These soft tissue tumors are one of the most common fibrous tumors occurring in infancy and childhood. Nontheless, when examining all tumors, these are relatively rare neoplasms. They arise either as solitary tumors or multicentric ones. Although histologically banal, multicentric tumors may cause considerable morbidity and in some cases death.
Epidemiology Disease Associations Pathogenesis Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/Immunohistochemistry/Electron Microscopy Differential Diagnosis Prognosis and Treatment Commonly Used Terms
EPIDEMIOLOGY CHARACTERIZATION SYNONYMS Infantile myofibromatosis INCIDENCE Most common fibrous tumor of infancy and childhood AGE RANGE-MEDIAN Usually infancy and childhood but adult case have been reported. SEX (M:F) Male predominance
DISEASE ASSOCIATIONS CHARACTERIZATION MULTI-ORGAN MALFORMATIONS
Major malformations in a case of infantile myofibromatosis.
Michel M, Ninane J, Claus D, Gosseye S, Wese FX, Moulin D.
Department of Paediatrics, Cliniques Universitaires Saint-Luc, Brussels, Belgium
Eur J Pediatr 1990 Jan;149(4):251-2 Abstract quote
A case of infantile myofibromatosis associated with oesophageal atresia, annular pancreas, additional sacral vertebra and hypoplatic right kidney in a male neonate is reported. The possibility of associated malformations in this rare disease is outlined.
PATHOGENESIS CHARACTERIZATION APOPTOSIS
Massive apoptosis in infantile myofibromatosis. A putative mechanism of tumor regression.
Fukasawa Y, Ishikura H, Takada A, Yokoyama S, Imamura M, Yoshiki T, Sato H.
Department of Pathology, Sapporo City General Hospital, Japan.
Am J Pathol 1994 Mar;144(3):480-5 Abstract quote
Two cases of solitary infantile myofibromatosis (IM) are presented. Solitary IM are tumors prone to spontaneous regression. Histopathologically, several tumor lobules in our IM cases had central areas of massive cell death, with nuclear pyknosis, cytoplasmic hyalinization and nuclear fragmentation but without lymphoid or neutrophilic cell infiltration.
These central cell death areas consisted of about 40% in case 2 and 50% in case 1 of the entire tumor tissues, respectively. Electron microscopy revealed that the condensed nuclei and cytoplasm were fragmented into "apoptotic bodies", with or without phagocytosis by histiocytes. DNA fragmentation, as evidenced by the terminal deoxy transferase-mediated uptake of biotinylated dUTP, was identified at massive cell death areas on paraffin sections from both cases. A characteristic 180- to 190-bp nucleosomal ladder was detected in DNA obtained from the tumor cells in case 1. The collective evidence suggested that these tumors underwent a central, massive apoptosis.
As massive cell death similar to that seen in the present cases has been described in other documented cases of IM, we propose that the spontaneous regression that frequently occurs with this type of tumor may be mediated by massive apoptotic cell death.
del(6)(q12q15) as the sole cytogenetic anomaly in a case of solitary infantile myofibromatosis.
Stenman G, Nadal N, Persson S, Gunterberg B, Angervall L.
Lundberg Laboratory for Cancer Research, Department of Pathology, Goteborg University, Sahlgrenska University Hospital, SE-413 45 Goteborg, Sweden.
Oncol Rep 1999 Sep-Oct;6(5):1101-4 Abstract quote
We describe a case of light microscopically typical solitary, infantile myofibromatosis in a 6-month old boy. The myofibroblastic differentiation of the tumor was supported by immunohistochemical and ultrastructural analyses. Cytogenetic and FISH analyses revealed a pseudodiploid karyotype with an interstitial deletion of the long arm of one chromosome 6, del(6)(q12q15), as the sole anomaly.
The results demonstrate the usefulness of cytogenetics and FISH in distinguishing this type of lesion from infantile fibrosarcoma. To the best of our knowledge this is the first cytogenetic analysis of solitary infantile myofibromatosis.
Johnson GL, Baisden BL, Fishman EK.
Russel H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Skeletal Radiol 1997 Oct;26(10):611-4 Abstract quote
Infantile myofibromatosis is a mesenchymal tumor most commonly seen in infancy. The tumors have a variable appearance on CT/MR and often simulate a more aggressive neoplasm.
This report describes CT/MR findings in cases of infantile myofibromatosis with pathologic correlation. Discussion into the success of imaging in suggesting the correct diagnosis is also addressed.
Self-healing generalized infantile myofibromatosis with elevated urinary bFGF.
Leaute-Labreze C, Labarthe MP, Blanc JF, Sanyas P, Dosquet C, Taieb A.
Department of Pediatric Dermatology, Pellegrin Hospital, Bordeaux, France.
Pediatr Dermatol 2001 Jul-Aug;18(4):305-7 Abstract quote
We report a case of generalized infantile myofibromatosis with favorable outcome despite systemic involvement. Elevated urinary bFGF levels during the active phase of the disease suggested an angiogenic stimulation in the pathogenesis of myofibromatosis.
CHARACTERIZATION GENERAL VARIANTS CONGENITAL
Congenital generalized myofibromatosis: a disseminated angiocentric myofibromatosis.
Coffin CM, Neilson KA, Ingels S, Frank-Gerszberg R, Dehner LP.
Lauren V. Ackerman Division of Surgical Pathology, Barnes Children's Hospital, St. Louis, Missouri, USA.
Pediatr Pathol Lab Med 1995 Jul-Aug;15(4):571-87 Abstract quote
Infantile myofibromatosis occurs in solitary, multiple, and generalized forms, with similar histology but different clinicopathologic and prognostic implications.
We report the findings in two male infants with fatal congenital generalized myofibromatosis (CGMF) who presented with multiple dermal and subcutaneous nodules at birth. Imaging studies revealed bony and visceral lesions, which progressed despite chemotherapy. One infant had severe hypercalcemia associated with extensive lytic bone lesions.
Both infants died in respiratory failure and had a combination of pulmonary CGMF and diffuse alveolar damage. Involvement of skin, soft tissue, bone, heart, lungs, liver, gastrointestinal tract, and endocrine organs was confirmed at autopsy in each case. A consistent histologic pattern of interlacing fascicles of myofibroblasts with abundant eosinophilic cytoplasm was noted, with variable necrosis and calcifications in some sites. The myofibroblasts displayed vimentin and smooth muscle actin immunoreactivity. The lungs in each case had the presumably early lesions of CGMF with an angiocentric and perivascular growth of myofibroblasts. A similar vascular pattern was present in all affected organs.
These two cases demonstrate the extraordinary presentation of CGMF, which suggests its multifocal origin from vascular subintimal mesenchymal or smooth muscle cells whose phenotype is that of myofibroblasts.
Infantile myofibromatosis. Report of two cases in one family.
Venencie PY, Bigel P, Desgruelles C, Lortat-Jacob S, Dufier JL, Saurat JH.
Dermatology Unit, Centre Hospitalier de Bicetre, France.
Br J Dermatol 1987 Aug;117(2):255-9 Abstract quote
Two brothers with infantile myofibromatosis are reported. Both had cutaneous and skeletal myofibromas with spontaneous and complete healing of their cutaneous lesions. These cases suggest autosomal recessive inheritance of this rare disorder.
Familial occurrence of infantile myofibromatosis.
Bracko M, Cindro L, Golouh R.
Department of Pathology, Institute of Oncology, Ljubljana, Slovenia.
Cancer 1992 Mar 1;69(5):1294-9 Abstract quote
Two brothers with multicentric infantile myofibromatosis (IM) are reported. In both, tumors were present at birth; the tumors regressed spontaneously, but new lesions developed throughout the follow-up periods of 15 and 8 years.
Immunohistochemically, the nodules were found to be positive for vimentin and actin, but negative for desmin and S-100 protein; these findings support the myofibroblastic nature of IM. A literature review revealed nine additional families with IM in more than one family member.
Although the occurrence of IM in eight sets of siblings, with consanguinity in two of them, favors an autosomal recessive mode of inheritance, the disorder also has been well documented in half-sisters and in successive generations, which makes autosomal dominant inheritance a more plausible explanation.
HEAD AND NECK
Solitary infantile and adult myofibromatosis of the nasal cavity: a report of two cases.
Walsh RM, Leen EJ, Gleeson MJ.
Department of Otolaryngology, Guys Hospital, London, UK.
J Laryngol Otol 1996 Jun;110(6):574-7 Abstract quote
Myofibromatosis is an uncommon, usually cutaneous, condition in which there is a benign proliferation of myofibroblasts.
Solitary and multicentric nodular forms with, and without, visceral involvement have been described. Infantile and adult sub-types have been reported, each having distinct clinicopathological features. Presentation in the head and neck is common. It is frequently misdiagnosed because of its peculiar histological features.
The first documented cases of infantile and adult myofibromatosis involving the nasal cavity are reported.
Multicentric infantile myofibromatosis in the cranium: case report.
Hasegawa M, Kida S, Yamashima T, Yamashita J, Takakuwa S.
Department of Neurosurgery, Kanazawa University School of Medicine, Japan.
Neurosurgery 1995 Jun;36(6):1200-3 Abstract quote
Infantile myofibromatosis is a rare clinical entity characterized by multiple mesenchymal tumors in the neonatal period.
We describe a 15-month-old girl with multicentric cranial lesions involving the parietal and occipital bones associated with a single small subcutaneous lesion in the back. Magnetic resonance imaging clearly demonstrated the isointense lesions on T1-, T2-, and proton density-weighted images, which showed marked gadolinium enhancement of the tumors and adjacent dura mater. A histological examination of the resected temporal lesion revealed the myofibroblastic nature of the tumor cells. This is the first description of magnetic resonance features of multicentric infantile myofibromatosis in the cranium, and gadolinium-enhanced magnetic resonance images were useful in showing dural involvement.
The importance of recognizing this disorder is emphasized because of its special clinical behavior.
Intracranial infantile myofibromatosis with intraparenchymal involvement.
Kaplan SS, Ojemann JG, Grange DK, Fuller C, Park TS.
Department of Neurological Surgery, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, Mo., USA.
Pediatr Neurosurg 2002 Apr;36(4):214-7 Abstract quote
Infantile myofibromatosis is the most common fibrous disorder of infancy and early childhood. Intracranial involvement is rare, with the majority of lesions being localized to the skull or dura with variable intracranial extension.
We present the case of a 19-month-old girl with infantile myofibromatosis and an incidentally discovered, enlarging, calcified, posterior fossa mass. The patient underwent suboccipital craniotomy and resection of the lesion. This is the first report of the surgical removal of an intraparenchymal infantile myofibroma.
Multicentric infantile myofibromatosis.
Behar PM, Albritton FD, Muller S, Todd NW.
Department of Otolaryngology-Head and Neck Surgery, Emory University, Atlanta, GA 30322, USA.
Int J Pediatr Otorhinolaryngol 1998 Oct 15;45(3):249-54 Abstract quote
Infantile myofibromatosis (IM) is a rare tumor of infancy and childhood, typically presenting as a firm, nodular mass involving soft tissue, bone or viscera. Approximately one-third of cases involve the head and neck. These tumors can be solitary or multicentric. Biopsy reveals tumor cells that resemble myofibroblasts. Spontaneous regression may occur.
A high degree of suspicion is necessary to differentiate this entity from other more aggressive processes histiocytosis, fibrosarcoma, rhabdomyosarcoma.
We describe the case of a male infant with multicentric myofibromatosis, presenting with multiple thoraco-abdominal subcutaneous nodules and lytic mass lesions of the temporal bone and calvarium. The characteristic clinical, radiologic and histopathologic features of this process are reviewed along with diagnostic and therapeutic options.
Infantile myofibromatosis: a case study and review of literature.
Giannakopoulou C, Hatzidaki E, Giannakopoulos K, Matalliotakis I, Koumantakis E, Kalmanti M.
Department of Neonatology, Children of the University of Crete, Greece.
J Dermatol 1999 Sep;26(9):595-8 Abstract quote
Infantile myofibromatosis is an unusual condition generally presenting in the newborn period.
The case being reported is that of a female newborn who had multiple lesions that involved skin, subcutaneous tissue, skeletal muscles, bone, and lungs. The disease was diagnosed because of the easily palpable skin tumors and subcutaneous nodules that were obvious immediately after birth. The diagnosis was established by histopathological examination of one nodule that showed a spindle-celled mesenchymatogenic lesion demonstrating the morphological and immuno-phenotype characteristics of myofibroblastic differentiation.
The histologic picture, combined with the clinical manifestations and the imaging findings, are consistent with infantile myofibromatosis. The physical condition of the newborn was excellent and remains so six months later. The tumors of the skin and the subcutaneous nodules have gradually regressed without therapy. At the age of six months, four (4) nodules are palpable; the infant is under continuous observation.
Dermatological presentations of infantile myofibromatosis: a review of 27 cases.
Stanford D, Rogers M.
Department of Dermatology, Royal Alexandra Hospital for Children, Sydney, New South Wales, Australia.
Australas J Dermatol 2000 Aug;41(3):156-61 Abstract quote
Twenty-seven cases of infantile myofibromatosis presenting with dermatological manifestations were retrospectively reviewed.
Approximately 80% were solitary lesions and 50% of these appeared on the head and neck. Around 60% were present at or soon after birth. Most lesions were dermal or subcutaneous, although some were intramuscular and intraosseous. The clinical appearance was non-specific leading to frequent misdiagnosis.
While most patients presented with nodules, atrophic depressed lesions and warty pedunculated lesions were also seen. Although 7% of lesions recurred after excision, spontaneous resolution was also documented.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL
Myofibromatosis in adults, glomangiopericytoma, and myopericytoma: a spectrum of tumors showing perivascular myoid differentiation.
Granter SR, Badizadegan K, Fletcher CD.
Department of Pathology, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Am J Surg Pathol 1998 May;22(5):513-25 Abstract quote
The clinicopathologic features of 24 tumors showing perivascular myoid differentiation are described. These included tumors with histologic features of "infantile-type" myofibromatosis occurring in adult patients (8 cases), tumors with composite features of "hemangiopericytoma" and glomus tumor (9 cases), and tumors with a distinctive concentric perivascular proliferation of spindle cells (7 cases).
Evidence of morphologic overlap among these groups suggests they are closely related neoplasms that form a single spectrum. Age of patients with lesions resembling infantile-type myofibromatosis ranged from 23 to 67 years (median, 37 years).
Clinicopathologic manifestations of this disease included multicentricity (4 cases), local recurrence (3 cases), persistence of congenital lesions into adulthood (4 cases), and tumors that were multifocal within the confines of one anatomic region (7 cases). Histologically, all cases showed a biphasic pattern that consisted of fascicles of spindle cells with abundant eosinophilic cytoplasm that resembled smooth muscle, in addition to a population of more primitive spindled cells associated with a hemangiopericytomalike vascular pattern. Six cases showed reversal of the typical zonation seen in pediatric cases in that the primitive component surrounded the more mature fascicular areas. Also described are nine tumors with features that are intermediate between glomus tumor and hemangiopericytoma, which we have designated glomangiopericytoma.
These tumors are characterized by prominent branching vessels lined by a single row of endothelial cells surrounded by epithelioid cells with a glomoid appearance. In other areas, the tumors showed typical hemangiopericytomatous foci similar to those in the myofibromatosis cases. The principal points of distinction were a lack of myoid nodules and an absence of small primitive cells with basophilic cytoplasm. Ages of these patients ranged from 17 to 78 years (median, 35 years). All tumors were located in the subcutaneous tissue and the superficial soft tissue of the extremities. Recurrence developed in one of six patients with follow-up information. The recurrent tumor had features of angiomatoid malignant fibrous histiocytoma.
Finally, we describe a subset of tumors characterized by concentric periluminal proliferation of bland, round to ovoid cells, which we have designated as myopericytoma. Patient age ranged from 10 to 66 years (median, 40 years). All were located in subcutaneous and superficial soft tissue of distal extremities. One patient had two recurrences in 3 years after initial excision.
Our study suggests that these three lesional groups comprise a histologic continuum of tumors that share clinical similarities and that, perhaps, are designated more appropriately as perivascular myomas. The relationship of this family of tumors to so-called hemangiopericytoma is discussed.
Solitary form of infantile myofibromatosis: a histologic, immunohistochemical, and electronmicroscopic study of a regressing tumor over a 20-month period.
Iijima S, Suzuki R, Otsuka F.
Department of Dermatology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
Am J Dermatopathol 1999 Aug;21(4):375-80 Abstract quote
We present the repeated clinical, histologic, immunohistochemical, and ultrastructural observations on a cutaneous myofibromatous tumor over a 20-month period. A 6-day-old Japanese female had a solitary tumor on her left wrist at birth. A biopsy was first performed at 16 days of age, when the tumor was likely fully developed. Thereafter, the tumor gradually regressed. A second biopsy was performed at 58 days of age, when the tumor was already in a phase of early regression. Finally, the tumor was resected at 20 months of age, when it was in a phase of late regression.
Our study demonstrated that undifferentiated immature histiocytic cells predominated over spindle cells in the first biopsy specimen, but thereafter the former cells decreased or disappeared in parallel with the increase in the latter cells, which showed characteristics similar to myofibroblasts, in regressing lesions.
This evidence suggests that the undifferentiated immature histiocytic cells are precursors of the spindle cells. Spindle cells in the phase of early regression also showed many vacuoles and lipid-like droplets in the cytoplasm, even though they actively produced massive amounts of glycogen. These findings also suggest that tumor regression results from cytoplasmic vacuolation and disruption of spindle cells.
Our results are considered to demonstrate, for the first time, the clinical and histologic features of the different developmental or regressive phases of infantile myofibromatosis.
Monophasic cellular variant of infantile myofibromatosis. An unusual histopathologic pattern in two siblings.
Zelger BW, Calonje E, Sepp N, Fink FM, Zelger BG, Schmid KW.
Department of Dermatology, University of Innsbruck, Austria.
Am J Dermatopathol 1995 Apr;17(2):131-8 Abstract quote
Infantile myofibromatosis (IMF) is a distinct clinicopathologic entity characterized by solitary or multicentric tumors present at birth or in early infancy with a typical biphasic (central hemangiopericytoma-like, peripheral leiomyoma-like) histologic pattern.
We present a case of IMF in two siblings with onset of disease in late childhood. Histology of the primary as well as several later tumors was characterized by a monophasic cellular appearance with a prominence of tiny capillaries initially suggesting an unusual vascular tumor. Diagnosis was established by the development of more characteristic biphasic lesions during the course of disease. Immunocytochemistry (Ulex, factor VIII, JC/70A [CD31], PAL-E, BMA120, EN4, QBEnd10 [CD34], SMS actin) and ultrastructural studies showed no (marked) differences between different types of IMF.
The monophasic cellular pattern should be recognized as an unusual histologic manifestation of IMF, in particular in patients outside the classical setting or presentation.
CHARACTERIZATION SPECIAL STAINS IMMUNOPEROXIDASE S-100 and smooth muscle actin positive
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES INFANTILE HEMANGIOPERICYTOMA
Infantile hemangiopericytoma versus infantile myofibromatosis. Study of a series suggesting a continuous spectrum of infantile myofibroblastic lesions.
Mentzel T, Calonje E, Nascimento AG, Fletcher CD.
Department of Histopathology, St. Thomas's Hospital, London, U.K.
Am J Surg Pathol 1994 Sep;18(9):922-30 Abstract quote
The clinicopathologic features of 11 tumors, originally diagnosed as infantile hemangiopericytomas and with a spectrum of morphologic findings, are described. The age of the patients ranged from 6 days to 7 years; seven patients were younger than 1 year (mean, 2.25 years; median, 10 months); six were boys and five were girls. Three neoplasms were situated in skin or subcutis and seven in deep soft tissue; in one case the depth was unstated. Seven lesions arose in the lower limbs, and one each in the lumbar region, clitoris, chest wall, and soft tissue of the zygomatic region. One patient later was found to have two additional dermal tumors, one each on the anterior abdominal wall and the chest wall. Follow-up information in eight patients revealed local recurrence 12 years later in one case only.
Histologically, all tumors showed distinctive features of infantile hemangiopericytoma, including immature cytology, multilobulated growth pattern, focal necrosis, and mitotic activity in varying degrees. Vascular invasion was noted in seven cases. Additionally, a second tumor cell component, composed of spindle-shaped myofibroblastic cells forming fascicles and micronodules, was evident at least focally. Both the spindle cells and more primitive round cells were positive for alpha-smooth muscle actin. Both cellular components showed a haphazard zoning arrangement.
We discuss the clinicopathologic similarities between infantile hemangiopericytoma and infantile myofibromatosis and point out the differences between infantile and adult hemangiopericytoma. Our study suggests that there exists a broad spectrum of benign infantile myofibroblastic lesions containing an immature-appearing cellular component with a distinctive, hemangiopericytoma-like vascular pattern. Infantile myofibromatosis and so-called infantile hemangiopericytoma almost certainly represent different stages of maturation of the same (single) entity.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSTIC FACTORS
Infantile myofibromatosis: the most common fibrous tumor of infancy.
Wiswell TE, Davis J, Cunningham BE, Solenberger R, Thomas PJ.
Department of Pediatrics, Brooke Army Medical Center, Ft Sam Houston, TX 78234-6200.
J Pediatr Surg 1988 Apr;23(4):315-8 Abstract quote
We describe the clinical courses of four infants with infantile myofibromatosis (IM). This entity is a mesenchymal disorder of early infancy characterized by the formation of tumors in skin, muscle, viscera, bone, and subcutaneous tissues. Previously known as congenital generalized fibromatosis, IM was formerly thought to be a rare condition that was frequently fatal. The majority of the 170 affected patients we describe have been diagnosed since 1980. Furthermore, the mortality rate for these patients is less than 15%.
Our review includes the clinical manifestations, as well as histopathologic features, and discusses the prognosis in affected infants. We found that infants with solitary lesions or multiple lesions without visceral involvement generally have a benign course. However, in patients with the multicentric form of the disorder and visceral involvement, 73% have died. Because the lesions may not be easily discernible and most spontaneously resolve, the condition is underdiagnosed and underreported.
IM is the most common fibrous tumor of infancy and must be considered when evaluating children who present with either solitary or multiple tumors, particularly during the neonatal period.
Generalized infantile myofibromatosis in a patient with Turner's syndrome: a trial of interferon-alpha.
Savasan S, Fulgenzi LA, Rabah R, Mohamed AN, Ravindranath Y.
Barbara Ann Karmanos Cancer Institute, Detroit, Michigan, USA.
J Pediatr 1998 Nov;133(5):694-6 Abstract quote
A patient with Turner's syndrome was found to have generalized infantile myofibromatosis with visceral involvement at birth. The infant was treated with interferon-alpha because of the size of the lesions.
Two months after treatment, the lesions appeared to have decreased in size and showed evidence of maturation with decreased apoptosis on histologic examination. Interferon-alpha treatment might induce regression of myofibromatosis.
Congenital hemangiopericytoma/infantile myofibromatosis: radical surgery versus a conservative "wait and see" approach.
Toren A, Perlman M, Polak-Charcon S, Avigad I, Katz M, Kuint Y, Rechavi G.
Pediatric Hemato/Oncology Department, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
Pediatr Hematol Oncol 1997 Jul-Aug;14(4):387-93 Abstract quote
Infantile/congenital hemangiopericytoma, although sharing many similar histological features with adult hemangiopericytoma, has a much better prognosis. Nevertheless, most cases described in the literature were pursued by radical surgery with or without adjuvant chemotherapy.
We describe a neonate who presented with a huge mass in the right gluteus, 6 x 5 x 4 cm, and a small ventral abdominal mass. The masses were confirmed on biopsy according to light microscopy, immunohistochemistry, and electron microscopy as congenital hemangiopericytoma. They shrank spontaneously within 2 weeks and vanished within 2 months.
We present a hypothesis that masses appearing in the neonatal period with this histology and with no life-endangering pressure on vital organs should routinely be dealt with conservatively.
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Soft Tissue Tumors
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