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Spindle cell lipoma of the breast
Pathology (1999) 31, pp. 288 ± 291
SPINDLE CELL LIPOMA OF THE BREAST N IC H O L A S J. M U LVA N Y *, A LV IN G T O N C. S ILV E S T E R *
AND
J O H N P. C O L L IN S ²
Anatomical Pathology Department* and the Breast Unit², The Royal Women’s Hospital, Melbourne, Australia
Summary Spindle cell lesions, which commonly arise in the soft tissues, may present in the breast and be difficult to distinguish from primary mammary spindle cell tumors. We present the case of a 28 year old woman with a 1.5 cm circumscribed spindle cell lipoma lying deep within the tissue of the right breast. Thin, uniform spindle cells were associated with collagen bundles, mature adipocytes and entrapped normal mammary ducts, lobules, vessels and nerves, appearances which simulated an aggressively infiltrating tumor. The spindle cells proved immunoreactive to CD34 and vimentin but non-reactive for cytokeratin, S100, desmin, smooth muscle actin and Factor VIII. Although surgical resection was incomplete, the patient is alive and without evidence of tumor recurrence 12 months postoperatively. In our case, a conservative approach to management was justified and supported by the patient’s subsequent clinical course. This case exemplifies the diagnostic challenge of spindle cell lesions arising in breast tissue and the value of immunoperoxidase stains.
CASE REPORT A 29 yr old woman presented to her general practitioner complaining of a breast lump which had been first noted some 2 mo previously. On palpation a solitary, firm, freely-mobile and non-tender mass was located in the right breast. The woman was referred to a specialist breast surgeon (JPC ) who confirmed the presence of a solitary, well-circumscribed, non-tethered 2 cm mass in the right upper inner quadrant. No nipple discharge or retraction of the overlying skin was noted. Clinical examination failed to reveal any other breast lumps or any subcutaneous lesions elsewhere. On enquiry, no personal history of previously excised lipomas or family history of fatty tumors or Madelung’s disease (multiple symmetrical lipomatosis) was elicited. None of the stigmata of Gardner’s syndrome or familial multicentric fibromatosis were identified. There was no history of previous injury to the breast, trauma, FNA or surgery. The lesion could not be identified on ultrasound examination nor were any cystic changes visualized in the
Key words: M ammary lipoma, pleomorphic lipoma, spindle cell liposarcoma, fibromatosis, nodular fasciitis, diffuse neurofibromas, myoepitheliomas. Abbreviations: DFSP, dermatofibrosarcoma protuberans; SCL, spindle cell lipoma. Accepted 24 February 1999
INTRODUCTION Spindle cell lipoma (SCL), a rare variant of benign lipomas, usually occurs in the subcutaneous tissues of the upper back, posterior neck and shoulders of men older than 40 years.1 Isolated reports have described SCLs in several other sites including the oral cavity, extrem ities and deep skeletal muscle and a mammary origin was first described several years ago. 2 ± 5 The tum ors comm only present as solitary, firm, nontender masses, but multifocal lesions and an inherited tendency have been recently reported.6 Fine needle aspiration (FNA) of mammary SC Ls may produce a worrisome picture on account of isolated atypical cells, a myxoid stromal background and the absence of bipolar sentinel nuclei.4 Unlike atypical lipomas, all the reported tum ors have acted in a benign fashion. We describe here the occurrence of a SC L in a rare site, the breast, and discuss the differential diagnosis. If aware of the histological features of this lesion, a confident diagnosis can be suggested on the basis of frozen section exam ination, and further surgery avoided.
Fig. 1 The spindle cells and collagen entrap normal mammary glands and lobules and appear to irregularly dissect the adipose tissue (H & E, original magnification 390).
ISSN 0031±3025 printed/ISSN 1465-3931 online/99/030288 ± 04 1999 Royal College of Pathologists of Australasia
MAM M ARY SPINDLE C ELL LIPOM A
Fig. 2 A sm all nerve is entrapped by a tumor formed by bland spindle cells and thick collagen bundles (H & E, original magnification 3180).
adjacent tissues. The patient was referred to surgery. On exploration, an apparently well-circumscribed mass lay deep within the breast tissue. No dermal attachment was noted and the breast mass was excised. The resected surgical specimen consisted of a 3 3 2.5 3 1.2 cm mass of fatty tissue containing a circumscribed 1.5 cm, yellowish-white, partly fatty mass. No hemorrhagic or necrotic foci were seen on transection. No overlying skin was included in the specimen, nor were any axillary lymph nodes received. Frozen section examination revealed a non-encapsulated and moderately cellular lesion formed by uniform spindle cells, and a diagnosis of SC L was suggested by one of the authors (ACS). The touch impression sm ears prepared at the time of frozen section examination revealed sm all numbers of distorted spindle cells unaccompanied by any sentinel nuclei. A diagnosis of a spindle cell lesion of uncertain significance was conveyed to the surgeon. Subsequent microscopic examination of the paraffin sections revealed a poorly-circumscribed lesion consisting of short, irregular, interlacing fascicles or circumscribed micronodules of monomorphic spindle cells and collagen with focal myxoid areas (Fig. 1). The spindle cells possessed short fusiform nuclei and sm all nucleoli. No cellular atypia or mitotic activity was seen. Sm all numbers of entrapped mammary ducts and nerves were noted (Fig. 2). A single muscular walled vessel demonstrated intimal proliferation which was associated with a mild, mixed inflammatory infiltrate (Fig. 3). The spindle cells extended to the inked margins of the surgical specimen. Immunoperoxidase stain for CD34 antibody (QBEnd/10) was positive in the cytoplasm of the spindle cells, but only after antigen retrieval by trypsinization. S100 decorated the nuclei and cytoplasm of the normal fat cells and also sporadic interfascicular spindle cells. The latter did not have
289
Fig. 3 Deep within the tumor, a large muscular vessel is partly replaced by fibrous tissue, a finding of uncertain clinical significance. Note the sm all amount of residual internal elastica lamina (H & E, original magnification 390).
the morphological appearance of entrapped dendritic cells. The spindle cells were strongly immunoreactive for vimentin. Stains for cytokeratin, desmin, sm ooth muscle actin and Factor VIII were non-immunoreactive. Periodic acid-Schiff stain was non-contributory. The myxoid areas contained alcian blue-rich material which was hyaluronidase labile. The patient is alive and well at clinical follow-up 12 mo postoperatively. No local tumor recurrence or de novo breast masses were found on clinical examination.
DISCUSSION SC Ls form 1.5% of all adipocytic neoplasms, and in one series the classical lipomas were 60 times more comm on than SCLs.7 Even within SC Ls, mamm ary origin is rare and only a few acceptable cases have been previously reported in the literature (Table 1). Paradoxically, the mammary tum ors are reported to occur with equal frequency in males and females,4 although the overall incidence of SCLs is 100-fold greater in men than in wom en. SCLs present a variety of appearances on both gross and m icroscopic examination. The resected lesion may be soft or firm in consistency and either whitish-yellow, as in our case, or red in color, depending upon the relative proportions of fat, collagen and blood vessels. Lesions up
290
Pathology (1999), 31, August
MULVANY et al.
TA B L E 1 Cases of spindle cell lesions, lipomatous and lipoma-like, previously reported in the literature Number of patients (reference)
Age (yrs)
Sex
Breast laterality
4 (2) a
46 ± 83
3M, 1 F
right 3 3 c left 3 2
1 (3) a 1 (4) 1( 5) 1b
43 66 58 29
1 1 1 1
left left right right
F F M F
a The authors of the reports of these 5 patients favored the designation mammary fibroma and a fibroblast cell origin. b Present case. c One patient had bilateral spindle cell lipomas.
to 14 cm in diameter have been reported in one series, but the majority measure less than 5 cm.7 The neoplasms are described as lobulated or well circum scribed. 1 How ever, due to incomplete resection of the lesion in our patient, no smooth, well-circum scribed margin could be identified on frozen section exam ination. The histological appearances of our patient’s tum or were those of the classical SC L: a lesion of variable cellularity, containing diffusely intermixed short collagen fibres, well-aligned and unevenly distributed spindle cells of bland appearance, mature adipocytes, scattered mast cells and foci of a hyaluronic acid-rich myxoid matrix. If, as in our case, resection is incom plete, a false impression m ay be obtained of neoplastic cells aggressively infiltrating normal fat. This erroneous interpretation is due to passive adipocyte encirclem ent ªthe spindle cells transforming into fat cellsº which sim ulates the ªaggressiveº fat entrapment found in more sinister spindle cell lesions of the breast. Num erous morphological variants of SCL have been described, based upon the presence of various m etaplasias or significant alterations in the cell to stroma ratio. Cellular, palisading, pleomorphic, sclerosing, myxom atous and pseudoangiom atous variants have been recently defined with or without cartilaginous or osseous metaplasia, but none of these variants was seen in our patient’s biopsy.7 ,8 Some, but not all authors, believe that SC Ls become more cellular with time, and this might account for the developm ent of focal pleomorphic-like lipomatous changes with multinucleated floret cells and lipoblasts in otherwise classical SCLs. The histogenesis of SCLs is controversial and previous ultrastructural studies have excluded a Schwann cell origin and suggested origin from prelipoblasts or fibroblasts.3 ,5 How ever, no imm unoreactivity could be demonstrated with antibodies to M AC-387, fibronectin, laminin or type IV collagen, and current opinion favours an origin from adipocytes and/or non-fat storing, immature mesenchymal cells.9 Presumably the latter cells undergo arrested developm ent at an early stage, and the finding of S100 immunoreactivity, as in our case, supports this theory. An alternative hypothesis proposes that SC Ls belong to a broad category of mesenchymal tum ors capable of differentiation along diverse, fibroblastic, myofibroblastic, leiomyomatous and lipomatous lines. 2 The sharing of S100 and CD34 immunoreactivity in both the spindle cells and mature fat cells, as dem onstrated in our case, lends credibility to this hypoth esis, but no confirm atory ultra-
structural evidence for the existence of transitional cell form s has been found. The unusual site and young age of our patient m ay suggest a heredofamilial basis, and karyotypic rearrangements of 16q and/or 13q have been reported in SCLs/pleomorphic lipom as. 10 ,11 Unfortunately karyotypic analysis was not performed on our patient’s tum or. Nevertheless she can be reasonably assured, on the basis of our present knowledge, that she is unlikely to develop further SC Ls during the next few years. The differential diagnosis of mam mary spindle cell lesions includes a wide range of reactive, benign and malignant proliferations of the epithelium, myoepithelium and strom a, som e com mon to the dermis/subcutis but others unique to breast tissue. Uniform fibroblasts and collagen, form ing a com pact fascicular growth pattern and associated with m ammary duct/gland-entrapm ent, encircled adipocytes and low mitotic activity are features common to SCLs and fibromatosis (extraabdom inal desmoid). How ever the latter is distinguished by a stellate infiltrative margin and, in marked contrast to our case, a uniform histological pattern consisting of thin spindle cells in long sweeping fascicles. The postoperative recurrence rate of fibromatosis is 25% , while SC L rarely if ever recurs.7 ,1 2 Fibroblast-like spindle cells and collagen formation are common to SCLs and a variety of lesions which go under the rubric of inflamm atory myofibroblastic pseudotum ors. Since these reactive lesions undergo tim e-dependent m aturational changes, it is not surprising that the histological appearances can simulate granulation tissue, nodular fasciitis, fibrom atosis, fibrous histiocytoma or dense scar. The regional variation in any one lesion, polymorphou s inflamm atory infiltrate, abundant well-vascularized edematous or myxoid stroma, musclespecific and smooth m uscle actin im munoreactivity, clearly separates this lesion from the dimorphic appearance of SC L. 1 3 Both nodular fasciitis and SC Ls consist of spindle cells, but the form er has an abundan t edematous mucoid matrix, a mild focal inflam matory infiltrate, extravasated erythrocytes and mitotically active spindle cells often arranged in a zoned arrangement. Like SCL, mammary myofibroblastom a is a benign, well-circumscribed, unencapsulated tumor of spindle cells with minimal, if any, pleom orphism or mitotic activity. How ever the latter tum or, which occurs most comonly in elderly men, consists of short, intersecting acellular collagen bundles and fascicles of plump cells, with vesicular grooved nuclei demonstrating smooth m uscle a -actin and androgen-receptor im munoreactivity.1 4 Entrapped mammary ducts have been described in so-called mam mary fibrolipom as, but the m icroscopic features, in contrast to the compact spindle cell strom a in SC L, consist of a sparsely cellular fibrocollagenous stroma and entraped mature adipocytes.1 5 Adipose differentiation has been described in some phyllodes tum ors, and an epithelial cell component m ay be absent, particularly after local recurrence, but the tum or is correctly identified by the focal condensation of plump strom al cells and the lack of a fascicular growth pattern.1 6 M yoepithelial proliferative lesions of the breast are renowned for their histomorphological diversity ªspindle, plamacytoid, clear and epithelioid cell form sº necessitating the use of immunohistochemical studies in all mam mary spindle cell lesions. The spindle cell myoepithelial tumor is formed by crowded, large spindle cells forming short, interlacing bundles and demonstrating immunoreactivity with actin, cytokeratin, vimentin and S100. 17 ,1 8
M AMM ARY SPINDLE C ELL LIPOM A
Dermatofibromas are formed by a circum scribed dermal nodule of collagen and plump fibroblast-like cells immunoreactive with factor XIIIa, actin and metallothionein 19 and, unlike SCL, no fat entrapment is seen. Like dermatofibromas, derm atofibrosarcom a protuberans (DFSP) commonly arise in the dermis and rarely in subcutaneous fat. Like SC L, DFSP m ay be accompanying with ªfat entrapmentº, but this is usually extensive in the latter, comprising a lace-like pattern accom panying fascicular-storiform arrangem ent of CD34 and vim entin-positive small spindle cells. Unlike SC L, DFSP is a low grade malignant neoplasm which has been reported to recur in up to onethird of cases. 20 Not all m alignant spindle cell tumors dem onstrate cytological atypia, brisk mitotic activity and focal necrosis, as a few can appear well circum scribed and deceptively benign on microscopy yet still have an aggressive biological potential. 21 ,2 2 Cytokeratin immunoreactivity and squamous cell nests will lead to the correct diagnosis of a spindle cell carcinoma. Special mention must be made of the well-differentiated liposarcom a which occurs as a poorly-circumscribed, multinodular m ass in the subcutaneous tissues of the shoulder girdle and upper lim bs. 23 The tumors have a m ore variegated microscopic appearance than SC Ls, with lipoblasts and focal tum or necrosis, and as expected they also have a high local recurrence rate. In conclusion, m amm ary spindle cell lesions cover a wide range of pathological entities often with minimal or subtle m orpholo gical differences but great diversity in local recurrence. We believe that the SC L should enter the differential diagnosis of mammary spindle cell lesions. Although confirmatory cytogenetic analysis was not perform ed on our SC L, representative microscopic exam ination and a benign clinical course have excluded both an atypical lipoma and a spindle cell liposarcoma. The more comm on mammary spindle cell lesions, fibromatosis, DFSP, neurofibrom a and dermatofibrom a have been excluded by the immunohistochem ical panel. W hen dealing with spindle cell lesions in the breast, we recom mend the selection of an appropriate antibody panel which includes wide-spectrum cytokeratin, S100, CD34 and smooth muscle actin. Furtherm ore, we conclude that a diagnosis of SC L on frozen section examination is tentative at the best of times. A C K N O W L E D G E M E N T This case was referred to Dr I.O. Ellis at the Nottingham Breast Centre who independently offered the diagnosis of spindle cell lipom a. Address for correspondence: N.J.M., Gippsland Pathology Service, Latrobe Regional Hospital, Traralgon West, Vic 3844, Australia. E-mail: [email protected]
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References 1. Enzinger FM , Weiss SW. Soft tissue tumors. 3rd ed. St. Louis: Mosby, 1995; 395± 6. 2. Toker C, Tang C-K, Whitely JF, et al. Benign spindle cell breast tumor. Cancer 1981; 48: 1615 ± 22. 3. Chan K-W, Ghadially FN, Alagaratnam TT. Benign spindle cell tumour of breast: a variant of spindle cell lipoma or fibroma of the breast? Pathology 1984; 16: 331±7. 4. Lew W YC . Spindle cell lipoma of the breast: a case report and literature review. Diagn Cytopathol 1993; 9: 434 ±7. 5. Enzinger FM, Harvey DA. Spindle cell lipoma. Cancer 1975; 36: 1852 ± 9. 6. Fanburg-Sm ith JC , Devaney KO, M iettinen M, Weiss SW. Multiple spindle cell lipomas: a report of 7 familial and 11 nonfamilial cases. Am J Surg Pathol 1998; 22: 40 ± 8. 7. Fletcher CDM , Martin-Bates E. Spindle cell lipoma: a clinicopathological study with some original observations. Histopathology 1987; 11: 803 ±17. 8. Hawley IC, Krausz T, Evans DJ, Fletcher CDM. Spindle cell lipoma: a pseudoangiomatous variant. Histopathology 1994; 24: 565 ± 9. 9. Beham A, Schmid C, Hodl S, Fletcher CDM . Spindle cell lipoma and pleomorphic lipoma: an immunohistochemical study and histogenetic analysis. J Pathol 1989; 158: 219 ± 22. 10. M andahl N, Hoglund M, Mertens F, et al. Cytogenetic aberrations in 188 benign and borderline adipose tissue tumors. Genes, C hromosomes Cancer 1994; 9: 207±15. 11. Fletcher CDM , Akerman M, C in PD, et al. Correlation between clinicopathological features and karyotype in lipomatous tumors. A report of 178 cases from the chromosomes and morphology (CHAM P) collaborative study group. Am J Pathol 1996; 148: 623± 30. 12. Wargotz ES, Norris HJ, Austin RM , Enzinger FM . Fibromatosis of the breast: a clinical and pathological study of 28 cases. Am J Surg Pathol 1987; 11: 38 ± 45. 13. Coffin CM , Watterson J, Priest JR , Dehner LP. Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor): a clinicopathologic and immunohistochemical study of 84 cases. Am J Surg Pathol 1995; 19: 859 ±72. 14. M organ M B, Pitha JV. M yofibroblastoma of the breast revisited: an etiologic association with androgens? Hum Pathol 1998; 29: 347± 51. 15. Rosen PP. Rosen’s breast pathology Philadelphia: Lippincott-Raven, 1997; 682± 3. 16. Powell CM, Rosen PP. Adipose differentiation in cystosarcoma phyllodes. A study of 14 cases. Am J Surg Pathol 1994; 18: 720 ±7. 17. Tavassoli FA. Myoepithelial lesions of the breast. Myoepitheliosis, adenomyoepithelioma and myoepithelial carcinoma. Am J Surg Pathol 1991: 15: 554 ± 68. 18. Weidner N, Levine JD. Spindle-cell adenomyoepithelioma of the breast: a a microscopic, ultrastructural and immunocytochemical study. Cancer 1988; 62: 1561±7. 19. Zelger B, Sidoroff A, Stanzl U, et al. Deep penetrating dermatofibroma versus dermatofibrosarcoma protuberans: a clinicopathologic comparison. Am J Surg Pathol 1994; 18: 677± 86. 20. Diaz-Cascajo C , Weyers W, Rey-Lopez A, B orghi S. Deep dermatofibrosarcoma protuberans: a subcutaneous variant. Histopathology 1998; 32: 552 ±5. 21. Weidner N. Malignant breast lesions that may mimic benign tumors. Semin Diagn Pathol 1995; 12: 2±13. 22. Ruffolo EF, Maluf HM, Koerner FC. Spindle cell endocrine carcinoma of the mammary gland. Virchows Arch 1996; 428: 319 ±24. 23. Dei Tos AP, M entzel T, Newman PL, Fletcher CDM. Spindle cell liposarcoma, a hitherto unrecognised variant of liposarcoma: analysis of six cases. Am J Surg Pathol 1994; 18: 913 ± 21.
SPINDLE CELL LIPOMA OF THE BREAST N IC H O L A S J. M U LVA N Y *, A LV IN G T O N C. S ILV E S T E R *
AND
J O H N P. C O L L IN S ²
Anatomical Pathology Department* and the Breast Unit², The Royal Women’s Hospital, Melbourne, Australia
Summary Spindle cell lesions, which commonly arise in the soft tissues, may present in the breast and be difficult to distinguish from primary mammary spindle cell tumors. We present the case of a 28 year old woman with a 1.5 cm circumscribed spindle cell lipoma lying deep within the tissue of the right breast. Thin, uniform spindle cells were associated with collagen bundles, mature adipocytes and entrapped normal mammary ducts, lobules, vessels and nerves, appearances which simulated an aggressively infiltrating tumor. The spindle cells proved immunoreactive to CD34 and vimentin but non-reactive for cytokeratin, S100, desmin, smooth muscle actin and Factor VIII. Although surgical resection was incomplete, the patient is alive and without evidence of tumor recurrence 12 months postoperatively. In our case, a conservative approach to management was justified and supported by the patient’s subsequent clinical course. This case exemplifies the diagnostic challenge of spindle cell lesions arising in breast tissue and the value of immunoperoxidase stains.
CASE REPORT A 29 yr old woman presented to her general practitioner complaining of a breast lump which had been first noted some 2 mo previously. On palpation a solitary, firm, freely-mobile and non-tender mass was located in the right breast. The woman was referred to a specialist breast surgeon (JPC ) who confirmed the presence of a solitary, well-circumscribed, non-tethered 2 cm mass in the right upper inner quadrant. No nipple discharge or retraction of the overlying skin was noted. Clinical examination failed to reveal any other breast lumps or any subcutaneous lesions elsewhere. On enquiry, no personal history of previously excised lipomas or family history of fatty tumors or Madelung’s disease (multiple symmetrical lipomatosis) was elicited. None of the stigmata of Gardner’s syndrome or familial multicentric fibromatosis were identified. There was no history of previous injury to the breast, trauma, FNA or surgery. The lesion could not be identified on ultrasound examination nor were any cystic changes visualized in the
Key words: M ammary lipoma, pleomorphic lipoma, spindle cell liposarcoma, fibromatosis, nodular fasciitis, diffuse neurofibromas, myoepitheliomas. Abbreviations: DFSP, dermatofibrosarcoma protuberans; SCL, spindle cell lipoma. Accepted 24 February 1999
INTRODUCTION Spindle cell lipoma (SCL), a rare variant of benign lipomas, usually occurs in the subcutaneous tissues of the upper back, posterior neck and shoulders of men older than 40 years.1 Isolated reports have described SCLs in several other sites including the oral cavity, extrem ities and deep skeletal muscle and a mammary origin was first described several years ago. 2 ± 5 The tum ors comm only present as solitary, firm, nontender masses, but multifocal lesions and an inherited tendency have been recently reported.6 Fine needle aspiration (FNA) of mammary SC Ls may produce a worrisome picture on account of isolated atypical cells, a myxoid stromal background and the absence of bipolar sentinel nuclei.4 Unlike atypical lipomas, all the reported tum ors have acted in a benign fashion. We describe here the occurrence of a SC L in a rare site, the breast, and discuss the differential diagnosis. If aware of the histological features of this lesion, a confident diagnosis can be suggested on the basis of frozen section exam ination, and further surgery avoided.
Fig. 1 The spindle cells and collagen entrap normal mammary glands and lobules and appear to irregularly dissect the adipose tissue (H & E, original magnification 390).
ISSN 0031±3025 printed/ISSN 1465-3931 online/99/030288 ± 04 1999 Royal College of Pathologists of Australasia
MAM M ARY SPINDLE C ELL LIPOM A
Fig. 2 A sm all nerve is entrapped by a tumor formed by bland spindle cells and thick collagen bundles (H & E, original magnification 3180).
adjacent tissues. The patient was referred to surgery. On exploration, an apparently well-circumscribed mass lay deep within the breast tissue. No dermal attachment was noted and the breast mass was excised. The resected surgical specimen consisted of a 3 3 2.5 3 1.2 cm mass of fatty tissue containing a circumscribed 1.5 cm, yellowish-white, partly fatty mass. No hemorrhagic or necrotic foci were seen on transection. No overlying skin was included in the specimen, nor were any axillary lymph nodes received. Frozen section examination revealed a non-encapsulated and moderately cellular lesion formed by uniform spindle cells, and a diagnosis of SC L was suggested by one of the authors (ACS). The touch impression sm ears prepared at the time of frozen section examination revealed sm all numbers of distorted spindle cells unaccompanied by any sentinel nuclei. A diagnosis of a spindle cell lesion of uncertain significance was conveyed to the surgeon. Subsequent microscopic examination of the paraffin sections revealed a poorly-circumscribed lesion consisting of short, irregular, interlacing fascicles or circumscribed micronodules of monomorphic spindle cells and collagen with focal myxoid areas (Fig. 1). The spindle cells possessed short fusiform nuclei and sm all nucleoli. No cellular atypia or mitotic activity was seen. Sm all numbers of entrapped mammary ducts and nerves were noted (Fig. 2). A single muscular walled vessel demonstrated intimal proliferation which was associated with a mild, mixed inflammatory infiltrate (Fig. 3). The spindle cells extended to the inked margins of the surgical specimen. Immunoperoxidase stain for CD34 antibody (QBEnd/10) was positive in the cytoplasm of the spindle cells, but only after antigen retrieval by trypsinization. S100 decorated the nuclei and cytoplasm of the normal fat cells and also sporadic interfascicular spindle cells. The latter did not have
289
Fig. 3 Deep within the tumor, a large muscular vessel is partly replaced by fibrous tissue, a finding of uncertain clinical significance. Note the sm all amount of residual internal elastica lamina (H & E, original magnification 390).
the morphological appearance of entrapped dendritic cells. The spindle cells were strongly immunoreactive for vimentin. Stains for cytokeratin, desmin, sm ooth muscle actin and Factor VIII were non-immunoreactive. Periodic acid-Schiff stain was non-contributory. The myxoid areas contained alcian blue-rich material which was hyaluronidase labile. The patient is alive and well at clinical follow-up 12 mo postoperatively. No local tumor recurrence or de novo breast masses were found on clinical examination.
DISCUSSION SC Ls form 1.5% of all adipocytic neoplasms, and in one series the classical lipomas were 60 times more comm on than SCLs.7 Even within SC Ls, mamm ary origin is rare and only a few acceptable cases have been previously reported in the literature (Table 1). Paradoxically, the mammary tum ors are reported to occur with equal frequency in males and females,4 although the overall incidence of SCLs is 100-fold greater in men than in wom en. SCLs present a variety of appearances on both gross and m icroscopic examination. The resected lesion may be soft or firm in consistency and either whitish-yellow, as in our case, or red in color, depending upon the relative proportions of fat, collagen and blood vessels. Lesions up
290
Pathology (1999), 31, August
MULVANY et al.
TA B L E 1 Cases of spindle cell lesions, lipomatous and lipoma-like, previously reported in the literature Number of patients (reference)
Age (yrs)
Sex
Breast laterality
4 (2) a
46 ± 83
3M, 1 F
right 3 3 c left 3 2
1 (3) a 1 (4) 1( 5) 1b
43 66 58 29
1 1 1 1
left left right right
F F M F
a The authors of the reports of these 5 patients favored the designation mammary fibroma and a fibroblast cell origin. b Present case. c One patient had bilateral spindle cell lipomas.
to 14 cm in diameter have been reported in one series, but the majority measure less than 5 cm.7 The neoplasms are described as lobulated or well circum scribed. 1 How ever, due to incomplete resection of the lesion in our patient, no smooth, well-circum scribed margin could be identified on frozen section exam ination. The histological appearances of our patient’s tum or were those of the classical SC L: a lesion of variable cellularity, containing diffusely intermixed short collagen fibres, well-aligned and unevenly distributed spindle cells of bland appearance, mature adipocytes, scattered mast cells and foci of a hyaluronic acid-rich myxoid matrix. If, as in our case, resection is incom plete, a false impression m ay be obtained of neoplastic cells aggressively infiltrating normal fat. This erroneous interpretation is due to passive adipocyte encirclem ent ªthe spindle cells transforming into fat cellsº which sim ulates the ªaggressiveº fat entrapment found in more sinister spindle cell lesions of the breast. Num erous morphological variants of SCL have been described, based upon the presence of various m etaplasias or significant alterations in the cell to stroma ratio. Cellular, palisading, pleomorphic, sclerosing, myxom atous and pseudoangiom atous variants have been recently defined with or without cartilaginous or osseous metaplasia, but none of these variants was seen in our patient’s biopsy.7 ,8 Some, but not all authors, believe that SC Ls become more cellular with time, and this might account for the developm ent of focal pleomorphic-like lipomatous changes with multinucleated floret cells and lipoblasts in otherwise classical SCLs. The histogenesis of SCLs is controversial and previous ultrastructural studies have excluded a Schwann cell origin and suggested origin from prelipoblasts or fibroblasts.3 ,5 How ever, no imm unoreactivity could be demonstrated with antibodies to M AC-387, fibronectin, laminin or type IV collagen, and current opinion favours an origin from adipocytes and/or non-fat storing, immature mesenchymal cells.9 Presumably the latter cells undergo arrested developm ent at an early stage, and the finding of S100 immunoreactivity, as in our case, supports this theory. An alternative hypothesis proposes that SC Ls belong to a broad category of mesenchymal tum ors capable of differentiation along diverse, fibroblastic, myofibroblastic, leiomyomatous and lipomatous lines. 2 The sharing of S100 and CD34 immunoreactivity in both the spindle cells and mature fat cells, as dem onstrated in our case, lends credibility to this hypoth esis, but no confirm atory ultra-
structural evidence for the existence of transitional cell form s has been found. The unusual site and young age of our patient m ay suggest a heredofamilial basis, and karyotypic rearrangements of 16q and/or 13q have been reported in SCLs/pleomorphic lipom as. 10 ,11 Unfortunately karyotypic analysis was not performed on our patient’s tum or. Nevertheless she can be reasonably assured, on the basis of our present knowledge, that she is unlikely to develop further SC Ls during the next few years. The differential diagnosis of mam mary spindle cell lesions includes a wide range of reactive, benign and malignant proliferations of the epithelium, myoepithelium and strom a, som e com mon to the dermis/subcutis but others unique to breast tissue. Uniform fibroblasts and collagen, form ing a com pact fascicular growth pattern and associated with m ammary duct/gland-entrapm ent, encircled adipocytes and low mitotic activity are features common to SCLs and fibromatosis (extraabdom inal desmoid). How ever the latter is distinguished by a stellate infiltrative margin and, in marked contrast to our case, a uniform histological pattern consisting of thin spindle cells in long sweeping fascicles. The postoperative recurrence rate of fibromatosis is 25% , while SC L rarely if ever recurs.7 ,1 2 Fibroblast-like spindle cells and collagen formation are common to SCLs and a variety of lesions which go under the rubric of inflamm atory myofibroblastic pseudotum ors. Since these reactive lesions undergo tim e-dependent m aturational changes, it is not surprising that the histological appearances can simulate granulation tissue, nodular fasciitis, fibrom atosis, fibrous histiocytoma or dense scar. The regional variation in any one lesion, polymorphou s inflamm atory infiltrate, abundant well-vascularized edematous or myxoid stroma, musclespecific and smooth m uscle actin im munoreactivity, clearly separates this lesion from the dimorphic appearance of SC L. 1 3 Both nodular fasciitis and SC Ls consist of spindle cells, but the form er has an abundan t edematous mucoid matrix, a mild focal inflam matory infiltrate, extravasated erythrocytes and mitotically active spindle cells often arranged in a zoned arrangement. Like SCL, mammary myofibroblastom a is a benign, well-circumscribed, unencapsulated tumor of spindle cells with minimal, if any, pleom orphism or mitotic activity. How ever the latter tum or, which occurs most comonly in elderly men, consists of short, intersecting acellular collagen bundles and fascicles of plump cells, with vesicular grooved nuclei demonstrating smooth m uscle a -actin and androgen-receptor im munoreactivity.1 4 Entrapped mammary ducts have been described in so-called mam mary fibrolipom as, but the m icroscopic features, in contrast to the compact spindle cell strom a in SC L, consist of a sparsely cellular fibrocollagenous stroma and entraped mature adipocytes.1 5 Adipose differentiation has been described in some phyllodes tum ors, and an epithelial cell component m ay be absent, particularly after local recurrence, but the tum or is correctly identified by the focal condensation of plump strom al cells and the lack of a fascicular growth pattern.1 6 M yoepithelial proliferative lesions of the breast are renowned for their histomorphological diversity ªspindle, plamacytoid, clear and epithelioid cell form sº necessitating the use of immunohistochemical studies in all mam mary spindle cell lesions. The spindle cell myoepithelial tumor is formed by crowded, large spindle cells forming short, interlacing bundles and demonstrating immunoreactivity with actin, cytokeratin, vimentin and S100. 17 ,1 8
M AMM ARY SPINDLE C ELL LIPOM A
Dermatofibromas are formed by a circum scribed dermal nodule of collagen and plump fibroblast-like cells immunoreactive with factor XIIIa, actin and metallothionein 19 and, unlike SCL, no fat entrapment is seen. Like dermatofibromas, derm atofibrosarcom a protuberans (DFSP) commonly arise in the dermis and rarely in subcutaneous fat. Like SC L, DFSP m ay be accompanying with ªfat entrapmentº, but this is usually extensive in the latter, comprising a lace-like pattern accom panying fascicular-storiform arrangem ent of CD34 and vim entin-positive small spindle cells. Unlike SC L, DFSP is a low grade malignant neoplasm which has been reported to recur in up to onethird of cases. 20 Not all m alignant spindle cell tumors dem onstrate cytological atypia, brisk mitotic activity and focal necrosis, as a few can appear well circum scribed and deceptively benign on microscopy yet still have an aggressive biological potential. 21 ,2 2 Cytokeratin immunoreactivity and squamous cell nests will lead to the correct diagnosis of a spindle cell carcinoma. Special mention must be made of the well-differentiated liposarcom a which occurs as a poorly-circumscribed, multinodular m ass in the subcutaneous tissues of the shoulder girdle and upper lim bs. 23 The tumors have a m ore variegated microscopic appearance than SC Ls, with lipoblasts and focal tum or necrosis, and as expected they also have a high local recurrence rate. In conclusion, m amm ary spindle cell lesions cover a wide range of pathological entities often with minimal or subtle m orpholo gical differences but great diversity in local recurrence. We believe that the SC L should enter the differential diagnosis of mammary spindle cell lesions. Although confirmatory cytogenetic analysis was not perform ed on our SC L, representative microscopic exam ination and a benign clinical course have excluded both an atypical lipoma and a spindle cell liposarcoma. The more comm on mammary spindle cell lesions, fibromatosis, DFSP, neurofibrom a and dermatofibrom a have been excluded by the immunohistochem ical panel. W hen dealing with spindle cell lesions in the breast, we recom mend the selection of an appropriate antibody panel which includes wide-spectrum cytokeratin, S100, CD34 and smooth muscle actin. Furtherm ore, we conclude that a diagnosis of SC L on frozen section examination is tentative at the best of times. A C K N O W L E D G E M E N T This case was referred to Dr I.O. Ellis at the Nottingham Breast Centre who independently offered the diagnosis of spindle cell lipom a. Address for correspondence: N.J.M., Gippsland Pathology Service, Latrobe Regional Hospital, Traralgon West, Vic 3844, Australia. E-mail: [email protected]
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