- Email: [email protected]
Glomus tumor with diffuse infiltration of the quadriceps muscle: A case report
HUMAN PATHOLOGY
Volume 28, No, 6 (June 1997)
15. Bedi GC, Westra WH, Farzadegan H, et ah Microsatelliteinstability in primary neoplasms from HIV+ patients. Nat Med 1:65-68, 1995 16. Volpe G, Gamberi B, Pastore C, et al: Analysisofmicrosatellite instability in chronic lymphoproliferativedisorders. Ann HematoI 72:67-71, 1996 17. BaIlerini P, Gaidano G, Gong JZ, et aI: Multiple genetic lesions in
acquired immunodeficiencysyndrome-related non-Hodgkin lymphoma. Blood 81:166-176, 1993 18. Mao L, Lee DJ, Tockman MS, et al: Microsatellitealterations as clonal markers for the detection of human cancers. Proc Nail Acad Sci U S A 91:98719875, 1994
GLOMUS TUMOR WITH DIFFUSE INFILTRATION OF THE QUADRICEPS MUSCLE: A CASE REPORT GIOVANNI NEGRI, MD, MICHAEL SCHULTE,MD, AND WINFRIED MOHR, MD
A case of a diffuse growing giomus tumor with interstitial infiltration of the museulus vastus medialis and intermedius (quadriceps muscle) in a 21-year-old woman is reported. The tumor was diagnosed by needle biopsy and then removed with wide margins. The typical histological appearance and the immunohistochemical findings in the resected specimen confirmed the diagnosis. Histogenesis and the
biological behavior of giomus tumors are discussed. HUM PATHOL 28:750--752. Copyright © 1997 by W.B. Satmders Company Key words: glomus tumor; soft tissue neoplasms, immunohisto-
Since the clinical description of " p a i n f u l tubercles" by W o o d ~ and the histological analysis of Masson, 2 glomus tumors are known as well-circumscribed, small,and usually painful lesions. They are located preferentially in the d e e p dermis or subcutis of the extremities and often subungual. This lesion may arise elsewhere in the body and in regions where glomus bodies are not normally f o u n d or are rareP -s Unusual extracutaneous localizations can constitute a diagnostic p r o b l e m for the clinician, whereas the typical histological a p p e a r a n c e always makes a certain pathohistological diagnosis possible. To our knowledge, only few cases of diffuse infiltrating glomus tumors of the muscle have b e e n r e p o r t e d up to now. T M However, apart f r o m one case m e n t i o n e d by Enzinger and Weiss, 4 n o n e of these articles r e p o r t e d a growth behavior similar to o u r observation.
s e e m e d to be restricted to the walls of small-sized blood vessels just b e n e a t h the endothelial cells. No mitotic figures were present. T h e typical histological a p p e a r a n c e enabled us to diagnose a glomus tumor. T h e surgical specimen, resected 2 m o n t h s later, measured 22 × 11 × 6 cm and consisted in parts of the musculus vastus medialis and intermedius. Macroscopically, the e x a m i n a t i o n of the formalin-fixed s p e c i m e n showed musculature with only a diffuse rough cut surface. Apart f r o m some areas of fibrous tissue with ectatic b l o o d vessels, surprisingly, no t u m o r tissue was recognizable (Fig 1). Microscopically, a t u m o r tissue identical to the tissue observed in the biopsy interspersed the whole resected specimen. T u m o r cells infiltrated the interstitium without invasion of the muscle fibers (Fig 2). Sheets of r o u n d or polyhedral t u m o r cells with often relatively large nuclei, sometimes hyperchromatic, as well as binucleated and multinucleated cells s u r r o u n d e d preferentially small vessels which were lined with endothelial cells. No mitotic figures were observed. Furthermore, cavernous spaces, only partially s u r r o u n d e d by glomus cells, characterised o t h e r areas. T h e silver stain evidenced small fibrils a r o u n d the individual t u m o r cells. No periodic acid-Schiff (PAS) positivity was present. T h e i m m u n o h i s t o c h e m i c a l staining with muscle-specific actin (Biogenex [San Ramon, CA], m o n o c l o n a l ) desmin (DAKO [Copenhagen, Denmark], m o n o c l o n a l ) and vimentin (DAKO, m o n o c l o n a l ) showed strong reactivity in the majority of the t u m o r cells. Factor-VIII related antigen (DAKO) was restricted to the endothelial cells of the blood vessels, Ki-67 (Dianova [Hamburg, Germany], m o n o c l o n a l ) was positive in isolated t u m o r cells.
CASE R E P O R T A 21-year-old female patient c o m p l a i n i n g of pain ind u c e d by exposure to low temperatures and a m i n o r painful swelling of the left thigh, which she r e p o r t e d to have increased a little d u r i n g the previous 2 years, was referred to the departm e n t of Traumatology, H a n d and Reconstructive Surgery. Ultrasound e x a m i n a t i o n revealed a poorly defined i n h o m o g e nous hyperechoic lesion with high vascularization within the vastus medialis and intermedius portions of the quadriceps muscle. T h e high d e g r e e ofvascularisation was also c o n f i r m e d by magnetic resonance imaging (MRI). T h e r e was an elevated uptake in the blood pool of three-phase b o n e scan with no e n h a n c e m e n t d u r i n g the later phases. Glucose metabolism of the lesion as c o n f i r m e d by positron emission t o m o g r a p h y (PET) was n o t elevated. After histological e x a m i n a t i o n of the tissue s p e c i m e n taken by an a u t o m a t e d biopsy gun surgical resection with wide margins was p e r f o r m e d . T h e patient m a d e an uneventful recovery and was discharged after 8 days. P A T H O L O G I C A L FINDINGS T h e biopsy s p e c i m e n c o n t a i n e d skeletal muscle with interstitial infiltration by u n i f o r m t u m o r cells in few layers which
From the Institute of Pathology and Department of Traumatology, Hand- and Reconstructive Surgery of the University Ulm, Germany. Address correspondence and reprint requests to Prof. Dr. med. Winfried Mohr, Institute of Pathology of the University of Ulm, A1bert-Einstein-Allee 11, D-89081 Ulm, Germany. Copyright © 1997 by W.B. Saunders Company 0046-8177/97/2806-001355.00/0
750
chemistry. Abbreviations: MRI, magnetic resonance imaging; PET, positron emission tomography; PAS, periodic acid-Schiff.
DISCUSSION Only a few cases of diffuse infiltrating glomus t u m o r of the muscle have b e e n reported, and mainly in children. T M Overall, from the 685 cases of glomus t u m o r in adults reviewed by K o h o u t and Stout, 1° only 2 (0.3%) showed an infiltrative character. In a further 57 cases, diagnosed d u r i n g childhood, 7 (12%) were infiltrative, but n o n e localized in the d e e p soft tissues. G e r m a n 5 described a glomus t u m o r of the triceps muscle in an adult which, however, was encapsulated. Lumley and Stansfeld s r e p o r t e d a case in a 24-year-old w o m a n with infiltration of adipose tissue. F r o m the two cases described by W o o d and Dimmick,]l only one showed a partial infiltration of the muscle and both were in children and primary localized in the subcutis. F r o m the six cases r e p o r t e d by Gould et al, 9 two lesions were described as locally infiltrative glomus tumors, whereas
CASE STUDIES
FIGURE 1. (A) View of the c o m p l e t e resection specimen, (B) Detail from (A), (arrow): fibrous area with ectatic vessels.
the o t h e r f o u r displayed cytological atypias and were classified as glomangiosarcomas. However, the existence of this extremely rare m a l i g n a n t counterpart, in which a typical differentiated glomus t u m o r coexists with areas resembling a sarcoma, is controversial. N o n e of the few cases described 4'9~2 metastasized, and it therefore remains doubtful whether they represent true malignant tumors or not; however, an unusual m a l i g n a n t glomus t u m o r with widespread metastases was recently d e s c r i b e d ) 3 Overall, apart f r o m the case m e n t i o n e d by Enzinger and Weiss, 4 there is no further description of a case exhibiting histological features as n o t e d in our report. In our case, the
t u m o r cells showed relatively large and sometimes hyperchromatic nuclei, binucleated and multinucleated cells also occurred. Mitotic figures were absent. T h e i m m u n o h i s t o c h e m i cal reaction with Ki 67 c o n f i r m e d only a m i n i m a l rate of proliferation. However, the lesion was characterized by a m a r k e d infiltrative behavior: t u m o r tissue infiltrated the muscle interstitium diffusely and s e e m e d to extend within the wall of small and middle-sized vessels. This spreading of the t u m o r cells inside the walls of vessels may be i n t e r p r e t e d as a b e n i g n lesion with invasiveness restricted to the tissue of its origin. T h e histological appearance of the adjacent muscle cells was normal; n e i t h e r atrophy n o r t u m o r invasion was observed. T h e biological significance of glomus tumors is not completely understood. It is widely accepted that they arise from modified muscle cells which s u r r o u n d the arteriovenous anastomoses of the n o r m a l glomus body. 4 It remains uncertain whether the t u m o r represents a true neoplasm, hyperplasia, or even a hamartoma. Masson 2 i n t e r p r e t e d the lesion as a hyperplasia of the glomus body. Enzinger and Weiss 4 regard it rather as a neoplasm. T h e o c c u r r e n c e of glomus tumors also in locations where glomus bodies are rare or not present such as chest wall, 4 knee, ~° trachea, v and mediastinum 3 would exclude a hyperplasia and suggest rather a hamartoma. F r o m the literatur@ ° it becomes evident that most cases of infiltrating glomus tumors have arisen in childhood; however, our case was diagnosed in early adulthood. It c a n n o t be e x c l u d e d that the lesion was already present, although asymptomatic, in childhood; therefore, with regard to the age of the patient, a h a m a r t o m a c a n n o t be excluded. The slight increase of the t u m o r volume d u r i n g the last 2 years nevertheless indicates the manifestation of a true t u m o r and n o t a hamartoma. Apart f r o m the theories c o n c e r n i n g the biological significance we believe that, although rare, the glomus t u m o r should be considered as differential diagnosis of slow-growing, diffuse infiltrating, and highly vascularized tumors. As shown by our case, a minimal invasive bioptical diagnostic can be sufficient to achieve a correct classification of this lesion. Minimal invasive histological diagnostic constitutes a general p r o b l e m with malignant soft tissue neoplasms. T h e often m a r k e d m o r p h o l o g i c a l h e t e r o g e n e i t y of these tumors frequently does not allow a sure evaluation of the biological behaviour. However, a correct classification is a condition for an adequate therapy. An overestimation of the biological
FIGURE 2. (A) Ectatic b l o o d vessel wall and interstitial tissue of the muscle infiltrated with uniform tumor cells. (Hematoxylin-eosin stain; original magnification × 55.) (B) Detail from (A), (arrow): vessel wall infiltrated with tumor cells, (Hematoxylin-eosin stain; original magnification x 145.)
751
HUMAN PATHOLOGY Volume28, No. 6 (June 1997) b e h a v i o r c a n result in a n u n n e c e s s a r i l y wide r e s e c t i o n followed by serious f u n c t i o n a l limitations. REFERENCES 1. Wood W: On painful subcutaneous mbercIe. Ed Med SurgJ 8:283-291, 1812 2. Masson P: Le glomus neuromyo-arttrieI des rtgions tactiles et ses tumeurs. Lyon Chir, 21:257-280, 1924 3. Brindley GV: Glomus tumor of the mediastinum. J Thor Surg 18:417420, 1949 4. Enzinger FM, Weiss SW: Soft Tissue Tumors (ed 3). St. Louis, MO, Mosby, 1995, pp 701-713 5. German WM: Glomus tumor of the triceps muscle. Am J Clin Pathol 15:199-201, 1945 6. Hayes M, Van der Westhuitzen N, Holden GP: Aggressiveglomus tumor
of the nasal region. Report of a case with multiple local recurrences. Arch PathoI Lab Med 117:649-652, 1993 7. Kim Y, KimJH, Suh J-S, et al: Glomus rumor of the trachea. Report of a case with ultrastructural obselazations. Cancer 64:881-886, 1989 8. LumleyJSP, Stansfeld AG: Infiltrating glomus tumor of the lower limb. Br MedJ 1:484-485, 1972 9. Gould EW, Manivel JC, Albores-SaavedraJ, et al: Locally infiltrative glonms tumors and glomangiosarcomas. A clinical, uhrastructural, and immunohistochemical study. Cancer 65:310-318, 1990 10. Kohout E, Stout AP: The glomus tumor in children. Cancer 14:555566, 1961 11. Wood WS, Dimmick JE: Multiple infiltrating glomus tumors in children. Cancer 40:1680-1685, 1977 12. Aiba M, HirayamaA, KuramochiS: Glomangiosarcomain a glomus Ummr. An immunohistochemicaland ultrastrucmralstudy. Cancer 61:1467-1471, 1988 13. Brathwaite CD, Poppiti RJ: Malignant glomus tumor. A case report of widespread metastases in a patient with multiple gloums body hamartomas. Am J Surg Pathol 20:233-238, 1996
CORRESPONDENCE T h e AFIP a n d ARP have e s t a b l i s h e d a C e n t e r for Environm e n t a l P a t h o l o g y a n d Toxicology by e x p a n d i n g t h e Registry o f H u m a n Toxicology a n d t h e Registry o f Toxicologic Pathology for A n i m a l s (RTAP). T h e C e n t e r consists of a H u m a n Registry, t h e A n i m a l Registry, t h e I n t e r n a t i o n a l Data Base o n Toxic Lesions, a G e n e t i c Toxicology Laboratory, E x p e r t Panels o n Kidney, Liver a n d Lung, a n d a n E d u c a t i o n a l a n d R e s e a r c h c o m p o n e n t . T h e p r i n c i p a l goal o f t h e C e n t e r is to c o r r e l a t e k n o w l e d g e o n k n o w n a n i m a l m o d e l s o f disease a n d toxic m a r k e r s in a n i m a l s as they relate to h u m a n disease. A m a j o r mission of t h e C e n t e r is t h e d e v e l o p m e n t a n d i m p l e m e n t a t i o n of a n I n t e r n a t i o n a l Data Base for Toxic Lesions ( I N T O X ) in a n i m a l s a n d h u m a n s . H u m a n materials c u r r e n t l y available in this d a t a b a s e have b e e n derived f r o m t h e AFIP files c o n t a i n i n g m o r e t h a n 18,000 validated a n d s t a n d a r d i z e d cases. H u m a n materials c u r r e n t l y available in this d a t a b a s e have b e e n derived f r o m the AFIP files c o n t a i n i n g m o r e t h a n 18,000 validated a n d s t a n d a r d i z e d cases. A n i m a l d a t a available t h r o u g h o u t this d a t a b a s e i n c l u d e approximately 1,200 cases f r o m o u r Registry of V e t e r i n a r y Pathology, m a t e r i a l f r o m medical, d e n t a l a n d p h a r m a c y schools, data f r o m r e g u l a t o r y agencies s u b m i t t e d for review (FDA, EPA, N a t i o n a l Toxicology P r o g r a m ) as well as bioassay data f r o m pharmaceutical and chemical companies. T h e I n t e r n a t i o n a l Data Base for Toxic Lesions has b e e n o r g a n i z e d a r o u n d m o d u l e s r e p r e s e n t i n g sources a n d types of i n f o r m a t i o n . T h e m o d u l e s are first, h u m a n a n d a n i m a l data, followed by i n f o r m a t i o n f r o m studies o f c o n t r o l a n d experim e n t a l animals. A t h i r d m o d u l e consists o f access to p u b l i s h e d sources of i n f o r m a t i o n a n d lastly, o t h e r associated i n f o r m a tion w h i c h is n o t generally available t h r o u g h t h e p u b l i s h e d literature. Toxicology d a t a g a t h e r e d f r o m case collections o n h u m a n a n d a n i m a l studies is available in S N O M E D a n d SNOVET a n d N a t u r a l L a n g u a g e N o m e n c l a t u r e o n Oracle software with l i n k e d 486 p e r s o n a l c o m p u t e r s for easy a n d r a p i d access to t h e databases. T o m a i n t a i n t h e validation o f t h e case m a t e r i a l accessioned, t h e C e n t e r has b e e n able to set e x p e r t p a n e l s o f h u m a n a n d veterinary pathologists, a n d e p i d e m i o l o g i s t for t h e review o f h u m a n a n d a n i m a l toxicological studies, bioassay studies, a n d case materials s u b m i t t e d to the Center; a n d to provide e x p e r t advice o n t h e p o t e n t i a l h u m a n a n d a n i m a l toxicity o f new drugs. T h e s e e x p e r t p a n e l s were o r g a n i z e d to m a k e c e r t a i n t h a t t h e AFIP C e n t e r is able to address a b r o a d s p e c t r u m o f h u m a n h e a l t h p r o b l e m s r e l a t e d to the e n v i r o n m e n t . As a result, several r e s e a r c h projects a n d p r o g r a m s have b e e n o r g a n i z e d at t h e C e n t e r c o v e r i n g t h e following areas o f military a n d civilian medico-toxicologic interest:
G u i d e l i n e s f o r Letters Letters to t h e E d i t o r will b e p u b l i s h e d at t h e disc r e t i o n o f t h e e d i t o r as space p e r m i t s a n d are subject to e d i t i n g a n d a b r i d g e m e n t . T h e y s h o u l d b e typewritten, d o u b l e - s p a c e d , a n d s u b m i t t e d in triplicate. T h e y s h o u l d b e l i m i t e d to 500 words o r less a n d to n o m o r e t h a n five p e r t i n e n t references.
The Center for Environmental Pathology and Toxicology at the Armed Forces Institute of Pathology To the Editor:--In a r e c e n t editorial p u b l i s h e d in Human Pathology ( O c t o b e r 1996), D r B e r n a r d W a g n e r discussed t h e n e e d for t h e e s t a b l i s h m e n t o f a n a t i o n a l c e n t e r for t h e archival of e n v i r o n m e n t a l - r e l a t e d cases a n d collections of h u m a n a n d a n i m a l toxicological materials. ~ T h e a i m o f this c e n t e r w o u l d b e to d e v e l o p n a t i o n a l a n d i n t e r n a t i o n a l guidelines, to standardize, validate, a n d study e n v i r o n m e n t a l l y r e l a t e d diseases. This letter describes t h e efforts o f t h e A r m e d Forces Institute of P a t h o l o g y (AFIP) a n d t h e A m e r i c a n Registry of P a t h o l o g y (ARP) i n t h e d e v e l o p m e n t of a n e n v i r o n m e n t a l c e n t e r for t h e collection a n d study o f h u m a n a n d a n i m a l toxicological materials. W e o u t l i n e t h e d e s c r i p t i o n o f the center, c u r r e n t capabilities a n d f u t u r e activities with p a r t i c u l a r e m p h a s i s o n its role as a n archival c e n t e r for t h e study a n d r e s e a r c h o f e n v i r o n m e n t a l - r e l a t e d diseases. U n d e r s t a n d i n g t h e role o f t h e e n v i r o n m e n t o n the develo p m e n t o f h u m a n a n d a n i m a l diseases is o f pivotal i m p o r t a n c e in setting a c o o r d i n a t e d n a t i o n a l e n v i r o n m e n t a l h e a l t h a g e n d a . A l o n g with studies o n adverse d r u g reactions, envir o n m e n t a l l y r e l a t e d diseases are b e i n g n o w r e c o g n i z e d by t h e m o d e r n p a t h o l o g i s t a n d clinician, a n d i n c l u d e d as p a r t o f t h e differential diagnosis. A l t h o u g h t h e association of h u m a n disease a n d e x p o s u r e to c e r t a i n e n v i r o n m e n t a l agents includi n g arsenic, asbestos, dioxin, lead, m e r c u r y a n d o t h e r s have b e e n well studied; t h e r e are m a n y o t h e r e n v i r o n m e n t a l dise a s e - p r o d u c i n g agents o f industrial, p h a r m a c e u t i c a l , a n d ant h r o p o g e n i c origins t h a t have n o t b e s t u d i e d a n d h e n c e , t h e effect(s) o n h u m a n a n d a n i m a l h e a l t h are largely u n k n o w n . D e v e l o p m e n t o f archival materials b a s e d o n h u m a n a n d animal tissues r e l a t i n g to e n v i r o n m e n t a l diseases is n e e d e d to p r o v i d e i d e n t i f i c a t i o n of t h e causative agents a n d to d e v e l o p criteria for t h e i r a c c u r a t e c l i n i c o p a t h o l o g i c diagnosis.
752
Volume 28, No, 6 (June 1997)
15. Bedi GC, Westra WH, Farzadegan H, et ah Microsatelliteinstability in primary neoplasms from HIV+ patients. Nat Med 1:65-68, 1995 16. Volpe G, Gamberi B, Pastore C, et al: Analysisofmicrosatellite instability in chronic lymphoproliferativedisorders. Ann HematoI 72:67-71, 1996 17. BaIlerini P, Gaidano G, Gong JZ, et aI: Multiple genetic lesions in
acquired immunodeficiencysyndrome-related non-Hodgkin lymphoma. Blood 81:166-176, 1993 18. Mao L, Lee DJ, Tockman MS, et al: Microsatellitealterations as clonal markers for the detection of human cancers. Proc Nail Acad Sci U S A 91:98719875, 1994
GLOMUS TUMOR WITH DIFFUSE INFILTRATION OF THE QUADRICEPS MUSCLE: A CASE REPORT GIOVANNI NEGRI, MD, MICHAEL SCHULTE,MD, AND WINFRIED MOHR, MD
A case of a diffuse growing giomus tumor with interstitial infiltration of the museulus vastus medialis and intermedius (quadriceps muscle) in a 21-year-old woman is reported. The tumor was diagnosed by needle biopsy and then removed with wide margins. The typical histological appearance and the immunohistochemical findings in the resected specimen confirmed the diagnosis. Histogenesis and the
biological behavior of giomus tumors are discussed. HUM PATHOL 28:750--752. Copyright © 1997 by W.B. Satmders Company Key words: glomus tumor; soft tissue neoplasms, immunohisto-
Since the clinical description of " p a i n f u l tubercles" by W o o d ~ and the histological analysis of Masson, 2 glomus tumors are known as well-circumscribed, small,and usually painful lesions. They are located preferentially in the d e e p dermis or subcutis of the extremities and often subungual. This lesion may arise elsewhere in the body and in regions where glomus bodies are not normally f o u n d or are rareP -s Unusual extracutaneous localizations can constitute a diagnostic p r o b l e m for the clinician, whereas the typical histological a p p e a r a n c e always makes a certain pathohistological diagnosis possible. To our knowledge, only few cases of diffuse infiltrating glomus tumors of the muscle have b e e n r e p o r t e d up to now. T M However, apart f r o m one case m e n t i o n e d by Enzinger and Weiss, 4 n o n e of these articles r e p o r t e d a growth behavior similar to o u r observation.
s e e m e d to be restricted to the walls of small-sized blood vessels just b e n e a t h the endothelial cells. No mitotic figures were present. T h e typical histological a p p e a r a n c e enabled us to diagnose a glomus tumor. T h e surgical specimen, resected 2 m o n t h s later, measured 22 × 11 × 6 cm and consisted in parts of the musculus vastus medialis and intermedius. Macroscopically, the e x a m i n a t i o n of the formalin-fixed s p e c i m e n showed musculature with only a diffuse rough cut surface. Apart f r o m some areas of fibrous tissue with ectatic b l o o d vessels, surprisingly, no t u m o r tissue was recognizable (Fig 1). Microscopically, a t u m o r tissue identical to the tissue observed in the biopsy interspersed the whole resected specimen. T u m o r cells infiltrated the interstitium without invasion of the muscle fibers (Fig 2). Sheets of r o u n d or polyhedral t u m o r cells with often relatively large nuclei, sometimes hyperchromatic, as well as binucleated and multinucleated cells s u r r o u n d e d preferentially small vessels which were lined with endothelial cells. No mitotic figures were observed. Furthermore, cavernous spaces, only partially s u r r o u n d e d by glomus cells, characterised o t h e r areas. T h e silver stain evidenced small fibrils a r o u n d the individual t u m o r cells. No periodic acid-Schiff (PAS) positivity was present. T h e i m m u n o h i s t o c h e m i c a l staining with muscle-specific actin (Biogenex [San Ramon, CA], m o n o c l o n a l ) desmin (DAKO [Copenhagen, Denmark], m o n o c l o n a l ) and vimentin (DAKO, m o n o c l o n a l ) showed strong reactivity in the majority of the t u m o r cells. Factor-VIII related antigen (DAKO) was restricted to the endothelial cells of the blood vessels, Ki-67 (Dianova [Hamburg, Germany], m o n o c l o n a l ) was positive in isolated t u m o r cells.
CASE R E P O R T A 21-year-old female patient c o m p l a i n i n g of pain ind u c e d by exposure to low temperatures and a m i n o r painful swelling of the left thigh, which she r e p o r t e d to have increased a little d u r i n g the previous 2 years, was referred to the departm e n t of Traumatology, H a n d and Reconstructive Surgery. Ultrasound e x a m i n a t i o n revealed a poorly defined i n h o m o g e nous hyperechoic lesion with high vascularization within the vastus medialis and intermedius portions of the quadriceps muscle. T h e high d e g r e e ofvascularisation was also c o n f i r m e d by magnetic resonance imaging (MRI). T h e r e was an elevated uptake in the blood pool of three-phase b o n e scan with no e n h a n c e m e n t d u r i n g the later phases. Glucose metabolism of the lesion as c o n f i r m e d by positron emission t o m o g r a p h y (PET) was n o t elevated. After histological e x a m i n a t i o n of the tissue s p e c i m e n taken by an a u t o m a t e d biopsy gun surgical resection with wide margins was p e r f o r m e d . T h e patient m a d e an uneventful recovery and was discharged after 8 days. P A T H O L O G I C A L FINDINGS T h e biopsy s p e c i m e n c o n t a i n e d skeletal muscle with interstitial infiltration by u n i f o r m t u m o r cells in few layers which
From the Institute of Pathology and Department of Traumatology, Hand- and Reconstructive Surgery of the University Ulm, Germany. Address correspondence and reprint requests to Prof. Dr. med. Winfried Mohr, Institute of Pathology of the University of Ulm, A1bert-Einstein-Allee 11, D-89081 Ulm, Germany. Copyright © 1997 by W.B. Saunders Company 0046-8177/97/2806-001355.00/0
750
chemistry. Abbreviations: MRI, magnetic resonance imaging; PET, positron emission tomography; PAS, periodic acid-Schiff.
DISCUSSION Only a few cases of diffuse infiltrating glomus t u m o r of the muscle have b e e n reported, and mainly in children. T M Overall, from the 685 cases of glomus t u m o r in adults reviewed by K o h o u t and Stout, 1° only 2 (0.3%) showed an infiltrative character. In a further 57 cases, diagnosed d u r i n g childhood, 7 (12%) were infiltrative, but n o n e localized in the d e e p soft tissues. G e r m a n 5 described a glomus t u m o r of the triceps muscle in an adult which, however, was encapsulated. Lumley and Stansfeld s r e p o r t e d a case in a 24-year-old w o m a n with infiltration of adipose tissue. F r o m the two cases described by W o o d and Dimmick,]l only one showed a partial infiltration of the muscle and both were in children and primary localized in the subcutis. F r o m the six cases r e p o r t e d by Gould et al, 9 two lesions were described as locally infiltrative glomus tumors, whereas
CASE STUDIES
FIGURE 1. (A) View of the c o m p l e t e resection specimen, (B) Detail from (A), (arrow): fibrous area with ectatic vessels.
the o t h e r f o u r displayed cytological atypias and were classified as glomangiosarcomas. However, the existence of this extremely rare m a l i g n a n t counterpart, in which a typical differentiated glomus t u m o r coexists with areas resembling a sarcoma, is controversial. N o n e of the few cases described 4'9~2 metastasized, and it therefore remains doubtful whether they represent true malignant tumors or not; however, an unusual m a l i g n a n t glomus t u m o r with widespread metastases was recently d e s c r i b e d ) 3 Overall, apart f r o m the case m e n t i o n e d by Enzinger and Weiss, 4 there is no further description of a case exhibiting histological features as n o t e d in our report. In our case, the
t u m o r cells showed relatively large and sometimes hyperchromatic nuclei, binucleated and multinucleated cells also occurred. Mitotic figures were absent. T h e i m m u n o h i s t o c h e m i cal reaction with Ki 67 c o n f i r m e d only a m i n i m a l rate of proliferation. However, the lesion was characterized by a m a r k e d infiltrative behavior: t u m o r tissue infiltrated the muscle interstitium diffusely and s e e m e d to extend within the wall of small and middle-sized vessels. This spreading of the t u m o r cells inside the walls of vessels may be i n t e r p r e t e d as a b e n i g n lesion with invasiveness restricted to the tissue of its origin. T h e histological appearance of the adjacent muscle cells was normal; n e i t h e r atrophy n o r t u m o r invasion was observed. T h e biological significance of glomus tumors is not completely understood. It is widely accepted that they arise from modified muscle cells which s u r r o u n d the arteriovenous anastomoses of the n o r m a l glomus body. 4 It remains uncertain whether the t u m o r represents a true neoplasm, hyperplasia, or even a hamartoma. Masson 2 i n t e r p r e t e d the lesion as a hyperplasia of the glomus body. Enzinger and Weiss 4 regard it rather as a neoplasm. T h e o c c u r r e n c e of glomus tumors also in locations where glomus bodies are rare or not present such as chest wall, 4 knee, ~° trachea, v and mediastinum 3 would exclude a hyperplasia and suggest rather a hamartoma. F r o m the literatur@ ° it becomes evident that most cases of infiltrating glomus tumors have arisen in childhood; however, our case was diagnosed in early adulthood. It c a n n o t be e x c l u d e d that the lesion was already present, although asymptomatic, in childhood; therefore, with regard to the age of the patient, a h a m a r t o m a c a n n o t be excluded. The slight increase of the t u m o r volume d u r i n g the last 2 years nevertheless indicates the manifestation of a true t u m o r and n o t a hamartoma. Apart f r o m the theories c o n c e r n i n g the biological significance we believe that, although rare, the glomus t u m o r should be considered as differential diagnosis of slow-growing, diffuse infiltrating, and highly vascularized tumors. As shown by our case, a minimal invasive bioptical diagnostic can be sufficient to achieve a correct classification of this lesion. Minimal invasive histological diagnostic constitutes a general p r o b l e m with malignant soft tissue neoplasms. T h e often m a r k e d m o r p h o l o g i c a l h e t e r o g e n e i t y of these tumors frequently does not allow a sure evaluation of the biological behaviour. However, a correct classification is a condition for an adequate therapy. An overestimation of the biological
FIGURE 2. (A) Ectatic b l o o d vessel wall and interstitial tissue of the muscle infiltrated with uniform tumor cells. (Hematoxylin-eosin stain; original magnification × 55.) (B) Detail from (A), (arrow): vessel wall infiltrated with tumor cells, (Hematoxylin-eosin stain; original magnification x 145.)
751
HUMAN PATHOLOGY Volume28, No. 6 (June 1997) b e h a v i o r c a n result in a n u n n e c e s s a r i l y wide r e s e c t i o n followed by serious f u n c t i o n a l limitations. REFERENCES 1. Wood W: On painful subcutaneous mbercIe. Ed Med SurgJ 8:283-291, 1812 2. Masson P: Le glomus neuromyo-arttrieI des rtgions tactiles et ses tumeurs. Lyon Chir, 21:257-280, 1924 3. Brindley GV: Glomus tumor of the mediastinum. J Thor Surg 18:417420, 1949 4. Enzinger FM, Weiss SW: Soft Tissue Tumors (ed 3). St. Louis, MO, Mosby, 1995, pp 701-713 5. German WM: Glomus tumor of the triceps muscle. Am J Clin Pathol 15:199-201, 1945 6. Hayes M, Van der Westhuitzen N, Holden GP: Aggressiveglomus tumor
of the nasal region. Report of a case with multiple local recurrences. Arch PathoI Lab Med 117:649-652, 1993 7. Kim Y, KimJH, Suh J-S, et al: Glomus rumor of the trachea. Report of a case with ultrastructural obselazations. Cancer 64:881-886, 1989 8. LumleyJSP, Stansfeld AG: Infiltrating glomus tumor of the lower limb. Br MedJ 1:484-485, 1972 9. Gould EW, Manivel JC, Albores-SaavedraJ, et al: Locally infiltrative glonms tumors and glomangiosarcomas. A clinical, uhrastructural, and immunohistochemical study. Cancer 65:310-318, 1990 10. Kohout E, Stout AP: The glomus tumor in children. Cancer 14:555566, 1961 11. Wood WS, Dimmick JE: Multiple infiltrating glomus tumors in children. Cancer 40:1680-1685, 1977 12. Aiba M, HirayamaA, KuramochiS: Glomangiosarcomain a glomus Ummr. An immunohistochemicaland ultrastrucmralstudy. Cancer 61:1467-1471, 1988 13. Brathwaite CD, Poppiti RJ: Malignant glomus tumor. A case report of widespread metastases in a patient with multiple gloums body hamartomas. Am J Surg Pathol 20:233-238, 1996
CORRESPONDENCE T h e AFIP a n d ARP have e s t a b l i s h e d a C e n t e r for Environm e n t a l P a t h o l o g y a n d Toxicology by e x p a n d i n g t h e Registry o f H u m a n Toxicology a n d t h e Registry o f Toxicologic Pathology for A n i m a l s (RTAP). T h e C e n t e r consists of a H u m a n Registry, t h e A n i m a l Registry, t h e I n t e r n a t i o n a l Data Base o n Toxic Lesions, a G e n e t i c Toxicology Laboratory, E x p e r t Panels o n Kidney, Liver a n d Lung, a n d a n E d u c a t i o n a l a n d R e s e a r c h c o m p o n e n t . T h e p r i n c i p a l goal o f t h e C e n t e r is to c o r r e l a t e k n o w l e d g e o n k n o w n a n i m a l m o d e l s o f disease a n d toxic m a r k e r s in a n i m a l s as they relate to h u m a n disease. A m a j o r mission of t h e C e n t e r is t h e d e v e l o p m e n t a n d i m p l e m e n t a t i o n of a n I n t e r n a t i o n a l Data Base for Toxic Lesions ( I N T O X ) in a n i m a l s a n d h u m a n s . H u m a n materials c u r r e n t l y available in this d a t a b a s e have b e e n derived f r o m t h e AFIP files c o n t a i n i n g m o r e t h a n 18,000 validated a n d s t a n d a r d i z e d cases. H u m a n materials c u r r e n t l y available in this d a t a b a s e have b e e n derived f r o m the AFIP files c o n t a i n i n g m o r e t h a n 18,000 validated a n d s t a n d a r d i z e d cases. A n i m a l d a t a available t h r o u g h o u t this d a t a b a s e i n c l u d e approximately 1,200 cases f r o m o u r Registry of V e t e r i n a r y Pathology, m a t e r i a l f r o m medical, d e n t a l a n d p h a r m a c y schools, data f r o m r e g u l a t o r y agencies s u b m i t t e d for review (FDA, EPA, N a t i o n a l Toxicology P r o g r a m ) as well as bioassay data f r o m pharmaceutical and chemical companies. T h e I n t e r n a t i o n a l Data Base for Toxic Lesions has b e e n o r g a n i z e d a r o u n d m o d u l e s r e p r e s e n t i n g sources a n d types of i n f o r m a t i o n . T h e m o d u l e s are first, h u m a n a n d a n i m a l data, followed by i n f o r m a t i o n f r o m studies o f c o n t r o l a n d experim e n t a l animals. A t h i r d m o d u l e consists o f access to p u b l i s h e d sources of i n f o r m a t i o n a n d lastly, o t h e r associated i n f o r m a tion w h i c h is n o t generally available t h r o u g h t h e p u b l i s h e d literature. Toxicology d a t a g a t h e r e d f r o m case collections o n h u m a n a n d a n i m a l studies is available in S N O M E D a n d SNOVET a n d N a t u r a l L a n g u a g e N o m e n c l a t u r e o n Oracle software with l i n k e d 486 p e r s o n a l c o m p u t e r s for easy a n d r a p i d access to t h e databases. T o m a i n t a i n t h e validation o f t h e case m a t e r i a l accessioned, t h e C e n t e r has b e e n able to set e x p e r t p a n e l s o f h u m a n a n d veterinary pathologists, a n d e p i d e m i o l o g i s t for t h e review o f h u m a n a n d a n i m a l toxicological studies, bioassay studies, a n d case materials s u b m i t t e d to the Center; a n d to provide e x p e r t advice o n t h e p o t e n t i a l h u m a n a n d a n i m a l toxicity o f new drugs. T h e s e e x p e r t p a n e l s were o r g a n i z e d to m a k e c e r t a i n t h a t t h e AFIP C e n t e r is able to address a b r o a d s p e c t r u m o f h u m a n h e a l t h p r o b l e m s r e l a t e d to the e n v i r o n m e n t . As a result, several r e s e a r c h projects a n d p r o g r a m s have b e e n o r g a n i z e d at t h e C e n t e r c o v e r i n g t h e following areas o f military a n d civilian medico-toxicologic interest:
G u i d e l i n e s f o r Letters Letters to t h e E d i t o r will b e p u b l i s h e d at t h e disc r e t i o n o f t h e e d i t o r as space p e r m i t s a n d are subject to e d i t i n g a n d a b r i d g e m e n t . T h e y s h o u l d b e typewritten, d o u b l e - s p a c e d , a n d s u b m i t t e d in triplicate. T h e y s h o u l d b e l i m i t e d to 500 words o r less a n d to n o m o r e t h a n five p e r t i n e n t references.
The Center for Environmental Pathology and Toxicology at the Armed Forces Institute of Pathology To the Editor:--In a r e c e n t editorial p u b l i s h e d in Human Pathology ( O c t o b e r 1996), D r B e r n a r d W a g n e r discussed t h e n e e d for t h e e s t a b l i s h m e n t o f a n a t i o n a l c e n t e r for t h e archival of e n v i r o n m e n t a l - r e l a t e d cases a n d collections of h u m a n a n d a n i m a l toxicological materials. ~ T h e a i m o f this c e n t e r w o u l d b e to d e v e l o p n a t i o n a l a n d i n t e r n a t i o n a l guidelines, to standardize, validate, a n d study e n v i r o n m e n t a l l y r e l a t e d diseases. This letter describes t h e efforts o f t h e A r m e d Forces Institute of P a t h o l o g y (AFIP) a n d t h e A m e r i c a n Registry of P a t h o l o g y (ARP) i n t h e d e v e l o p m e n t of a n e n v i r o n m e n t a l c e n t e r for t h e collection a n d study o f h u m a n a n d a n i m a l toxicological materials. W e o u t l i n e t h e d e s c r i p t i o n o f the center, c u r r e n t capabilities a n d f u t u r e activities with p a r t i c u l a r e m p h a s i s o n its role as a n archival c e n t e r for t h e study a n d r e s e a r c h o f e n v i r o n m e n t a l - r e l a t e d diseases. U n d e r s t a n d i n g t h e role o f t h e e n v i r o n m e n t o n the develo p m e n t o f h u m a n a n d a n i m a l diseases is o f pivotal i m p o r t a n c e in setting a c o o r d i n a t e d n a t i o n a l e n v i r o n m e n t a l h e a l t h a g e n d a . A l o n g with studies o n adverse d r u g reactions, envir o n m e n t a l l y r e l a t e d diseases are b e i n g n o w r e c o g n i z e d by t h e m o d e r n p a t h o l o g i s t a n d clinician, a n d i n c l u d e d as p a r t o f t h e differential diagnosis. A l t h o u g h t h e association of h u m a n disease a n d e x p o s u r e to c e r t a i n e n v i r o n m e n t a l agents includi n g arsenic, asbestos, dioxin, lead, m e r c u r y a n d o t h e r s have b e e n well studied; t h e r e are m a n y o t h e r e n v i r o n m e n t a l dise a s e - p r o d u c i n g agents o f industrial, p h a r m a c e u t i c a l , a n d ant h r o p o g e n i c origins t h a t have n o t b e s t u d i e d a n d h e n c e , t h e effect(s) o n h u m a n a n d a n i m a l h e a l t h are largely u n k n o w n . D e v e l o p m e n t o f archival materials b a s e d o n h u m a n a n d animal tissues r e l a t i n g to e n v i r o n m e n t a l diseases is n e e d e d to p r o v i d e i d e n t i f i c a t i o n of t h e causative agents a n d to d e v e l o p criteria for t h e i r a c c u r a t e c l i n i c o p a t h o l o g i c diagnosis.
752