoepithelial island -like clusters. At the edges of these clusters collagen crystalloids can frequently be observed. Hematoxylin and eosin stain, lOOx.
370 . M. Michal and A. Skalova
As the last noteworthy case we would like to mention a 53 year old man with a myoepithelioma of parotis. Most of the tumor was composed of spindle cells. These spindle cell myoepithelias sharply delineated small clusters of cells which were shaped like epimyoepithelial islands of salivary glands. These epimyoepithelial - like islands were frequently in touch with peculiar stellate fibrillar formations as described by Thackray ll in PAs (Fig. 7). Such stellate fibrillar formations were later called "collagen crystalloids" by Campbell2 . Campbell observed them especially in those PAs having a high content of "hyalin cell" myoepithelias. Even if the particular structure of collagen crystalloids is not entirely identical to CS, the histogenesis seems to be the same for both. Discussion A review of the literature and the case material presented here leads to several conclusions: 1) CS and related formations are myoepithelial products. 2) ACC can have small foci identical to CS of the breast. However, ACC can be easily differentiated from CS by an infiltrating growth pattern. 3) CS-like spherules can occur in monomorphous clear cell carcinoma, PAs, and as described by Clement et a1. 4, in the polymorphous low grade carcinoma of salivary glands6• 4) CS-like spherules in PAs can be formed by an appositive coalescence of "hyalin cell" myoepithelias. 5) Epimyoepithelial islands of salivary glands can produce CS-like collagenous bodies which can further serve as an indirect indicator of the myoepithelial origin of CS of the breast.
6) Epitheliosis of the breast l , usually seen around CS of the breast, can be histogenetically similar to epimyoepithelial islands of salivary glands.
References 1 Azzopardi JG (1979) Problems in Breast Pathology. WB Saunders Company Ltd, London-Philadelphia-Toronto 2 Campbell WG Jr, Priest RE, Weathers DR (1985) Characterization of two types of crystalloids in pleomorphic adenomas of minor salivary glands. Am J Pathol118: 194-202 3 Chan KTK (1983) Clear cell carcinoma of the salivary gland. Hum Pathol13: 91-93 4 Clement PB, Young RH, Azzopardi JG (1987) Collagenous spherulosis of the breast. Am J Surg Pathol 11: 411-417 5 Clement PB (1987) Collagenous spherulosis. A letter to the editor. Am J Surg Pathol 11: 907 6 Evans HL, Batsakis JG (1984) Polymorphous low-grade adenocarcinoma of minor salivary glands. Cancer 53: 935-942 7 Hamperl H (1970) The myothelia (Myoepithelial cells). Curr Topics Pathol 53: 161-220 8 Lomax-Smith JD, Azzopardi JG (1978) The hyalin cells: a distinctive feature of mixed salivary tumors. Histopathology 2: 77-92 9 Michal M, Koza V (1989) Blastic hyperproliferation of germinal centers with zonal arrangement-characteristic feature of toxoplasmic Iymphadenity. Path Res Pract 185: 104 10 Seifert G, Geiler G (1957) Vergleichende Untersuchungen der Kopfspeichel - und Tranendriisen zur Pathogenese des Sjogren-Syndroms und der Mikulcz-Krankheit. Virchows Archiv A (pathol Anat und Histol) 330: 402-424 11 Thackray AC, Lucas RB (1974) Tumors of the Major Salivary Glands. Atlas of Tumor Pathology, Second Series. Armed Forces Institute of Pathology, Washington DC
Received August 14, 1989 . Accepted in revised form October 24, 1989
Key Words: Collagenous spherulosis - Salivary -gland tumors - Benign lymphoepithelial lesion - Breast disease Myoepital lesions MUDr. Michal Michal, U trati 53, 320 22 Plzen, CSSR