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Subsequently Occurring Leiomyosarcoma and Desmoid Tumor of the Right Thigh
Path. Res. Pract. 188,360-364 (1992)
Subsequently Occurring Leiomyosarcoma and Desmoid Tumor of the Right Thigh S. Biesterfeld, M. Kleinl, J. Dose, K. Bohndorf1 and L. Füzesi Institute of Pathology and lClinic of Radiological Diagnostics, Technical University, Aachen, FRG
Summary We present the case of a 44-year-old patient with a primary leiomyosarcoma of the right upper thigh, who developed a second mesenchymallesion at the same thigh, diagnosed as an extra-abdominal desmoid tumor, same months after surgical treatment of his leiomyosarcoma. Clinically, histomorphologically, DNA cytometrically, immunohistochemically and radiologically the different histogenetic origin of the two lesions could be proven. The patient died 17 months after his first tumor diagnosis of lung metastases of his leiomyosarcoma.
Introducrion The occurrence of two soft tissue tumors of the same extremity during some months only makes it necessary to decide whether the second lesion is a recurrence of the former tumor or if a second primary tumor has to be diagnosed, the latter alternative being extremely rare 10 • We observed a case of primary leiomyosarcoma of the right thigh, originating from the profound femoral vein, followed months later by a desmoid tumor located supraand retropatellary, and present the different clinical, radiological, histopathological, immunohistochemical and DNA cytometric investigations, which were used to arrive at the final diagnoses.
Case Report First Mesenchymal Lesion
A 44-year-old man was admitted with an almost painless tumor of the right thigh, rapidly enlarging during four months. Clinically a malignant mesenchymal process was presumed. Ultrasound showed a tumor 12.5 to 9 cm in diameter, which was sharply delineated from the surrounding tissue. 0344-0338/92/0188-0360$3.50/0
The lesion was of low echo intensity in the peripheral and inhomogenous in the central parts. These findings were confirmed by computed tomography. The tumor was hypodense (40 HU) compared with the quadriceps muscle (65 HU) and showed marginal enhancement after bolus injection of 75 ml non-ionic contrast medium. There was no enhancement in the central parts of the tumor, indicating necrotic areas. The examination provided no evidence of infiltration of the surrounding soft-tissue or bony destruction. MRI demonstrated a lobulated, well-defined mass with lateral edema. The tumor showed slightly increased signal intensities in the Trweighted sequence and markedly increased signal intensities in the T 2-weighted images (Fig. 1). Focal hyperintense areas occurred in the ventral parts indicating intralesional hemorrhages. An intraarterial digital subtractive angiography (DSA) revealed a pathological arterial vascular pattern concerning the profound femoral artery. The results of these investigations were interpreted as consistent with sarcoma. After complete resection of the anterior compartment of the right thigh a 12 x 8 x 7 cm sized yellowish tumor with centrally located necrotic and hemorrhagic areas, supplied by the arteria femoralis profunda, was investigated microscopically (Fig. 2). It showed elongated cells with spindle© 1992 by Gustav Fischer Verlag, Stuttgart
Leiomyosarcoma and Desmoid Tumor of the Right Thigh . 361
Fig. 2. High grade leiomyosarcoma with elongated cells with spindle-shaped hyperchromatic nuclei revealing coarse chromatin. Increased mitotic activity. H & E, 70 x. nuclei (".) 40
Fig.1. Coronally orientated, Trweighted magnetic resonance image (TR = 1800 ms, TE = 90 ms) of a high grade leiomyosarcoma of the proximal right thigh, originated from the vena femoralis profunda. Hyperintense signal pattern in comparison to the surrounding muscles.
36 30 26 20 l
shaped hypercllfomatic nuclei with coarse chromatin and deeply acidophilic cytoplasm. Clear intracytoplasmatic vacuoles could be seen perinuclearly. Mitotic figures were numerous. Furthermore so me polynuclear giant cells were observed. Immunohistochemically the tumor cells reacted positive against desmin and showed no reaction against vimentin, myoglobin, actin and myosin. The final diagnosis was a moderately differentiated to undifferentiated leiomyosarcoma of the profound femoral vein. A DNA ploidy analysis of 200 tumor nuclei was performed at random on Feulgen-stained monolayer smears from a cell separation on paraffin-embedded, formalin fixed material using a TV-image analysis system TAS-plus (Leitz, FRG) I, 15 . The DNA ploidy histogram revealed a highly aneuploid DNA distribution pattern with two aneuploid peaks at 2.75c and 8.75c and nuclei with DNA contents up to 15.5 c resulting in a DNA-Malignancy Grade4 of 2.74 on the scale ranging from 0 to 3 (Fig.3). Second Mesenchymal Lesion
Four months later the patient presented another tumorous lesion of the same thigh located supra- and retropatellary, clinically interpreted as a hematoma or recurrence of the leiomyosarcoma. Using magnetic resonance imaging performing T 1- and T 2-weighted sequences in axial and coronal orientation a 4 x 2.5 cm sized tumor with a different signal intensity
10
j
10
6 0
2
4
6
6
10
12
ploldy (01 16
Fig. 3. Highly aneuploid DNA frequency histogram (black) of a high grade leiomyosarcoma witb rwo aneuploid peaks at 2.75 c and 8.75c and a DNA Malignancy Grade of 2.74; DNA frequency histogram of a low grade desmoid tumor with an aneuploid peak at 2.75c and a DNA Malignancy Grade of 0.30 (hatched).
pattern compared to the ·leiomyosarcoma, being almost identical to that of the surrounding muscles, was identified (Fig. 4). This lesion was supposed to grow infiltratively because of its ill-defined margin exactly matching with the later pathological findings. A conventional intraarterial angiography revealed a pathological arterial vascular pattern concerning the superficial femoral artery. Grossly this second lesion was of a mostly wellcircunlscribed growth pattern. Microscopically (Fig. 5) it consisted of wide, hyalinized collagen bundles with focally proliferating fibroblasts with oval nuclei and eosinophilic cytoplasm. Mitotic activity was sparse. An immunohistochemical analysis proved a positive reaction against vimen-
362 . S. Biesterfeld et al.
tissue, revealed an aneuploid DNA distribution pattern with a peak at 2.75c. The highest DNA single value was found at 5.25 c. The DNA Malignancy Grade4 was calculated to be 0.30 on the scale ranging from 0 to 3 reflecting a low malignant potential (Fig. 3). Clinical Course
Fig.4. Coronally orientated, Trweighted magnetic resonance image (TR = 2200 ms, TE = 90 ms) of a desmoid tumor of the distal right thigh, originated from the vena femoralis superficialis. Mostly isointense signal pattern in comparison to the surrounding muscles.
The clinical course of the patient depended on the clinical behaviour of his leiomyosarcoma. At the date of the leiomyosarcoma resection there was no histopathological evidence for inguinal lymph node infiltration; chest X-ray, abdominal sonography and bone scintigraphy were negative. During the follow-up period, when the respective investigations were repeatedly performed, there was never any suspicion for metastases in inguinal, paraaortal or mediastinal lymph nodes, liver or sceletal system. However, the patient suffered from lung metastases. Four mondls later, when the desmoid tumor was surgically treated, a solitary lung meta stasis of the medial segment of the right middle lobe sized 2 x 2 cm was seen radiologically, most likely originated from the leiomyosarcoma. This finding was verified by two computed tomographies (CT) of the lung; a fine needle aspiration biopsy in order to clarify the histogenetic origin of the metastasis was refused by the patient. Another four mondls later, a third lung CT revealed multiple metastases over both lungs. During the next mondls, although six cycles of a chemotherapy scheme with each Farmorubicin (90 mg, 1st day) and Holoxan (3 x 1000 mg, 2nd to 6th day) were given, an increasing tendency of most of the lung metastases and the occurrence of new ones were described. Finally a left-sided malignant pleural effusion with evidence of leiomyosarcoma cells was diagnosed cytopathologically, and the patient died of respiratory insufficiency, 17 months after the surgical resection of his leiomyosarcoma.
Discussion
Fig. 5. Desmoid tumor with hyalinized collagen bundles and focally proliferating fibroblasts revealing oval nuclei with prominent nucleoles and eosinophilic cytoplasm. H & E, 70x.
tin and a negative one against desmin, myoglobin, actin and myosin. The tumor was finally diagnosed to be an extraabdominal desmoid tumor. A DNA ploidy analysis, performed under the same conditions as described above for the leiomyosarcoma
The occurrence of two tumorous lesions in the soft tissue of the same extremity during the period of only some months mainly creates the problem if they have to be interpreted as primary and recurrent tumor of the same histogenetic origin or as two independent primaries of different histogenetic classification. Firsdy, a large leiomyosarcoma was diagnosed, originating from the vena femoralis profunda. These rare vascular leiomyosarcomas are most common in large veins such as the vena cava, foUowed by pulmonary artery and saphenous or femoral veins lO , 12. In general, the patient's prognosis mainly depends on two aspects; i.e. their vasoconstrictive effect on the circulation of the dependent anatomical regions and the risk for the occurrence of distant metastases 3 • For a tumor of the profound femoral vein only the latter is of importance, as a presumably occurring constriction of the respective vein will neither influence the
Leiomyosarcoma and Desmoid Tumor of the Right Thigh . 363
teehnieal operability of the lesion nor will it have the eonsequenee of a life threatening disturbanee of eireulation. Although the therapy of ehoiee, the eomplete tumor reseetion, eould be sueeessfu11y performed and there was no evidel1ee of regional or distant metastases at the time of surgery, the risk for metastases had to be looked upon as high beeause of the tumor's large size and its poor histopathologieal differentiation. Additiona11y, there is consensus in the literature that highly aneuploid DNA distribution patterns as analyzed in this tumor, refleet shortened survival probabilities and an inereased rate of both loeal reeurrenee and distant metastasis 2, 5, 6,11,16. Therefore, in eonclusion, control of the loeation of surgery, sonography of regionallymph nodes and liver and X-ray of the ehest are neeessary using short intervals in order to sereen for lymph node-, liver- or lung metastases. The lesion reseeted four months later was classified as an extraabdominal desmoid tumor; a reeurrenee of the leiomyosareoma was made unlikely by the eomparison of magnetie resonanee imaging, histologie appearanee, the results of immunohistoehemical investigations and the DNA ploidy pattern of the two lesions, which were a11 different. Furthermore, recurrence dista11y sited to the primary tumor would be at least unusuaL Diagnostic imaging of neoplastic processes is limited on information concerning extension (size, infiltration and destruction) and proposed dignity7,17. This is mainly due to the limitation of most imaging methods to only one parameter (roentgen-density, echo-impedance) whieh provi des not enough tissue contrast l4 . Magnetic resonance imaging, however, is based on three main parameters (T 1-, T 2-relaxation, proton density) resulting in a multitude of signal patterns for the different tissue types 18 . In the presented case, this capacity permitted the differentiation of the secondary tumor from local recurrence or metastasis, which were clinica11y much more likely. Immunohistochemically the positive reaction of the leiomyosarcoma tissue with desmin is considered to be typical for skeletal or smooth muscle tumors lO and is therefore consistent with the histopathologieal diagnosis. The negativity against myoglobin as a marker for skeletal muscle cells supports the origin of the diagnosed muscle tumor from smooth muscle cells. The desmoid tumor reaeted positive against vimentin as a marker for mesenchymal fibrous tumors; a muscle tumor was made unlikely by its negativity against desmin and the other different markers for muscle cells. Extraabdominal desmoid tumors are considered as low-grade fibrosarcomas with a high incidence of loeal reeurrence from 25 % to 65 % 10,12. The therapy of ehoice is the complete resection of this locally infiltrative lesion including the excision of a wide margin of macroscopically uninvolved tissue 8,9, 13, 19 in order to avoid local recurrence. The low malignant potential of extraabdominal desmoid tumors in general could be verified in our case by a DNA cytometric analysis of the tumor cell population: The detection of an aneuploid stemline at 2.75 c is a hard marker for the malignant character of the lesion 2 ; the DNA
Malignancy Grade of 0.30 on a scale ranging from 0 to 3 is consistent with a low malignant potential and a DNA cytometrically supported low risk for metastases. Consistently the clinical course of the patient, whose ca se we report because of the extremely rare almost coineidental oceurrence of t\VO histogenetica11y independent mesenchymal malignancies within four months on the same extremity, depended on the occurrence of lung metastases of the high grade leiomyosarcoma. References 1 Auffermann W, Repges R, Böcking A (1984) Rapid diagnostic DNA cytometry with an automatie microscope and a TV image-analysis system. Analyt Quant Cytol6: 178-188 2 Barlogie B, Drewinko B, Schumann], Göhde W, Dosik G, Latreille ], Johnston DA, Freireich EJ (1980) Cellular DNA conte nt as a marker of neoplasia in man. Am J Med 69: 195-203 3 Berlin 0, Stener B, Kindbiom L, Angervall L (1984) Leiomyosarcomas of venous origin in the extremities. A correlated clinical, roentgenologic and morphologie study with diagnostic and surgical implications. Cancer 54: 2147-2159 4 Böcking A, Auffermann W (1986) Algorithm for a DNAcytophotometric diagnosis and grading of malignancy. Analyt Quant Cytol Histol 8: 383 5 Böcking A, Chatelain R (1989) Diagnostic and prognostic value of DNA cytometry in gynecologic cytology. Analyt Quant Cytol Histol 11: 177-186 6 Böhm N, Sandritter W (1975) DNA in human tumors: A cytophotometric study. Curr Top Pathol 60: 151-219 7 BohndorfK, Reiser M, Friedmann G, Ghusscn F, Holzmüller W, Stein brich W (1987) Wert der Kernspintomographie vor chirurgischer Therapie und Radiatio peripherer Weichteiltumoren. Fortschr Röntgenstr 146: 130-136 8 Dahn I, Jonsson N, Lundh G (1963) Desmoid tumors. A se ries of 33 cases. Acta Chir Scand 126: 305-313 9 Das Gupta TK, Brasfield RD, O'Hara J (1967) Extraabdominal desmoids. A clinicopathological study. Ann Surg 170: 109-121 10 Enzinger FM, Weiss SW (1988) Soft Tissue Tumors. 2nd cd., CV Mosby, St. Louis 11 Friedlander ML, Hedley DW, Taylor IW (1984) Clinical and biological significance of aneuploidy in human tumours. ] Clin Pathol37: 961-974 12 Hajdu SI (1979) Pathology of Soft Tissue TUmors. Lea & Febiger, Philadelphia 13 Hunt RTN, Morgan HC, Ackerman LV (1960) Principles in the management of extraabdominal desmoids. Cancer 13: 825-836 14 Reiser M, Wiesmann W, Erlemann A, Härle A, Bohndorf K, Wuismann P, Kunze V, Peters PE (1988) Computertomographie und magnetische Resonanztomographie bei Weichteiltumoren. Orthopäde 17: 134-142 15 Sanchez L, Regh M, Biesterfeld S, Chatelain R, Böcking A (1990) Performance of a TV image analysis system as microdensitometer. Analyt Quant Cytol Histol 12: 279-284 16 Seckinger D, Sugarbaker E, Frankfurt 0 (1989) DNA conte nt in human cancer. Arch Pathol Lab Med 113:
619~626
17 Tehranzadeh J, Mnaymneh W, Ghavam C, Morillo G, Murphy BJ (1989) Comparison of CT and MR imaging in musculoskeletal neoplasms. ] Comp Assist Tomogr 13: 466-472
364 . ]. Sugar !8 Vanel D, Lacombe M], Couanet D, Kalifa C, Spielmann M, Genin] (1987) Musculosceletal tumors: Follow-up with MR imaging after treatment with surgery and radiation. Radiology 164: 243-245
!9 Weinstein EC, Payne WS, Soule EH (1963) Surgical treatment of desmoid tumor of the ehest wall. ] Thorae Surg 46: 242-251
Reeeived ]uly 17,1990· Accepted August 15, 1991
Key words: Soft tissue tumor - Leiomyosarcoma - Desmoid tumor - DNA cytometry - MR tomography Dr. med. L. Füzesi, Institut für Pathologie der RWTH Aachen, Pauwelsstr. 30, D-5100 Aachen, FRG
Letters to the Case J. Sugar Budapest, Hungary
It is not a rarity at all that two different tumours develop simultaneously or subsequently within the same region. From a diagnostic point of view it is more fortunate if the two tumours exhibit essential differences in histogenesis and histological structure. In this paper, however, the authors faced a knotty problem because: 1) Both belonged to the same group, i.e. they were of mesenchymal soft tissue origin, 2) The relatively less malignant desmoid tumour (DT) developed in the region of the highly malignant and metastasizing leiomyosarcoma (LS), soon after its surgical removal. The authors claim that these tumours developed subsequently and independently of each other. They think the inequality of the two tumours has to be verified by: 1) the different histological patterns, 2) the different immunohistochemical reactions and, 3) the different DNA cytometric values. In my letter to the case I try to outline - as usual in this journal- 1) wh at sort of more decisive arguments for the discrimination of the two tumours could been obtained and 2) to state whether the data provided by the authors are sufficient to prove their diagnoses. Based on the enclosed histologic picture the authors are right to think that in all probability the primary lesion corresponds to LS. As concerns its immunohistochemical behaviour it seems at present that while some LS-s are desmin negative, the presence of this marker excludes the diagnosis of fibrosarcoma or malignant fibrous histiocytoma (MFH) or myofibrosarcoma. It may happen that not all LS-s are positive for desmin. Miettinen lO observed
desmin positivity in 86-91 % of his LS cases. This value was, however, significantly lower in the study of Leader et al. 8 . It is fairly known that the intermediate filaments may contain identical epitopes that frequently lead to the coexpression of markers of the epithelium, muscles and connective tissue4 • Vimentin reacts not only with connective tissue but also with smooth muscle cells. Sometimes MFH mayaiso be positive for desmin. Positivity in these cases is probably attributable to myofibroblasts 7- 9 • I have mentioned these facts because desmin negativity and vimentin positivity of the second tumour (DT) do not exclude unequivocally the smooth muscle origin. Smooth muscle per se and most of the tumours arising from it are positive for anti-smooth muscle myosin!! and also for muscle actins. Therefore, desmin is not an absolute marker. In fact, muscle actins are at least as specific as desmin 9 • Several synonyms are in use for DT, for instance, desmoid fibromatosis, aggressive fibromatosis, infiltrative fibromatosis 6 . All these terms containing the word "fibromatosis" refer, in fact, to the richness of the intercellular matrix and ground substance in fibers and to the poor cellularity of the tumour. Naturally, DT-s mayaiso have some parts showing rich cellularity and bizarre neoplastic fibroblasts with 2-3 nuclei 6 • The enclosed figure can be accepted to demonstrate such a portion of DT. . DT-s are recurring and aggressive but not metastasizing fibroses. Consequently, they can be regarded as tumours of intermediate malignancy. I agree with the authors in that DNA morpho- and cytometry are helpful in judging malignancy. I was searching for some publications on the
Subsequently Occurring Leiomyosarcoma and Desmoid Tumor of the Right Thigh S. Biesterfeld, M. Kleinl, J. Dose, K. Bohndorf1 and L. Füzesi Institute of Pathology and lClinic of Radiological Diagnostics, Technical University, Aachen, FRG
Summary We present the case of a 44-year-old patient with a primary leiomyosarcoma of the right upper thigh, who developed a second mesenchymallesion at the same thigh, diagnosed as an extra-abdominal desmoid tumor, same months after surgical treatment of his leiomyosarcoma. Clinically, histomorphologically, DNA cytometrically, immunohistochemically and radiologically the different histogenetic origin of the two lesions could be proven. The patient died 17 months after his first tumor diagnosis of lung metastases of his leiomyosarcoma.
Introducrion The occurrence of two soft tissue tumors of the same extremity during some months only makes it necessary to decide whether the second lesion is a recurrence of the former tumor or if a second primary tumor has to be diagnosed, the latter alternative being extremely rare 10 • We observed a case of primary leiomyosarcoma of the right thigh, originating from the profound femoral vein, followed months later by a desmoid tumor located supraand retropatellary, and present the different clinical, radiological, histopathological, immunohistochemical and DNA cytometric investigations, which were used to arrive at the final diagnoses.
Case Report First Mesenchymal Lesion
A 44-year-old man was admitted with an almost painless tumor of the right thigh, rapidly enlarging during four months. Clinically a malignant mesenchymal process was presumed. Ultrasound showed a tumor 12.5 to 9 cm in diameter, which was sharply delineated from the surrounding tissue. 0344-0338/92/0188-0360$3.50/0
The lesion was of low echo intensity in the peripheral and inhomogenous in the central parts. These findings were confirmed by computed tomography. The tumor was hypodense (40 HU) compared with the quadriceps muscle (65 HU) and showed marginal enhancement after bolus injection of 75 ml non-ionic contrast medium. There was no enhancement in the central parts of the tumor, indicating necrotic areas. The examination provided no evidence of infiltration of the surrounding soft-tissue or bony destruction. MRI demonstrated a lobulated, well-defined mass with lateral edema. The tumor showed slightly increased signal intensities in the Trweighted sequence and markedly increased signal intensities in the T 2-weighted images (Fig. 1). Focal hyperintense areas occurred in the ventral parts indicating intralesional hemorrhages. An intraarterial digital subtractive angiography (DSA) revealed a pathological arterial vascular pattern concerning the profound femoral artery. The results of these investigations were interpreted as consistent with sarcoma. After complete resection of the anterior compartment of the right thigh a 12 x 8 x 7 cm sized yellowish tumor with centrally located necrotic and hemorrhagic areas, supplied by the arteria femoralis profunda, was investigated microscopically (Fig. 2). It showed elongated cells with spindle© 1992 by Gustav Fischer Verlag, Stuttgart
Leiomyosarcoma and Desmoid Tumor of the Right Thigh . 361
Fig. 2. High grade leiomyosarcoma with elongated cells with spindle-shaped hyperchromatic nuclei revealing coarse chromatin. Increased mitotic activity. H & E, 70 x. nuclei (".) 40
Fig.1. Coronally orientated, Trweighted magnetic resonance image (TR = 1800 ms, TE = 90 ms) of a high grade leiomyosarcoma of the proximal right thigh, originated from the vena femoralis profunda. Hyperintense signal pattern in comparison to the surrounding muscles.
36 30 26 20 l
shaped hypercllfomatic nuclei with coarse chromatin and deeply acidophilic cytoplasm. Clear intracytoplasmatic vacuoles could be seen perinuclearly. Mitotic figures were numerous. Furthermore so me polynuclear giant cells were observed. Immunohistochemically the tumor cells reacted positive against desmin and showed no reaction against vimentin, myoglobin, actin and myosin. The final diagnosis was a moderately differentiated to undifferentiated leiomyosarcoma of the profound femoral vein. A DNA ploidy analysis of 200 tumor nuclei was performed at random on Feulgen-stained monolayer smears from a cell separation on paraffin-embedded, formalin fixed material using a TV-image analysis system TAS-plus (Leitz, FRG) I, 15 . The DNA ploidy histogram revealed a highly aneuploid DNA distribution pattern with two aneuploid peaks at 2.75c and 8.75c and nuclei with DNA contents up to 15.5 c resulting in a DNA-Malignancy Grade4 of 2.74 on the scale ranging from 0 to 3 (Fig.3). Second Mesenchymal Lesion
Four months later the patient presented another tumorous lesion of the same thigh located supra- and retropatellary, clinically interpreted as a hematoma or recurrence of the leiomyosarcoma. Using magnetic resonance imaging performing T 1- and T 2-weighted sequences in axial and coronal orientation a 4 x 2.5 cm sized tumor with a different signal intensity
10
j
10
6 0
2
4
6
6
10
12
ploldy (01 16
Fig. 3. Highly aneuploid DNA frequency histogram (black) of a high grade leiomyosarcoma witb rwo aneuploid peaks at 2.75 c and 8.75c and a DNA Malignancy Grade of 2.74; DNA frequency histogram of a low grade desmoid tumor with an aneuploid peak at 2.75c and a DNA Malignancy Grade of 0.30 (hatched).
pattern compared to the ·leiomyosarcoma, being almost identical to that of the surrounding muscles, was identified (Fig. 4). This lesion was supposed to grow infiltratively because of its ill-defined margin exactly matching with the later pathological findings. A conventional intraarterial angiography revealed a pathological arterial vascular pattern concerning the superficial femoral artery. Grossly this second lesion was of a mostly wellcircunlscribed growth pattern. Microscopically (Fig. 5) it consisted of wide, hyalinized collagen bundles with focally proliferating fibroblasts with oval nuclei and eosinophilic cytoplasm. Mitotic activity was sparse. An immunohistochemical analysis proved a positive reaction against vimen-
362 . S. Biesterfeld et al.
tissue, revealed an aneuploid DNA distribution pattern with a peak at 2.75c. The highest DNA single value was found at 5.25 c. The DNA Malignancy Grade4 was calculated to be 0.30 on the scale ranging from 0 to 3 reflecting a low malignant potential (Fig. 3). Clinical Course
Fig.4. Coronally orientated, Trweighted magnetic resonance image (TR = 2200 ms, TE = 90 ms) of a desmoid tumor of the distal right thigh, originated from the vena femoralis superficialis. Mostly isointense signal pattern in comparison to the surrounding muscles.
The clinical course of the patient depended on the clinical behaviour of his leiomyosarcoma. At the date of the leiomyosarcoma resection there was no histopathological evidence for inguinal lymph node infiltration; chest X-ray, abdominal sonography and bone scintigraphy were negative. During the follow-up period, when the respective investigations were repeatedly performed, there was never any suspicion for metastases in inguinal, paraaortal or mediastinal lymph nodes, liver or sceletal system. However, the patient suffered from lung metastases. Four mondls later, when the desmoid tumor was surgically treated, a solitary lung meta stasis of the medial segment of the right middle lobe sized 2 x 2 cm was seen radiologically, most likely originated from the leiomyosarcoma. This finding was verified by two computed tomographies (CT) of the lung; a fine needle aspiration biopsy in order to clarify the histogenetic origin of the metastasis was refused by the patient. Another four mondls later, a third lung CT revealed multiple metastases over both lungs. During the next mondls, although six cycles of a chemotherapy scheme with each Farmorubicin (90 mg, 1st day) and Holoxan (3 x 1000 mg, 2nd to 6th day) were given, an increasing tendency of most of the lung metastases and the occurrence of new ones were described. Finally a left-sided malignant pleural effusion with evidence of leiomyosarcoma cells was diagnosed cytopathologically, and the patient died of respiratory insufficiency, 17 months after the surgical resection of his leiomyosarcoma.
Discussion
Fig. 5. Desmoid tumor with hyalinized collagen bundles and focally proliferating fibroblasts revealing oval nuclei with prominent nucleoles and eosinophilic cytoplasm. H & E, 70x.
tin and a negative one against desmin, myoglobin, actin and myosin. The tumor was finally diagnosed to be an extraabdominal desmoid tumor. A DNA ploidy analysis, performed under the same conditions as described above for the leiomyosarcoma
The occurrence of two tumorous lesions in the soft tissue of the same extremity during the period of only some months mainly creates the problem if they have to be interpreted as primary and recurrent tumor of the same histogenetic origin or as two independent primaries of different histogenetic classification. Firsdy, a large leiomyosarcoma was diagnosed, originating from the vena femoralis profunda. These rare vascular leiomyosarcomas are most common in large veins such as the vena cava, foUowed by pulmonary artery and saphenous or femoral veins lO , 12. In general, the patient's prognosis mainly depends on two aspects; i.e. their vasoconstrictive effect on the circulation of the dependent anatomical regions and the risk for the occurrence of distant metastases 3 • For a tumor of the profound femoral vein only the latter is of importance, as a presumably occurring constriction of the respective vein will neither influence the
Leiomyosarcoma and Desmoid Tumor of the Right Thigh . 363
teehnieal operability of the lesion nor will it have the eonsequenee of a life threatening disturbanee of eireulation. Although the therapy of ehoiee, the eomplete tumor reseetion, eould be sueeessfu11y performed and there was no evidel1ee of regional or distant metastases at the time of surgery, the risk for metastases had to be looked upon as high beeause of the tumor's large size and its poor histopathologieal differentiation. Additiona11y, there is consensus in the literature that highly aneuploid DNA distribution patterns as analyzed in this tumor, refleet shortened survival probabilities and an inereased rate of both loeal reeurrenee and distant metastasis 2, 5, 6,11,16. Therefore, in eonclusion, control of the loeation of surgery, sonography of regionallymph nodes and liver and X-ray of the ehest are neeessary using short intervals in order to sereen for lymph node-, liver- or lung metastases. The lesion reseeted four months later was classified as an extraabdominal desmoid tumor; a reeurrenee of the leiomyosareoma was made unlikely by the eomparison of magnetie resonanee imaging, histologie appearanee, the results of immunohistoehemical investigations and the DNA ploidy pattern of the two lesions, which were a11 different. Furthermore, recurrence dista11y sited to the primary tumor would be at least unusuaL Diagnostic imaging of neoplastic processes is limited on information concerning extension (size, infiltration and destruction) and proposed dignity7,17. This is mainly due to the limitation of most imaging methods to only one parameter (roentgen-density, echo-impedance) whieh provi des not enough tissue contrast l4 . Magnetic resonance imaging, however, is based on three main parameters (T 1-, T 2-relaxation, proton density) resulting in a multitude of signal patterns for the different tissue types 18 . In the presented case, this capacity permitted the differentiation of the secondary tumor from local recurrence or metastasis, which were clinica11y much more likely. Immunohistochemically the positive reaction of the leiomyosarcoma tissue with desmin is considered to be typical for skeletal or smooth muscle tumors lO and is therefore consistent with the histopathologieal diagnosis. The negativity against myoglobin as a marker for skeletal muscle cells supports the origin of the diagnosed muscle tumor from smooth muscle cells. The desmoid tumor reaeted positive against vimentin as a marker for mesenchymal fibrous tumors; a muscle tumor was made unlikely by its negativity against desmin and the other different markers for muscle cells. Extraabdominal desmoid tumors are considered as low-grade fibrosarcomas with a high incidence of loeal reeurrence from 25 % to 65 % 10,12. The therapy of ehoice is the complete resection of this locally infiltrative lesion including the excision of a wide margin of macroscopically uninvolved tissue 8,9, 13, 19 in order to avoid local recurrence. The low malignant potential of extraabdominal desmoid tumors in general could be verified in our case by a DNA cytometric analysis of the tumor cell population: The detection of an aneuploid stemline at 2.75 c is a hard marker for the malignant character of the lesion 2 ; the DNA
Malignancy Grade of 0.30 on a scale ranging from 0 to 3 is consistent with a low malignant potential and a DNA cytometrically supported low risk for metastases. Consistently the clinical course of the patient, whose ca se we report because of the extremely rare almost coineidental oceurrence of t\VO histogenetica11y independent mesenchymal malignancies within four months on the same extremity, depended on the occurrence of lung metastases of the high grade leiomyosarcoma. References 1 Auffermann W, Repges R, Böcking A (1984) Rapid diagnostic DNA cytometry with an automatie microscope and a TV image-analysis system. Analyt Quant Cytol6: 178-188 2 Barlogie B, Drewinko B, Schumann], Göhde W, Dosik G, Latreille ], Johnston DA, Freireich EJ (1980) Cellular DNA conte nt as a marker of neoplasia in man. Am J Med 69: 195-203 3 Berlin 0, Stener B, Kindbiom L, Angervall L (1984) Leiomyosarcomas of venous origin in the extremities. A correlated clinical, roentgenologic and morphologie study with diagnostic and surgical implications. Cancer 54: 2147-2159 4 Böcking A, Auffermann W (1986) Algorithm for a DNAcytophotometric diagnosis and grading of malignancy. Analyt Quant Cytol Histol 8: 383 5 Böcking A, Chatelain R (1989) Diagnostic and prognostic value of DNA cytometry in gynecologic cytology. Analyt Quant Cytol Histol 11: 177-186 6 Böhm N, Sandritter W (1975) DNA in human tumors: A cytophotometric study. Curr Top Pathol 60: 151-219 7 BohndorfK, Reiser M, Friedmann G, Ghusscn F, Holzmüller W, Stein brich W (1987) Wert der Kernspintomographie vor chirurgischer Therapie und Radiatio peripherer Weichteiltumoren. Fortschr Röntgenstr 146: 130-136 8 Dahn I, Jonsson N, Lundh G (1963) Desmoid tumors. A se ries of 33 cases. Acta Chir Scand 126: 305-313 9 Das Gupta TK, Brasfield RD, O'Hara J (1967) Extraabdominal desmoids. A clinicopathological study. Ann Surg 170: 109-121 10 Enzinger FM, Weiss SW (1988) Soft Tissue Tumors. 2nd cd., CV Mosby, St. Louis 11 Friedlander ML, Hedley DW, Taylor IW (1984) Clinical and biological significance of aneuploidy in human tumours. ] Clin Pathol37: 961-974 12 Hajdu SI (1979) Pathology of Soft Tissue TUmors. Lea & Febiger, Philadelphia 13 Hunt RTN, Morgan HC, Ackerman LV (1960) Principles in the management of extraabdominal desmoids. Cancer 13: 825-836 14 Reiser M, Wiesmann W, Erlemann A, Härle A, Bohndorf K, Wuismann P, Kunze V, Peters PE (1988) Computertomographie und magnetische Resonanztomographie bei Weichteiltumoren. Orthopäde 17: 134-142 15 Sanchez L, Regh M, Biesterfeld S, Chatelain R, Böcking A (1990) Performance of a TV image analysis system as microdensitometer. Analyt Quant Cytol Histol 12: 279-284 16 Seckinger D, Sugarbaker E, Frankfurt 0 (1989) DNA conte nt in human cancer. Arch Pathol Lab Med 113:
619~626
17 Tehranzadeh J, Mnaymneh W, Ghavam C, Morillo G, Murphy BJ (1989) Comparison of CT and MR imaging in musculoskeletal neoplasms. ] Comp Assist Tomogr 13: 466-472
364 . ]. Sugar !8 Vanel D, Lacombe M], Couanet D, Kalifa C, Spielmann M, Genin] (1987) Musculosceletal tumors: Follow-up with MR imaging after treatment with surgery and radiation. Radiology 164: 243-245
!9 Weinstein EC, Payne WS, Soule EH (1963) Surgical treatment of desmoid tumor of the ehest wall. ] Thorae Surg 46: 242-251
Reeeived ]uly 17,1990· Accepted August 15, 1991
Key words: Soft tissue tumor - Leiomyosarcoma - Desmoid tumor - DNA cytometry - MR tomography Dr. med. L. Füzesi, Institut für Pathologie der RWTH Aachen, Pauwelsstr. 30, D-5100 Aachen, FRG
Letters to the Case J. Sugar Budapest, Hungary
It is not a rarity at all that two different tumours develop simultaneously or subsequently within the same region. From a diagnostic point of view it is more fortunate if the two tumours exhibit essential differences in histogenesis and histological structure. In this paper, however, the authors faced a knotty problem because: 1) Both belonged to the same group, i.e. they were of mesenchymal soft tissue origin, 2) The relatively less malignant desmoid tumour (DT) developed in the region of the highly malignant and metastasizing leiomyosarcoma (LS), soon after its surgical removal. The authors claim that these tumours developed subsequently and independently of each other. They think the inequality of the two tumours has to be verified by: 1) the different histological patterns, 2) the different immunohistochemical reactions and, 3) the different DNA cytometric values. In my letter to the case I try to outline - as usual in this journal- 1) wh at sort of more decisive arguments for the discrimination of the two tumours could been obtained and 2) to state whether the data provided by the authors are sufficient to prove their diagnoses. Based on the enclosed histologic picture the authors are right to think that in all probability the primary lesion corresponds to LS. As concerns its immunohistochemical behaviour it seems at present that while some LS-s are desmin negative, the presence of this marker excludes the diagnosis of fibrosarcoma or malignant fibrous histiocytoma (MFH) or myofibrosarcoma. It may happen that not all LS-s are positive for desmin. Miettinen lO observed
desmin positivity in 86-91 % of his LS cases. This value was, however, significantly lower in the study of Leader et al. 8 . It is fairly known that the intermediate filaments may contain identical epitopes that frequently lead to the coexpression of markers of the epithelium, muscles and connective tissue4 • Vimentin reacts not only with connective tissue but also with smooth muscle cells. Sometimes MFH mayaiso be positive for desmin. Positivity in these cases is probably attributable to myofibroblasts 7- 9 • I have mentioned these facts because desmin negativity and vimentin positivity of the second tumour (DT) do not exclude unequivocally the smooth muscle origin. Smooth muscle per se and most of the tumours arising from it are positive for anti-smooth muscle myosin!! and also for muscle actins. Therefore, desmin is not an absolute marker. In fact, muscle actins are at least as specific as desmin 9 • Several synonyms are in use for DT, for instance, desmoid fibromatosis, aggressive fibromatosis, infiltrative fibromatosis 6 . All these terms containing the word "fibromatosis" refer, in fact, to the richness of the intercellular matrix and ground substance in fibers and to the poor cellularity of the tumour. Naturally, DT-s mayaiso have some parts showing rich cellularity and bizarre neoplastic fibroblasts with 2-3 nuclei 6 • The enclosed figure can be accepted to demonstrate such a portion of DT. . DT-s are recurring and aggressive but not metastasizing fibroses. Consequently, they can be regarded as tumours of intermediate malignancy. I agree with the authors in that DNA morpho- and cytometry are helpful in judging malignancy. I was searching for some publications on the