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Leiomyoma of the uterus showing skeletal muscle differentiation: A case report
HUMAN PATHOLOGY
Volume 30, No. 3 (March 1999)
L E I O M Y O M A OF THE UTERUS S H O W I N G SKELETAL MUSCLE DIFFERENTIATION: A CASE REPORT ADELE FORNELLI, MD, G ~ A N D R ~ PASQUINELLI,MD, ANI) VINCENZOEUSEBI, MD, FRCPATH
A case of uterine leiomyoma with skeletal muscle differentiation is described. The patient is a 40-year-old woman who underwent abdominal hysterectomy and left salpingo-oophorectomy for fibroids. Evidence of skeletal muscle differentiation was evident at light and electron microscopy in one out of three "ordinary" leiomyomas. This was also shown by positive immunoreactious with antiskeletal muscle actin and myoglobin antisera. To our knowledge, this is the second
TABLE 1.
Antibody Vimentin Smooth muscle actin Skeletal muscle actin Desmin Myoglobin Calponin Caldesmon
case reported of the occurrence of skeletal muscle differentiation within a uterine leiomyoma and highlights the divergent differentiating potential of smooth muscle cells. H u ~ PATnOL 30:356-359. Copyright © 1999 byW.B. Saunders Company Key words: leiomyoma, uterus, skeletal muscle differentiation. Abbreviations: H & E, hematoxylin and eosin; ABC, avidin-biotinperoxidase; ESN, endometrial stromal nodule.
Listof Antibodies Used
Monoclonal/ Policlonal (M/P)
Dilution
M
1:200
Dako
V9
M
1:100
Dako
1A4
M M P M M
1:20 1:500 1:1200 1:80 1:80
Dako Dako Dako Biogenex Biogenex
alpha Sr-1 D-33
Source
Clone
CALP h-CD
Note. Source locations: Dako, Carpinteria, CA; Biogenex, San Ramon, CA.
Skeletal muscle differentiation has occasionally been observed within smooth muscle turnouts, 1-5 and was interpreted either as a metaplasfic p h e n o m e n o n in response of metabolic changes I or as a divergent differentiation of neoplastic cells. 5 Here we describe a case of skeletal muscle differentiation occurring in a benign leiomyoma of the uterus, studied by immunohistochemical and ultrastructural methods. The possible differential diagnoses are also discussed. CASE REPORT A 40-year-old woman presented with a 10-month history of abdominal discomfort and recurrent menometrorrhagia. Clinical and ultrasonographic examinations revealed an enlarged uterus measuring 10 × 10 × 7 cm. Abdominal hysterectomy with left salpingo-oophorectomy was performed. The patient is otherwise in good health.
FIGURE I. Small loci of ribbon-like and polygonal elements with abundant cytoplasm are present within the spindleshaped cell proliferation. (H&E, original magnification x75).
smooth muscle actin and skeletal muscle actin, and antismooth muscle actin and myoglobin were performed using alcaline phosphatase as a second tracer in addition to the ABC peroxidase method. For electron microscopy formalin-fixed tumor samples were postfixed in 1% osmium tetroxide, dehydrated in ethanol and embedded in araldite. Thin sections stained with uranyl acetate and lead citrate were examined with a Philips 400T trasmission electron microscope (Eindhoven, The Netherlands).
MATERIAL AND METHODS Tissue was fixed in 10% buffered formalin and routinely processed. Sections were stained with hematoxylin and eosin (H&E). For immunohistochemistry the avidin-biotin-peroxidase complex (ABC) was followed when a single antiserum was used. The an tibodies used and their respective sources are listed in Table 1. Combined immunoreactions using antiFrom the Department of Oncology, Section of Anatomic Pathology, Ospedale Bellaria, University of Bologna, Italy and the Institute of Electron Microscopy, Ospedale S. Orsola, University of Bologna, Italy. Address correspondence and reprint requests to Vincenzo Eusebi, MD, FRCPath, Sezione di Anatomia, Istologia e Citologia Patologica, Ospedale BeUaria,Via Altura 3, 40139 Bologna, Italy. Copyright © 1999 by W.B. Saunders Company 0046-8177/99/3003-0018510.00/0
356
FIGURE 2. At higher magnifications globoid to elongated elements are clearly visible. (H&E, original magnification x 175).
CASE STUDIES
Myoglobin positivity is intense in the globoid and elongated cells. (ABC, original magnification × 175).
FIGURE 3.
PATHOLOGICAL FINDINGS Gross Features
A hysterectomy and left salpingo-oophorectomy specimen was received. The uterus was enlarged and measured 10 cm between the cornua, l0 cm from fundus to os, and 7 cm along the anterior-posterior diameter. The myometrium showed two intramural nodules with well-circumscribed margins, measuring 5.5 and 3 cm in maximum axis. A submucosal nodule, 1.8 cm across, was also present. The cut surface of all nodules was white and with a whirled appearance.
fascicles of spindle-shaped cells with eosinophilic cytoplasm and blunt ended nuclei. In one small area there were ribbon-like elongated cells with a b u n d a n t eosinophilic cytoplasm and from one to several nuclei located beneath the plasmalemmal membrane (Figs 1, 2). Cytoplasmic crossstriations were also easily observed. Some cells were polygonal and nuclei were located at the periphery of the cell. Nuclei were r o u n d to oval and displayed prominent nucleoli. No mitoses nor necrotic areas were visible. At immunohistochemistry, the ribbon-like and polygonal cells strongly reacted with antiskeletal muscle actin and myoglobin antisera (Figs 3,4) and were weakly positive with antidesmin antiserum. Antivimentin, smooth muscle actin, calponin, and caldesmon anfisera all gave negative results in these cells. In contrast, the spindle-shaped cells, which constituted the major part of the lesion, were reactive with tile latter antisera as well as with anfidesmin antiserum and consistently negative with skeletal muscle acfin and myoglobin anfisera. The endometrium was proliferative, the cervix and left adnexum were within normal limits. At electron microscopy, focal collections of well-differentiated skeletal muscle elements, sometimes having multiple nuclei, were seen. In the cytoplasm, haphazardly arranged rudimentary sarcomeres, Z-discs of varying sizes and shapes as well as dense masses of tangled myofilaments and ribosomes could be observed (Fig 5). A continuous external lamina was a frequent finding. DISCUSSION The lesion described here is predominantly composed of fascicles of spindle-shaped cells with eosinophilic cytoplasm and blunt-ended nuclei, which show no evidence of atypia or mitotic activity and are positive with antivimentin, smooth muscle actin, calponin, caldesmon, and desmin antisera. A second minor component is constituted by ribbon-like and polygonal cells with a b u n d a n t eosinophilic cytoplasm in which cross-striations are easily visible and multiple oval to round nuclei are present. The latter elements also lack
MICROSCOPIC FINDINGS Histological examination of the submucosal and largest intramural nodule showed benign smooth muscle cell proliferation, consistent with the diagnosis of classical leiomyoma. The third nodule appeared more cellular, composed of
FIGURE 4. Antiskeletal muscle actin antiserum (brown) highlights cytoplasmic cross striations, whereas anti smooth muscle actin antiserum (red) decorates smooth muscle cells. (ABC-AP, original magnification x350).
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HUMAN PATHOLOGY
Volume 30, No. 3 (March 1999)
FIGURE 5. A globoid ceil showing cytoplasmic sarcomeres which show well formed Z-disks (inset). (IEM, original magnification x9,000; inset: original magnification x 15,000).
n u c l e a r atypia as well as mitotic activity. O n i m m u n o h i s t o c h e m istry these cells are positive with a n t i d e s m i n , skeletal m u s c l e acfin, a n d m y o g l o b i n antisera. Ultrastructurally, they show a c o n t i n u o u s e x t e r n a l lamina, r u d i m e n t a r y sarcomeres, a n d Z-discs, w h i c h i n d i c a t e skeletal m u s c l e differentiation. All t h e s e features are c o n s i s t e n t with t h e diagnosis o f l e i o m y o m a with skeletal muscle differentiation. This neop l a s m s h o u l d b e d i f f e r e n t i a t e d f r o m symplastic a n d epithelioid l e i o m y o m a a n d e n d o m e t r i a l stromal n o d u l e (ESN) with skeletal muscle differentiation. Symplastic l e i o m y o m a is characterized by a m o r e m a r k e d n u c l e a r p l e o m o r p h i s m a n d m a y show r n u l f i n u c l e a t e d g i a n t cells6; e p i t h e l i o i d l e i o m y o m a is c o m p o s e d o f r o u n d to p o l y g o n a l cells h a v i n g a b u n d a n t a n d g r a n u l a r cytoplasm with centrally located nucleus, 6 B o t h types of lesion, however, lack cytoplasmic cross-striations; i n addition, i m m u n o r e a c t i v i t y for skeletal m u s c l e actin a n d myoglob i n has n e v e r b e e n r e p o r t e d . 7 ESN with skeletal m u s c l e d i f f e r e n t i a t i o n is a r e c e n t l y d e s c r i b e d entity 8 c o m p o s e d o f e n d o m e t r i a l stromal cells i n t e r m i n g l e d with s m o o t h a n d skeletal muscle c o m p o n e n t s a n d epithelial-like s t r u c t u r e s r e m i n i s c e n t o f sex-cord elements. T h e n e o p l a s m also shows a n a r b o r i z i n g vascular p a t t e r n with vessels similar to t h e spiral arteries o f t h e m i d p r o l i f e r a t i v e e n d o m e t r i u m . This type o f vascularization as well as epithelial-like s t r u c t u r e s are lacking in t h e p r e s e n t lesion. Skeletal muscle d i f f e r e n t i a t i o n h a s b e e n o b s e r v e d w i t h i n a u t e r i n e l e i o m y o m a 1 a n d l e i o m y o s a r c o m a 24 a n d in a u n i q u e case o f r e t r o p e r i t o n e a l leiomyosarcoma. 5 T h e i n t e r p r e t a t i o n o f this p h e n o m e n o n is d e b a t a b l e . W h e n it occurs in a u t e r i n e tumor, it c a n b e c o n s i d e r e d as t h e p h e n o t y p i c e x p r e s s i o n of t h e m u l t i p l e d i f f e r e n t i a t i n g p o t e n tial o f u t e r i n e s m o o t h muscle ceils w h i c h have a Mfillerian origin. Nevertheless, skeletal muscle d i f f e r e n t i a t i o n has also b e e n o b s e r v e d in b e n i g n a n d m a l i g n a n t t u m o u r s w h i c h d i d n o t have e i t h e r m u s c u l a r o r Mfillerian origin, s u c h as sarcomatoid c a r c i n o m a s o f various organs, 91s s e m i n o m a s , 14 m e d u l l o blastomas, 1~-16 liposarcomas, 17 T r i t o n t u m o u r , 18 p l e o m o r p h i c a d e n o m a o f salivary glands,X9 n e u r o e n d o c r i n e t u m o u r s , 2° a n d a variety of n o n g e r m cell tumors. 21 To this list, t h e case o f
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l e i o m y o s a r c o m a o f r e t r o p e r i t o n e u m with r h a b d o m y o b l a s t i c d i f f e r e n t i a t i o n has to b e a d d e d . T h e r e f o r e this p h e n o m e n o n is n o t exclusive to tissues h a v i n g a Mflllerian origin a n d s h o u l d p r o b a b l y b e c o n s i d e r e d as t h e c o n s e q u e n c e of a n a b e r r a n t g e n o m i c d e r e g u l a t i o n w h i c h occurs in neoplastic cells, regardless of t h e i r origin. Skalli a n d G a b b i a n i 22 have s h o w n t h a t s m o o t h muscle cells s h a r e a c o m m o n d e v e l o p i n g pathway with skeletal m u s c l e fibers. T h e r e f o r e it is possible t h a t r h a b d o m y o b l a s t i c e l e m e n t s o b s e r v e d within a s m o o t h m u s c l e cell p r o l i f e r a t i o n , w h e r e v e r localized, are t h e p r o d u c t o f a n o m a l o u s p r o l i f e r a t i o n a l o n g t h e s a m e s t e m line. I r r e s p e c t i v e o f t h e i r o r i g i n , t h e p r e s e n c e o f welld i f f e r e n t i a t e d skeletal muscle e l e m e n t s within a l e i o m y o m a has to b e t a k e n in c o n s i d e r a t i o n in o r d e r to avoid fallacious diagnoses of m a l i g n a n t c o n d i t i o n s .
REFERENCES 1. Martin-ReayDG, Christ ML, LaPata RE: Uterine leiomyoma with skeletal muscle differentiation. AmJ Clin Patho196:344-347, 1991 2. Spirt RH, Koss LG: Myosarcomaof the uterus. Cancer 18:571-588, 1995 3. Hendrickson MR, Kempson RL: Surgical pathology of the uterine corpus, in BenningtonJL (ed): Major Problems in Pathology,Vol. 12. Philadelphia, WB Saunders, p 487, 1980 4. Stout AP: Mesenchyraoma, the mixed tumour of mesenchymal derivafives.Ann Surg 127:278-290, 1948 5. Roncaroli F, Eusebi V: Rhabdomyoblasfic differentiation in a leiomyosarcoma of the retroperitoneum. HuM PATHOL27:310-313, 1996 6. Silverberg SG, Kurman RJ: Atlas of Tumor Pathology. Tumors of the uterine corpus and gestafional trophoblasfic disease. Third series. Fascicle 3. Washington DC, Armed Forced Institute of Pathology. 1991 7. Kurman RJ, Norris HJ: Mesenchymal tumors of the uterus. VI. Epithelioid smooth muscle tumors including leiomyoblastoma and clear cell leiomyoma. A clinical and pathologic analysis of 26 cases, Cancer 37:1853-1856, 1976 8. LloretaJ, PratJ: Endometrial stromal nodule with smooth and skeletal muscle components simulating stromal sarcoma. IntJ Gynecol Pathol 11:293298, 1992 9. Foschini MP, Dina RE, Eusebi V: Sarcomatoid neoplasm of the breast:
BOOK REVIEW Proposed definition for biphasic and monophasic sarcomatoid mammary carcinomas. Sere Diagn Pathol 10:128-136, 1993 10. Goldman RL, Weidner N: Pure squamous cell carcinoma of the larynx with cervical nodal metastases showing rhabdomyosarcomatous differentiation. AmJ Surg Pathol 17:415-421, 1993 11. Humphrey PA, Scroggs M, Roggli VL, et ah Pulmonary carcinoma with a sarcomatoid component. HuM PATHOL19:155-165, 1988 12. Lauwers GY, Scevchuk M, Armenakas N, et al: Carcinosarcoma of the prostate. AmJ Surg Pathol 17:342-349, 1993 13. Snorer DC, Levine DG, RosaiJ: Thymic carcinoma. Am J Surg Pathol 6:451-470, 1982 14. True LD, Otis CN, Delprado V, etal: Spermatocytic seminoma of testis with sarcomatous trasformation. PanJ Surg Pathol 12:1166-1170, 1988 15. Smith TW, DavidsonRI: Medunomyoblastoma.A histologic, histochemica1 and ultrastructural study. Cancer 54:323-332, 1984 16. Rao C, Friedlander ME, Klein E, et al: Medullomyoblastoma in an adult. Cancer 65:157-163, 1990
17. Tallini G, Parham DM, Dias P, et al: Myogenic regulatory protein expression in adult soft tissue sarcomas. AmJ Pathol 144:693-701, 1994 18. Azzopardi GJ, Eusebi V, Tison V, et al: Neurofibroma with rhabdomyomatous differentiation: Benign "Triton" turnout of the vagina. Histopathology 7:561-572, 1983 19. Lam PWA, Chan JKC, Sin W-C: Nasal pleomorphic adenoma with skeletal muscle differentiation: Potential misdiagnosis as rhabdomyosarcoma. HuM PATHOL28:1299-1302, 1997 20. Roncaroli F, Montironi R, Feliciotti F, et al: Sarcomatoid carcinoma of the anorectal junction with neuroendocrine and rhabdomyoblastic features. AmJ Surg Pathol 19:217-223, 1995 21. Woodruff JM, Perino G: Non-germ-cell or teratomatous malignant mmours showing additional rhabdomyoblastic differentiation, with emphasis on the malignant Triton mmour. Sere Diagn Pathol 11:69-81, 1994 22. SkaUiO, Gabbiani G, Bahai F, et ah Intermediate filament proteins and actin isoforms as markers of soft tissue tumor differentiation and origin. II Rhabdomyosarcomas.AmJ Pathol 130:515-531, 1988
BOOK REVIEW Handbook o f Forensic Pathology, V i n c e n t J.M. DiMaio, S u z a n n a E. Dana. Austin, Tx, L a n d e s B i o s c i e n c e / V a d e m e c u m , 1998, 249 pages, $45.00.
i n f o r m a t i o n will find t h e references up-to-date a n d c o m p r e h e n sive. Given r e g i o n a l a n d o t h e r variations in forensic practice, individual r e a d e r s will n o d o u b t find areas o f p r o c e d u r a l a n d t h e o r e t i c a l d i s a g r e e m e n t with the a u t h o r s , for e x a m p l e in t h e i r practice o f m a r k i n g bullets, w h i c h is by n o m e a n s universal. This is n o t a weakness o f t h e text, w h i c h by necessity is b a s e d o n t h e e x p e r i e n c e o f t h e c o a u t h o r s . T h e y are careful to n o t e in t h e Preface t h a t "variations will o c c u r " f r o m t h e m o s t c o m m o n findings. This b o o k is s u p e r i o r a m o n g g e n e r a l forensic p a t h o l o g y texts i n its e m p h a s i s o n p r o c e d u r e s , w h i c h equals t h a t in forensic investigation h a n d b o o k s written for m e d i c a l investigation a n d law e n f o r c e m e n t audiences. T h e c h a p t e r s o n Physical E v i d e n c e a n d I d e n t i f i c a t i o n o f R e m a i n s are particularly welcome. T h e greatest s t r e n g t h o f this work is its u n c o m p r o m i s i n g a d h e r e n c e to scientific p r i n c i p l e s u n d e r l y i n g m o d e r n forensic p a t h o l o g y practice. It will p r o v e m o s t h e l p f u l to r e s i d e n t s a n d fellows in t r a i n i n g at m e d i c a l e x a m i n e r s ' offices a n d to m e d i c a l s t u d e n t s d e s i r i n g e x p o s u r e to t h e growing field of forensic pathology. Because o f its concise f o r m a t , d e p t h , a n d well-chosen references, it will also b e o f use to t h e p r a c t i s i n g m e d i c a l e x a m i n e r in t h e investigation o f i n f r e q u e n t l y e n c o u n t e r e d deaths, such as electrocutions.-CAROLYN H. REVERCOMB, MD, Assistant Medieal Examine,; Medical Examiner's Office, City of
T h e stated p u r p o s e o f this b o o k is to p r o v i d e a t r a i n i n g m a n u a l in forensic p a t h o l o g y for m e d i c a l students, residents, a n d fellows. T h e e m p h a s i s is o n basic principles o f forensic pathology, i n c l u d i n g t h e basis f o r forensic autopsy p r o c e d u r e , a n d o n c o m m o n f i n d i n g s in t h e variety o f d e a t h s e n c o u n t e r e d by m e d i c a l e x a m i n e r s . T h e spiral b o u n d f o r m a t , small type, a n d r e l i a n c e o n text over b l a c k a n d white illustrations recall t h e W a s h i n g t o n M a n u a l series. W h e r e p h o t o g r a p h s a n d d i a g r a m s d o a p p e a r they are effective. T h e r e are 20 c h a p t e r s w h i c h r a n g e i n l e n g t h f r o m 2 pages ( I n t r a o p e r a t i v e D e a t h s ) to 30 pages (Natural Disease, B l u n t Force Injury, G u n s h o t W o u n d s ) . Because t h e divisions are o u t l i n e d o n t h e b a c k cover, a n i n f o r m e d r e a d e r c a n find m o s t i n f o r m a t i o n quickly w i t h o u t t h e aid o f t h e seven-page index. T h e a u t h o r s s u c c e e d i n d e s c r i b i n g m a n y of t h e m o r e c o m p l e x areas of forensic pathology, i n c l u d i n g asphyxia, t h e r m a l injuries, a n d b l u n t t r a u m a , with u n u s u a l clarity a n d d e p t h . T h e r a n g e o f m a t e r i a l c o v e r e d is ambitious, a n d it is t h e r e f o r e n o t s u r p r i s i n g t h a t t h e e l a b o r a t i o n o f s o m e specialized subjects, such as i n t e r p r e t a t i o n o f findings in forensic toxicology, is relatively thin. However, those d e s i r i n g f u r t h e r
Philadelphia, Philadelphia, PA
CORRESPONDENCE Letter to the Editor
the p a t h o g e n e s i s o f m y o f i b r o b l a s t o m a . T h e i r o b s e r v a t i o n s a p p e a r to p r o v i d e a n i m p o r t a n t piece o f t h e puzzle, b u t t h e cellular substrate involved in t h e f o r m a t i o n o f myofibroblast o m a was is a d d r e s s e d only historically. We are s t u d y i n g two subsets o f strornal d e n d r i t i c cells: u n c o m m i t t e d fibroblasts t h a t express t h e p r o g e n i t o r cell a n t i g e n CD34 a n d histiocytes t h a t express c o a g u l a t i o n factor XIIIa. T h e s e u b i q u i t o u s cells a p p e a r to i n t e r a c t d u r i n g stromal m o r p h o g e n e s i s a n d in t h e
To the Editon'---We r e a d with i n t e r e s t t h e article by Drs. M o r g a n a n d P i t h a 1 r e p o r t i n g e x p r e s s i o n o f a n d r o g e n receptors in five m a m m a r y m y o f i b r o b l a s t o m a s in b o t h sexes. T h e y also s t u d i e d o t h e r s p i n d l e cell t u m o r s t h a t d i d n o t express a n d r o g e n receptor. T h e a u t h o r s state t h a t despite d e t a i l e d k n o w l e d g e o f c l i n i c o p a t h o l o g i c features, little is k n o w n a b o u t
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Volume 30, No. 3 (March 1999)
L E I O M Y O M A OF THE UTERUS S H O W I N G SKELETAL MUSCLE DIFFERENTIATION: A CASE REPORT ADELE FORNELLI, MD, G ~ A N D R ~ PASQUINELLI,MD, ANI) VINCENZOEUSEBI, MD, FRCPATH
A case of uterine leiomyoma with skeletal muscle differentiation is described. The patient is a 40-year-old woman who underwent abdominal hysterectomy and left salpingo-oophorectomy for fibroids. Evidence of skeletal muscle differentiation was evident at light and electron microscopy in one out of three "ordinary" leiomyomas. This was also shown by positive immunoreactious with antiskeletal muscle actin and myoglobin antisera. To our knowledge, this is the second
TABLE 1.
Antibody Vimentin Smooth muscle actin Skeletal muscle actin Desmin Myoglobin Calponin Caldesmon
case reported of the occurrence of skeletal muscle differentiation within a uterine leiomyoma and highlights the divergent differentiating potential of smooth muscle cells. H u ~ PATnOL 30:356-359. Copyright © 1999 byW.B. Saunders Company Key words: leiomyoma, uterus, skeletal muscle differentiation. Abbreviations: H & E, hematoxylin and eosin; ABC, avidin-biotinperoxidase; ESN, endometrial stromal nodule.
Listof Antibodies Used
Monoclonal/ Policlonal (M/P)
Dilution
M
1:200
Dako
V9
M
1:100
Dako
1A4
M M P M M
1:20 1:500 1:1200 1:80 1:80
Dako Dako Dako Biogenex Biogenex
alpha Sr-1 D-33
Source
Clone
CALP h-CD
Note. Source locations: Dako, Carpinteria, CA; Biogenex, San Ramon, CA.
Skeletal muscle differentiation has occasionally been observed within smooth muscle turnouts, 1-5 and was interpreted either as a metaplasfic p h e n o m e n o n in response of metabolic changes I or as a divergent differentiation of neoplastic cells. 5 Here we describe a case of skeletal muscle differentiation occurring in a benign leiomyoma of the uterus, studied by immunohistochemical and ultrastructural methods. The possible differential diagnoses are also discussed. CASE REPORT A 40-year-old woman presented with a 10-month history of abdominal discomfort and recurrent menometrorrhagia. Clinical and ultrasonographic examinations revealed an enlarged uterus measuring 10 × 10 × 7 cm. Abdominal hysterectomy with left salpingo-oophorectomy was performed. The patient is otherwise in good health.
FIGURE I. Small loci of ribbon-like and polygonal elements with abundant cytoplasm are present within the spindleshaped cell proliferation. (H&E, original magnification x75).
smooth muscle actin and skeletal muscle actin, and antismooth muscle actin and myoglobin were performed using alcaline phosphatase as a second tracer in addition to the ABC peroxidase method. For electron microscopy formalin-fixed tumor samples were postfixed in 1% osmium tetroxide, dehydrated in ethanol and embedded in araldite. Thin sections stained with uranyl acetate and lead citrate were examined with a Philips 400T trasmission electron microscope (Eindhoven, The Netherlands).
MATERIAL AND METHODS Tissue was fixed in 10% buffered formalin and routinely processed. Sections were stained with hematoxylin and eosin (H&E). For immunohistochemistry the avidin-biotin-peroxidase complex (ABC) was followed when a single antiserum was used. The an tibodies used and their respective sources are listed in Table 1. Combined immunoreactions using antiFrom the Department of Oncology, Section of Anatomic Pathology, Ospedale Bellaria, University of Bologna, Italy and the Institute of Electron Microscopy, Ospedale S. Orsola, University of Bologna, Italy. Address correspondence and reprint requests to Vincenzo Eusebi, MD, FRCPath, Sezione di Anatomia, Istologia e Citologia Patologica, Ospedale BeUaria,Via Altura 3, 40139 Bologna, Italy. Copyright © 1999 by W.B. Saunders Company 0046-8177/99/3003-0018510.00/0
356
FIGURE 2. At higher magnifications globoid to elongated elements are clearly visible. (H&E, original magnification x 175).
CASE STUDIES
Myoglobin positivity is intense in the globoid and elongated cells. (ABC, original magnification × 175).
FIGURE 3.
PATHOLOGICAL FINDINGS Gross Features
A hysterectomy and left salpingo-oophorectomy specimen was received. The uterus was enlarged and measured 10 cm between the cornua, l0 cm from fundus to os, and 7 cm along the anterior-posterior diameter. The myometrium showed two intramural nodules with well-circumscribed margins, measuring 5.5 and 3 cm in maximum axis. A submucosal nodule, 1.8 cm across, was also present. The cut surface of all nodules was white and with a whirled appearance.
fascicles of spindle-shaped cells with eosinophilic cytoplasm and blunt ended nuclei. In one small area there were ribbon-like elongated cells with a b u n d a n t eosinophilic cytoplasm and from one to several nuclei located beneath the plasmalemmal membrane (Figs 1, 2). Cytoplasmic crossstriations were also easily observed. Some cells were polygonal and nuclei were located at the periphery of the cell. Nuclei were r o u n d to oval and displayed prominent nucleoli. No mitoses nor necrotic areas were visible. At immunohistochemistry, the ribbon-like and polygonal cells strongly reacted with antiskeletal muscle actin and myoglobin antisera (Figs 3,4) and were weakly positive with antidesmin antiserum. Antivimentin, smooth muscle actin, calponin, and caldesmon anfisera all gave negative results in these cells. In contrast, the spindle-shaped cells, which constituted the major part of the lesion, were reactive with tile latter antisera as well as with anfidesmin antiserum and consistently negative with skeletal muscle acfin and myoglobin anfisera. The endometrium was proliferative, the cervix and left adnexum were within normal limits. At electron microscopy, focal collections of well-differentiated skeletal muscle elements, sometimes having multiple nuclei, were seen. In the cytoplasm, haphazardly arranged rudimentary sarcomeres, Z-discs of varying sizes and shapes as well as dense masses of tangled myofilaments and ribosomes could be observed (Fig 5). A continuous external lamina was a frequent finding. DISCUSSION The lesion described here is predominantly composed of fascicles of spindle-shaped cells with eosinophilic cytoplasm and blunt-ended nuclei, which show no evidence of atypia or mitotic activity and are positive with antivimentin, smooth muscle actin, calponin, caldesmon, and desmin antisera. A second minor component is constituted by ribbon-like and polygonal cells with a b u n d a n t eosinophilic cytoplasm in which cross-striations are easily visible and multiple oval to round nuclei are present. The latter elements also lack
MICROSCOPIC FINDINGS Histological examination of the submucosal and largest intramural nodule showed benign smooth muscle cell proliferation, consistent with the diagnosis of classical leiomyoma. The third nodule appeared more cellular, composed of
FIGURE 4. Antiskeletal muscle actin antiserum (brown) highlights cytoplasmic cross striations, whereas anti smooth muscle actin antiserum (red) decorates smooth muscle cells. (ABC-AP, original magnification x350).
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FIGURE 5. A globoid ceil showing cytoplasmic sarcomeres which show well formed Z-disks (inset). (IEM, original magnification x9,000; inset: original magnification x 15,000).
n u c l e a r atypia as well as mitotic activity. O n i m m u n o h i s t o c h e m istry these cells are positive with a n t i d e s m i n , skeletal m u s c l e acfin, a n d m y o g l o b i n antisera. Ultrastructurally, they show a c o n t i n u o u s e x t e r n a l lamina, r u d i m e n t a r y sarcomeres, a n d Z-discs, w h i c h i n d i c a t e skeletal m u s c l e differentiation. All t h e s e features are c o n s i s t e n t with t h e diagnosis o f l e i o m y o m a with skeletal muscle differentiation. This neop l a s m s h o u l d b e d i f f e r e n t i a t e d f r o m symplastic a n d epithelioid l e i o m y o m a a n d e n d o m e t r i a l stromal n o d u l e (ESN) with skeletal muscle differentiation. Symplastic l e i o m y o m a is characterized by a m o r e m a r k e d n u c l e a r p l e o m o r p h i s m a n d m a y show r n u l f i n u c l e a t e d g i a n t cells6; e p i t h e l i o i d l e i o m y o m a is c o m p o s e d o f r o u n d to p o l y g o n a l cells h a v i n g a b u n d a n t a n d g r a n u l a r cytoplasm with centrally located nucleus, 6 B o t h types of lesion, however, lack cytoplasmic cross-striations; i n addition, i m m u n o r e a c t i v i t y for skeletal m u s c l e actin a n d myoglob i n has n e v e r b e e n r e p o r t e d . 7 ESN with skeletal m u s c l e d i f f e r e n t i a t i o n is a r e c e n t l y d e s c r i b e d entity 8 c o m p o s e d o f e n d o m e t r i a l stromal cells i n t e r m i n g l e d with s m o o t h a n d skeletal muscle c o m p o n e n t s a n d epithelial-like s t r u c t u r e s r e m i n i s c e n t o f sex-cord elements. T h e n e o p l a s m also shows a n a r b o r i z i n g vascular p a t t e r n with vessels similar to t h e spiral arteries o f t h e m i d p r o l i f e r a t i v e e n d o m e t r i u m . This type o f vascularization as well as epithelial-like s t r u c t u r e s are lacking in t h e p r e s e n t lesion. Skeletal muscle d i f f e r e n t i a t i o n h a s b e e n o b s e r v e d w i t h i n a u t e r i n e l e i o m y o m a 1 a n d l e i o m y o s a r c o m a 24 a n d in a u n i q u e case o f r e t r o p e r i t o n e a l leiomyosarcoma. 5 T h e i n t e r p r e t a t i o n o f this p h e n o m e n o n is d e b a t a b l e . W h e n it occurs in a u t e r i n e tumor, it c a n b e c o n s i d e r e d as t h e p h e n o t y p i c e x p r e s s i o n of t h e m u l t i p l e d i f f e r e n t i a t i n g p o t e n tial o f u t e r i n e s m o o t h muscle ceils w h i c h have a Mfillerian origin. Nevertheless, skeletal muscle d i f f e r e n t i a t i o n has also b e e n o b s e r v e d in b e n i g n a n d m a l i g n a n t t u m o u r s w h i c h d i d n o t have e i t h e r m u s c u l a r o r Mfillerian origin, s u c h as sarcomatoid c a r c i n o m a s o f various organs, 91s s e m i n o m a s , 14 m e d u l l o blastomas, 1~-16 liposarcomas, 17 T r i t o n t u m o u r , 18 p l e o m o r p h i c a d e n o m a o f salivary glands,X9 n e u r o e n d o c r i n e t u m o u r s , 2° a n d a variety of n o n g e r m cell tumors. 21 To this list, t h e case o f
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l e i o m y o s a r c o m a o f r e t r o p e r i t o n e u m with r h a b d o m y o b l a s t i c d i f f e r e n t i a t i o n has to b e a d d e d . T h e r e f o r e this p h e n o m e n o n is n o t exclusive to tissues h a v i n g a Mflllerian origin a n d s h o u l d p r o b a b l y b e c o n s i d e r e d as t h e c o n s e q u e n c e of a n a b e r r a n t g e n o m i c d e r e g u l a t i o n w h i c h occurs in neoplastic cells, regardless of t h e i r origin. Skalli a n d G a b b i a n i 22 have s h o w n t h a t s m o o t h muscle cells s h a r e a c o m m o n d e v e l o p i n g pathway with skeletal m u s c l e fibers. T h e r e f o r e it is possible t h a t r h a b d o m y o b l a s t i c e l e m e n t s o b s e r v e d within a s m o o t h m u s c l e cell p r o l i f e r a t i o n , w h e r e v e r localized, are t h e p r o d u c t o f a n o m a l o u s p r o l i f e r a t i o n a l o n g t h e s a m e s t e m line. I r r e s p e c t i v e o f t h e i r o r i g i n , t h e p r e s e n c e o f welld i f f e r e n t i a t e d skeletal muscle e l e m e n t s within a l e i o m y o m a has to b e t a k e n in c o n s i d e r a t i o n in o r d e r to avoid fallacious diagnoses of m a l i g n a n t c o n d i t i o n s .
REFERENCES 1. Martin-ReayDG, Christ ML, LaPata RE: Uterine leiomyoma with skeletal muscle differentiation. AmJ Clin Patho196:344-347, 1991 2. Spirt RH, Koss LG: Myosarcomaof the uterus. Cancer 18:571-588, 1995 3. Hendrickson MR, Kempson RL: Surgical pathology of the uterine corpus, in BenningtonJL (ed): Major Problems in Pathology,Vol. 12. Philadelphia, WB Saunders, p 487, 1980 4. Stout AP: Mesenchyraoma, the mixed tumour of mesenchymal derivafives.Ann Surg 127:278-290, 1948 5. Roncaroli F, Eusebi V: Rhabdomyoblasfic differentiation in a leiomyosarcoma of the retroperitoneum. HuM PATHOL27:310-313, 1996 6. Silverberg SG, Kurman RJ: Atlas of Tumor Pathology. Tumors of the uterine corpus and gestafional trophoblasfic disease. Third series. Fascicle 3. Washington DC, Armed Forced Institute of Pathology. 1991 7. Kurman RJ, Norris HJ: Mesenchymal tumors of the uterus. VI. Epithelioid smooth muscle tumors including leiomyoblastoma and clear cell leiomyoma. A clinical and pathologic analysis of 26 cases, Cancer 37:1853-1856, 1976 8. LloretaJ, PratJ: Endometrial stromal nodule with smooth and skeletal muscle components simulating stromal sarcoma. IntJ Gynecol Pathol 11:293298, 1992 9. Foschini MP, Dina RE, Eusebi V: Sarcomatoid neoplasm of the breast:
BOOK REVIEW Proposed definition for biphasic and monophasic sarcomatoid mammary carcinomas. Sere Diagn Pathol 10:128-136, 1993 10. Goldman RL, Weidner N: Pure squamous cell carcinoma of the larynx with cervical nodal metastases showing rhabdomyosarcomatous differentiation. AmJ Surg Pathol 17:415-421, 1993 11. Humphrey PA, Scroggs M, Roggli VL, et ah Pulmonary carcinoma with a sarcomatoid component. HuM PATHOL19:155-165, 1988 12. Lauwers GY, Scevchuk M, Armenakas N, et al: Carcinosarcoma of the prostate. AmJ Surg Pathol 17:342-349, 1993 13. Snorer DC, Levine DG, RosaiJ: Thymic carcinoma. Am J Surg Pathol 6:451-470, 1982 14. True LD, Otis CN, Delprado V, etal: Spermatocytic seminoma of testis with sarcomatous trasformation. PanJ Surg Pathol 12:1166-1170, 1988 15. Smith TW, DavidsonRI: Medunomyoblastoma.A histologic, histochemica1 and ultrastructural study. Cancer 54:323-332, 1984 16. Rao C, Friedlander ME, Klein E, et al: Medullomyoblastoma in an adult. Cancer 65:157-163, 1990
17. Tallini G, Parham DM, Dias P, et al: Myogenic regulatory protein expression in adult soft tissue sarcomas. AmJ Pathol 144:693-701, 1994 18. Azzopardi GJ, Eusebi V, Tison V, et al: Neurofibroma with rhabdomyomatous differentiation: Benign "Triton" turnout of the vagina. Histopathology 7:561-572, 1983 19. Lam PWA, Chan JKC, Sin W-C: Nasal pleomorphic adenoma with skeletal muscle differentiation: Potential misdiagnosis as rhabdomyosarcoma. HuM PATHOL28:1299-1302, 1997 20. Roncaroli F, Montironi R, Feliciotti F, et al: Sarcomatoid carcinoma of the anorectal junction with neuroendocrine and rhabdomyoblastic features. AmJ Surg Pathol 19:217-223, 1995 21. Woodruff JM, Perino G: Non-germ-cell or teratomatous malignant mmours showing additional rhabdomyoblastic differentiation, with emphasis on the malignant Triton mmour. Sere Diagn Pathol 11:69-81, 1994 22. SkaUiO, Gabbiani G, Bahai F, et ah Intermediate filament proteins and actin isoforms as markers of soft tissue tumor differentiation and origin. II Rhabdomyosarcomas.AmJ Pathol 130:515-531, 1988
BOOK REVIEW Handbook o f Forensic Pathology, V i n c e n t J.M. DiMaio, S u z a n n a E. Dana. Austin, Tx, L a n d e s B i o s c i e n c e / V a d e m e c u m , 1998, 249 pages, $45.00.
i n f o r m a t i o n will find t h e references up-to-date a n d c o m p r e h e n sive. Given r e g i o n a l a n d o t h e r variations in forensic practice, individual r e a d e r s will n o d o u b t find areas o f p r o c e d u r a l a n d t h e o r e t i c a l d i s a g r e e m e n t with the a u t h o r s , for e x a m p l e in t h e i r practice o f m a r k i n g bullets, w h i c h is by n o m e a n s universal. This is n o t a weakness o f t h e text, w h i c h by necessity is b a s e d o n t h e e x p e r i e n c e o f t h e c o a u t h o r s . T h e y are careful to n o t e in t h e Preface t h a t "variations will o c c u r " f r o m t h e m o s t c o m m o n findings. This b o o k is s u p e r i o r a m o n g g e n e r a l forensic p a t h o l o g y texts i n its e m p h a s i s o n p r o c e d u r e s , w h i c h equals t h a t in forensic investigation h a n d b o o k s written for m e d i c a l investigation a n d law e n f o r c e m e n t audiences. T h e c h a p t e r s o n Physical E v i d e n c e a n d I d e n t i f i c a t i o n o f R e m a i n s are particularly welcome. T h e greatest s t r e n g t h o f this work is its u n c o m p r o m i s i n g a d h e r e n c e to scientific p r i n c i p l e s u n d e r l y i n g m o d e r n forensic p a t h o l o g y practice. It will p r o v e m o s t h e l p f u l to r e s i d e n t s a n d fellows in t r a i n i n g at m e d i c a l e x a m i n e r s ' offices a n d to m e d i c a l s t u d e n t s d e s i r i n g e x p o s u r e to t h e growing field of forensic pathology. Because o f its concise f o r m a t , d e p t h , a n d well-chosen references, it will also b e o f use to t h e p r a c t i s i n g m e d i c a l e x a m i n e r in t h e investigation o f i n f r e q u e n t l y e n c o u n t e r e d deaths, such as electrocutions.-CAROLYN H. REVERCOMB, MD, Assistant Medieal Examine,; Medical Examiner's Office, City of
T h e stated p u r p o s e o f this b o o k is to p r o v i d e a t r a i n i n g m a n u a l in forensic p a t h o l o g y for m e d i c a l students, residents, a n d fellows. T h e e m p h a s i s is o n basic principles o f forensic pathology, i n c l u d i n g t h e basis f o r forensic autopsy p r o c e d u r e , a n d o n c o m m o n f i n d i n g s in t h e variety o f d e a t h s e n c o u n t e r e d by m e d i c a l e x a m i n e r s . T h e spiral b o u n d f o r m a t , small type, a n d r e l i a n c e o n text over b l a c k a n d white illustrations recall t h e W a s h i n g t o n M a n u a l series. W h e r e p h o t o g r a p h s a n d d i a g r a m s d o a p p e a r they are effective. T h e r e are 20 c h a p t e r s w h i c h r a n g e i n l e n g t h f r o m 2 pages ( I n t r a o p e r a t i v e D e a t h s ) to 30 pages (Natural Disease, B l u n t Force Injury, G u n s h o t W o u n d s ) . Because t h e divisions are o u t l i n e d o n t h e b a c k cover, a n i n f o r m e d r e a d e r c a n find m o s t i n f o r m a t i o n quickly w i t h o u t t h e aid o f t h e seven-page index. T h e a u t h o r s s u c c e e d i n d e s c r i b i n g m a n y of t h e m o r e c o m p l e x areas of forensic pathology, i n c l u d i n g asphyxia, t h e r m a l injuries, a n d b l u n t t r a u m a , with u n u s u a l clarity a n d d e p t h . T h e r a n g e o f m a t e r i a l c o v e r e d is ambitious, a n d it is t h e r e f o r e n o t s u r p r i s i n g t h a t t h e e l a b o r a t i o n o f s o m e specialized subjects, such as i n t e r p r e t a t i o n o f findings in forensic toxicology, is relatively thin. However, those d e s i r i n g f u r t h e r
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the p a t h o g e n e s i s o f m y o f i b r o b l a s t o m a . T h e i r o b s e r v a t i o n s a p p e a r to p r o v i d e a n i m p o r t a n t piece o f t h e puzzle, b u t t h e cellular substrate involved in t h e f o r m a t i o n o f myofibroblast o m a was is a d d r e s s e d only historically. We are s t u d y i n g two subsets o f strornal d e n d r i t i c cells: u n c o m m i t t e d fibroblasts t h a t express t h e p r o g e n i t o r cell a n t i g e n CD34 a n d histiocytes t h a t express c o a g u l a t i o n factor XIIIa. T h e s e u b i q u i t o u s cells a p p e a r to i n t e r a c t d u r i n g stromal m o r p h o g e n e s i s a n d in t h e
To the Editon'---We r e a d with i n t e r e s t t h e article by Drs. M o r g a n a n d P i t h a 1 r e p o r t i n g e x p r e s s i o n o f a n d r o g e n receptors in five m a m m a r y m y o f i b r o b l a s t o m a s in b o t h sexes. T h e y also s t u d i e d o t h e r s p i n d l e cell t u m o r s t h a t d i d n o t express a n d r o g e n receptor. T h e a u t h o r s state t h a t despite d e t a i l e d k n o w l e d g e o f c l i n i c o p a t h o l o g i c features, little is k n o w n a b o u t
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