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It may come as a surprise to some of you but bone is continually growing and remodelling.  The bone forming cells including osteoblasts, osteocytes, and osteoprogenitor cells all actively synthesize bone matrix.   Meanwhile, the osteoclast is involved in resorption, dissolving the bone matrix proteins and breaking it down.  This balance of growth and resorption termed modeling and remodeling is tightly controlled by the body's parthyroid homrone and other cytokines. Bone and joint tumors are covered in a separate section.

Bone and Joint Tumors

Degenerative Joint Disease (Osteoarthritis)
Paget's Disease of the Bone (Osteitis Deformans)
Phosphaturic Mesenchymal Tumor (Oncogenic Osteomalacia)
Pigmented Villonodular Synovitis

Pseudogout (Calcium Pyrophosphate Crystal Deposition Disease)
Rheumatoid Arthritis
Still's Disease (Juvenile Rheumatoid Arthritis)
Synovial Chondromatosis


Disease Associations  
Gross Appearance and Clinical Variants  
Histopathological Features and Variants  
Commonly Used Terms  
Internet Links  

Latent Epstein-Barr virus (EBV) infection and cytomegalovirus (CMV) infection in synovial tissue of autoimmune chronic arthritis determined by RNA- and DNA-in situ hybridization.

Mehraein Y, Lennerz C, Ehlhardt S, Remberger K, Ojak A, Zang KD.

Department of Human Genetics, Saarland University, University Hospital, Homburg/Saar, Germany.
Mod Pathol. 2004 Jul;17(7):781-9. Abstract quote

In rheumatoid arthritis (RA) viral triggers, especially Epstein-Barr virus (EBV) and cytomegalovirus (CMV), have been suggested. By PCR analysis DNA of several viruses among which EBV, CMV, and parvovirus B19 (B19) has been detected in RA synovial fluid and synovial tissue. In 63 synovial tissues of 29 rheumatoid arthritis (RA), 6 psoriatic arthritis (PsA), 26 reactive arthritis/synovitis (rA/S), and two normal synovial cases, we recently could demonstrate a high percentage of replicative B19 infection within the synovial tissue, being significantly more frequent in autoimmune arthritis.

To further investigate the influence of synovial virus infections in rheumatoid arthritis, we now analyzed the same sample of synovial tissues for CMV and EBV infections by DNA-in situ hybridization (CMV), EBER1/2-RNA-in situ hybridization (EBV), and immunohistochemistry. A significant latent EBV infection of synovial lining cells, synovial fibroblasts, and/or infiltrating lymphocytes was identified in 5/29 (17.2 %) RA, 1/6 (16.7%) PsA, and to a much lower degree in 1/26 (3.8%) rA/S specimens. CMV-DNA was detected in 31% of RA, 3/6 (50%) of PsA, and 11.5% of rA/S.

Immunohistochemical analysis of CMV early antigen revealed replicative CMV activity in 20.7% of RA and 2/6 (33.3%) of PsA specimens but not in reactive arthritis synovia. Comparative analysis of the EBV-, CMV-, and published B19-data demonstrated that relevant synovial virus infections in general and furthermore double or multiple infections are far more common in autoimmune arthritis than in rA/S. A triple virus infection was found solely in RA in 10.3% of cases.

The evidence of increased synovial persistence of EBV, CMV, or B19 either alone or even more as coinciding infections may further reinforce the notion of a primary role of these viruses in autoimmune arthritis.

Incidence of cancer among patients with knee implants in Sweden, 1980-1994.

Fryzek JP, Ye W, Signorello LB, Lipworth L, Blot WJ, McLaughlin JK, Nyren O.

International Epidemiology Institute, Rockville, Maryland 20850, USA.

Cancer 2002 Jun 1;94(11):3057-62 Abstract quote

BACKGROUND: As knee implants become more common, it is important to study their potential health risks. We investigated cancer occurrence in a nationwide population-based cohort of 30,011 patients who underwent knee replacement surgery in Sweden from 1980 to 1994.

METHODS: Patients were followed from 1 year after the date of their surgery through December 31, 1995, accruing 122,616 person-years of observation. The average follow-up time was 4.3 years, with 2365 patients followed for 10 years or more.

RESULTS: Overall cancer incidence was not elevated compared with the general population of Sweden (standardized incidence ratio [SIR] = 1.03; 95% confidence interval [CI] = 0.98-1.08). A reduced rate for all respiratory cancers (SIR = 0.73; 95% CI = 0.59-0.91) and for lung cancer (SIR = 0.73; 95% CI = 0.58-0.91) was found among both men and women. Elevated rates were found for prostate (SIR = 1.20; 95% CI = 1.06-1.34) and bone cancer (SIR = 6.00; 95% CI = 1.24-17.52) in men. The bone cancer excess was based on three observed cases, two of which occurred at a site unrelated to the implant and the site of the third tumor is unknown. Rates of connective tissue cancer and leukemia-lymphoma were not elevated significantly among knee implant recipients. Long-term follow-up (>or= 10 years) did not show a significant excess risk for all cancer (SIR = 1.10; 95% CI = 0.86-1.38) or for any site-specific cancer, including bone cancer, lymphoma, or leukemia. Subgroup analyses for patients with rheumatoid arthritis produced results similar to the overall results.

CONCLUSIONS: This epidemiologic study of cancer risk among patients with knee implants is the largest to date. It provides evidence that the incidence of cancer among patients with knee implants is similar to that of the general population. Continued follow-up of this cohort is warranted to evaluate further potential long-term effects of these implants.



Sinus histiocytosis of pelvic lymph nodes after hip replacement. A histiocytic proliferation induced by cobalt-chromium and titanium.

Albores-Saavedra J, Vuitch F, Delgado R, Wiley E, Hagler H.

Department of Pathology, University of Texas Southwestern Medical Center, Texas, Dallas 75235-9072.

Am J Surg Pathol 1994 Jan;18(1):83-90 Abstract quote

Six men who had undergone hip replacements for degenerative joint disease or trauma subsequently had radical prostatectomies or cystoprostatectomies with bilateral pelvic lymph node dissections for adenocarcinoma of the prostate or transitional cell carcinoma of the urinary bladder.

The hip prostheses implanted in three patients were known to contain cobalt-chromium alloy and titanium. The pelvic lymph nodes ipsilateral to the hip prosthesis in five patients and the bilateral pelvic nodes in the only patient with bilateral hip prosthesis had dark brown or black cut surfaces. These lymph nodes did not contain carcinoma but showed florid sinus histiocytosis characterized by large polygonal histiocytes filling and expanding sinuses and interfollicular regions. The foamy histiocytes contained cobalt-chromium and titanium microparticles by light microscopy, ultrastructure, and energy-dispersive x-ray microanalysis. The lymph nodes uninvolved by the histiocytic reaction lacked the heavy metal microparticles. Four cases were found to have a small number of polyethylene particles, which might have contributed to the histiocytic response. By immunohistochemistry, the foamy cells displayed immunoreactivity for lysozyme, alpha-1-antitrypsin, alpha-1-antichymotrypsin, and cathepsin D, providing additional support for their histiocytic derivation.

To our knowledge, this is the first time that microparticles of cobalt-chromium and titanium that migrate from hip prostheses to pelvic lymph nodes have been shown to elicit a distinctive type of florid sinus histiocytosis. Pathologists should be aware of this characteristic foreign-body tissue response to avoid confusion with other types of sinus histiocytosis or with metastatic carcinoma.

An overview of the histology of skeletal substitute materials.

Department of Pathology, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44106, USA.

Arch Pathol Lab Med. 2007 Feb;131(2):217-24. Abstract quote

CONTEXT: Orthopedic and spine surgeons are in frequent need of bone for skeletal reconstruction. The amount of autograft is limited, and conventional allograft has some disadvantages, so surgeons are now using increasing amounts of demineralized allograft and a variety of synthetic materials to replace or "extend" autograft.

OBJECTIVE: To provide an overview of the composition and histology of the materials most likely to be seen by pathologists today.

DATA SOURCES: The review is based on published literature and the author's experience with preclinical studies and human biopsies.

CONCLUSIONS: Pathologists are likely to find these skeletal substitute materials in biopsy and resection specimens from patients who have undergone prior treatment, and recognizing a synthetic bone substitute can help explain an otherwise confusing specimen. Pathologists also play an important role in helping define the safety and efficacy of new bioactive materials.

Synovial metaplasia, a specialized form of repair.

Fowler MR, Nathan CA, Abreo F.

Departments of Pathology (Drs Fowler and Abreo) and Otolaryngology (Dr Nathan), Louisiana State University Health Sciences Center, Shreveport.

Arch Pathol Lab Med 2002 Jun;126(6):727-30 Abstract quote

Synovial metaplasia is a change seen most frequently in the tissues surrounding silicone breast prostheses and in healing tissue adjacent to joint prostheses. It has also been described in skin and soft tissues, most frequently in healing or healed traumatic or surgical wounds.

We report a case of synovial metaplasia occurring in a hitherto unreported location, namely, adjacent to a silicone low-pressure voice prosthesis. A review of cases of synovial metaplasia reported in the literature revealed that in most cases, spaces that form adjacent to foreign material (most commonly silicone breast prostheses) and the smooth gliding surfaces of the foreign material that resist penetration by fibroblast processes are frequent associated findings that precede the occurrence of synovial metaplasia.

Thus, synovial metaplasia might represent a specialized form of healing in cases that have this combination of physical features.


Tenosynovial (extraarticular) chondromatosis: an analysis of 37 cases of an underrecognized clinicopathologic entity with a strong predilection for the hands and feet and a high local recurrence rate.

Fetsch JF, Vinh TN, Remotti F, Walker EA, Murphey MD, Sweet DE.

Department of Soft Tissue, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA.

Am J Surg Pathol. 2003 Sep;27(9):1260-8. Abstract quote  

Tenosynovial chondromatosis is a multinodular cartilaginous proliferation that arises from the tenosynovial membranes.

This report describes the clinical, radiologic, and histopathologic findings in 37 cases of this uncommon entity. There were 17 males and 20 females, ranging in age from 20 to 86 years (mean and median age, 46 years). The process involved tenosynovium of the fingers (n = 19), feet (n = 8), wrists (n = 4), ankles (n = 2), hand, not otherwise specified, or palm (n = 2), knee (n = 1), and forearm (n = 1). Signs of disease or symptoms were present for 5 weeks to 18 years (median duration, approximately 2 years) before surgical excision. The two most common complaints were a painless mass and a mass that was mildly tender with pressure. None of the tumors had clinical, radiologic, or histopathologic evidence of articular or bone involvement. Histologically, all tumors consisted of a multinodular cartilaginous proliferation involving tenosynovium and/or subsynovial connective tissue. Mild or moderate atypia, as encountered in chondroma of soft parts and synovial chondromatosis, was a frequent finding.

Follow-up information was available for 16 patients (43%). Only two patients with follow-up information remained disease free after their initial surgical procedure. Seven patients had one recurrence and seven patients had two or more recurrences. Tenosynovial chondromatosis appears to be an extraarticular counterpart of synovial (intraarticular) chondromatosis.

Our review indicates this process is often confused with chondroma of soft parts, in part, because both entities have a predilection for the hands and feet. Diagnosis of this underrecognized entity is of clinical importance because of the high local recurrence rate.

Macpherson and Pincus. Clinical Diagnosis and Management by Laboratory Methods. Twentyfirst Edition. WB Saunders. 2006.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

Commonly Used Terms With Diseases of the Bones and Joints

Haversian Systems-These are vascular channels around which lamellar bone is deposited.

Lamellar Bone-This type of bone replaces woven bone and is deposited in a slower fashion in a layered orderly fashion.  It is much stronger than woven bone.

Woven Bone-This refers to the pattern which collagen which is synthesized by the osteoblasts and deposited in a random pattern.  

Basic Principles of Disease
Learn the basic disease classifications of cancers, infections, and inflammation

Commonly Used Terms
This is a glossary of terms often found in a pathology report.

Diagnostic Process
Learn how a pathologist makes a diagnosis using a microscope

Surgical Pathology Report
Examine an actual biopsy report to understand what each section means

Special Stains
Understand the tools the pathologist utilizes to aid in the diagnosis

How Accurate is My Report?
Pathologists actively oversee every area of the laboratory to ensure your report is accurate

Got Path?
Recent teaching cases and lectures presented in conferences

Internet Links

Last Updated February 19, 2007

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