Bruce D. Ragsdale

Polymorphic fibro-osseous lesions of bone: an almost site-specific diagnostic problem of the proximal femur.

Atypical fibro-osseous lesions, usually in the proximal femur, are a common consultative diagnostic problem. This is due to the fact that they contain a variety of patterns individually reminiscent of fibrous dysplasia, fibroxanthoma (non-ossifying fibroma), myxofibroma, lipoma, cyst, bone infarct, Pagets disease, and, occasionally, chondroma. The variety of patterns in a single lesion precludes a simple designation. A diagnosis based on the predominant pattern would ignore this histologic complexity, which can be predicted by location in the proximal femur and a distinctive radiographic configuration. Personal experience with 95 heterogeneous lesions indicates they are usually incidental findings. They have a broad adult age range, but quite likely have their inception in childhood and slowly alter their appearance over a lifetime. In the majority of instances asymptomatic discovery, lack of distortion of bone outline, and sclerotic borders are indications of stability over many years. Other lesions gradually enlarge, predisposing to pathologic fracture. In parallel with some enchondromas and bone infarcts, a minority of lesions undergo malignant transformation.

Accuracy in Dry Bone Diagnosis: a Comment on Palaeopathological Methods

The objectives of palaeopathological research include: (i) diagnosis of specific diseases in archaeological human remains; (ii) analysis of the impact of various diseases in human populations through time and space; and (iii) clarification of evolutionary interactions between humans and disease. Basic to all these objectives is the need for accuracy in diagnosing diseases in archaeological human remains. Tests of diagnostic accuracy made during workshops in dry bone diagnosis held during the annual meetings of the Paleopathology Association (PPA) in 1989, 1990, 1991 and 1992 suggest important limitations that need to be considered in the development of methods in palaeopathology. Although the conditions do not approximate those found in most field or laboratory situations, these tests indicate an overall accuracy of 28.6 per cent for specific disease recognition and 42.9 per cent accuracy for correct recognition of the more general categories of disease. The factors in diagnostic accuracy are complex and include the knowledge and experience of the observer. Another factor is the often substantial morphological overlap between different diseases. In the classificatory system used for the workshops there are seven general categories of disease, each of which has recognizable, although often non-specific, hallmarks in dry bone specimens. A differential diagnosis with these seven general possibilities in mind rather than hundreds of specific diseases can be a powerful tool for the palaeopathologist in providing data that are more comparable between observers. This improvement in classificatory agreement has important methodological implications in the development of a data protocol in palaeopathological research. The identification of general disease category is recommended as part of descriptive and diagnostic reports on palaeopathological specimens.

Cutaneous metastasis of osteosarcoma in the scalp.

As a primary malignant bone tumor, osteosarcoma is second only to chondrosarcoma. Although it commonly metastasizes and is aggressive in nature, it rarely colonizes the skin. This is a report of a 22-year-old male with osteosarcoma of the pelvis and metastasis to the lungs and chest wall who developed a clinically unsuspected solitary cutaneous metastasis in the scalp. Instead of the expected cyst, incisional biopsy disclosed a solid tan nodule of chondro-osseous sarcoma. Although rare, cutaneous metastases from osteosarcoma may appear in skin, especially the scalp, or in skin over the primary tumor. New skin lesions in a patient with a history of osteosarcoma warrant investigations including imaging and biopsy.

Calcific Periarthritis: More Than a Shoulder Problem

BACKGROUND Calcific periarthritis, referring to a circumscribed juxta-articular deposit of minute non-birefringent mineral grains, is rarely the clinical diagnosis accompanying a pathologic specimen. Familiarity with the clinical, pathologic, and radiologic manifestations of calcific periarthritis, particularly when encountered adjacent to joints other than the shoulder, facilitates diagnosis and may obviate biopsy, avoid confusion with other entities, and speed appropriate treatment. METHODS Pathologic specimens that fulfilled the criteria for a diagnosis of calcific periarthritis were prospectively collected. Clinical history and radiologic studies were acquired and analyzed. Well-controlled special stains were employed on two specimens with a neutrophilic infiltrate that excluded fungal and bacterial agents, as corroborated by microbiologic cultures showing no growth. RESULTS Over a five-year period, fifteen patients between the ages of thirty-one and eighty-eight years (mean age, fifty-nine years) presented to various local healthcare providers for treatment of juxta-articular swelling that was subsequently determined to be calcific periarthritis. In seven patients, deposits were alongside a toe joint; in five, alongside a finger joint; and in three, involving the shoulder. The majority of the patients were female (73%). No patient had a documented recurrence of calcific periarthritis in follow-up periods ranging from eighteen to eighty-seven months (average forty-five months). CONCLUSIONS Of twelve histologically verified cases of calcific periarthritis adjacent to joints other than the shoulder, in only one patient (toe) was the preoperative clinical diagnosis accurate, which signals the need for greater awareness of this entity as a differential diagnostic option.

Large neglected ulcerated melanoma mimicking extramedullary plasmacytoma.

Amelanotic melanoma, a renowned impersonator, has taken on a new persona. A 63-year-old woman was seen in the emergency room with a chief complaint of back pain after a fall and was discovered to have a 15-cm fungating mottled gray mass independent of bone on the right elbow. Initial workup discovered lytic calvarial lesions, anemia (Hb 7; Hct 20%), and circulating plasma cells consistent with plasma cell myeloma. Biopsy of the elbow mass displayed sheets of plasmacytoid cells, some reactive for CD138. Flow cytometry revealed a substantial portion of the plasma cells in the tumor that were kappa restricted consistent with cutaneous plasmacytoma. The elbow mass was initially signed out as extramedullary involvement by her myeloma. Reevaluation of the mass after the patient experienced an explosive growth of multinodular jet black malignant melanoma on ipsilateral breast revealed MART-1 and S-100 reactivity of the majority of the cells. In retrospect, the elbow mass was a neglected primary amelanotic malignant melanoma with neoplastic plasma cells participating in its chronic inflammatory infiltrate.

Neoplasm or not? General principles of morphologic analysis of dry bone specimens

Unlike modern diagnosticians, a paleopathologist will likely have only skeletonized human remains without medical records, radiologic studies over time, microbiologic culture results, etc. Macroscopic and radiologic analyses are usually the most accessible diagnostic methods for the study of ancient skeletal remains. This paper recommends an organized approach to the study of dry bone specimens with reference to specimen radiographs. For circumscribed lesions, the distribution (solitary vs. multifocal), character of margins, details of periosteal reactions, and remnants of mineralized matrix should point to the mechanism(s) producing the bony changes. In turn, this allows selecting a likely category of disease (e.g. neoplastic) within which a differential diagnosis can be elaborated and from which a favored specific diagnosis can be chosen.

Mixed Pneumocystis and Cryptococcus cutaneous infection histologically mimicking xanthoma.

Cutaneous Pneumocystis jirovecii infection is rare. It is thought that the disease emerges from a latent infection delivered via hematogenous and/or lymphatic dissemination from a primary lung infection in immunocompromised individuals. A 32-year-old human immunodeficiency virus-positive male was admitted for headache and vomiting. He was diagnosed with meningitis due to Cryptococcus neoformans and sputum tested positive for Pneumocystis. Six months later, he presented with a slightly crusted yellowish brown plaque and 2 similar but smaller papules with telangiectasia near the right angle of the mouth. Biopsy of the area featured histiocytes expanded by foamy cytoplasm as in a xanthoma except that the vacuoles were coarser. Special stains ultimately demonstrated the characteristic disks of Pneumocystis accompanied by a minor component of budding yeasts (Cryptococcus) in the same fields. This case illustrates the utility of adequate special stains in recognizing a mixed cutaneous infection, particularly in human immunodeficiency virus-positive patients, when microscopy presents an odd xanthoma-like lesion.

Hyalin perivascular arcs and rings in sclerosing atypical fibroxanthomas.

To the Editors: Several variants of atypical fibroxanthoma (AFX) are split based on cytomorphology, for example, clear cell, granular cell, and spindle cell nonpleomorphic types. Nine cases of an unusual variant of AFX with keloidal tumoral sclerosis were presented by Kim and McNiff, following in from an anecdotal report and series of ‘‘keloidal’’ AFX. In several cases, ‘‘the keloidal collagen also formed ring-shaped structures surrounding CD31-positive vascular structures.’’ This report conveys our research on the perivascular sclerosis in a subset of 10 AFX examples with collagenous arcs and rings (Table 1). This curious arc and ring pattern of hyalinized collagen in some AFXs is morphologically similar to the always superficially located perivascular linear and tubular sclerosis in a minority of dermatofibromas. It is cautioned that the keloidal collagen associated with atypical fibrohistiocytic cells in AFX may erroneously lead to the diagnosis of ‘‘keloidal dermatofibroma.’’ Interesting in this regard, it has been said that the spectrum of fibrous histiocytoma (a diagnostic term utilized as a synonym for dermatofibroma) can be viewed somewhat more broadly, with dermatofibroma (DF) at one pole and with its ‘‘malignant analogue’’ AFX at the other. In both entities, AFX and DF, a sparse central component of CD31positive cells in the sclerotic arcs and rings deemed endothelial cells led to our initial hypothesis that the ‘‘keloidal collagen’’ is actually vascular basement membrane material of effete capillaries. Laminins, nidogens, and perlecans are arranged into highly organized supramolecular architectures by vascular basement membranes. We proposed the adherence of these elements likely explained the homogeneous (hyalinized) appearance of this material by obscuring its fibrillar texture (Figs. 1, 2). However, reactions for collagen type IV (specific for vascular basement membrane material) were negative for the morphologically similar curvilinear and circular material in both our AFX and DF examples. Also unreactive were the coarsehyalinizedcollagenbandsofacommon keloid, which like dermal collagen, are predominantly collagen type I. Pericytes are actin-positive cells situated in the basement membranes outside the endothelium of capillaries and venules. During the onset of angiogenesis the intramural pericytes leave the microvascular wall and enter the perivascular space, where they become collagen producing stromal cells. Sundberg et al identified 4 stages of pericyte migration/ progression from the endothelium to a collagen-synthesizing fibroblast in the interstitium. Pericytes have been identified in the wound-healing process via their expression of platelet-derived growth factor, a moiety which enhances neoformation of collagen and is associated with a collagen-rich dense tumor stroma, and have been shown to differentiate into collagenproducing cells during liver fibrosis. Double immunohistochemical reactions in our AFXs and DFs alike display concentric pattern: luminal CD31-positive endothelial cells within a ring of actinpositive pericytes that face the external rim of sclerotic material (Figs. 1C, 2B). Lesional cells of both DF and AFX show no consistent propensity to border the sclerotic material, discounting any role they might have in producing it. This leaves the pericyte stimulated to differentiate into fibroblasts when in a proliferative ‘‘fibrohistiocytic’’ environment, as the sole architect because it is consistently found within the rings as expected. Sclerotic hyalin rings similar to the material under discussion have been illustrated in hemangiopericytomas. The consistent localization of the pericyte to within the hyalin rings of the 10 sclerosing AFXs in this series supports the hypothesis that this material is synthesized by pericytes, a proposition that should be tested by more sophisticated studies.

Plastic bag clip discovered in partial colectomy accompanying proposal for phylogenic plastic bag clip classification

A plastic bag clip was incidentally found anchored in the mucosa of a partial colectomy specimen 2.6 cm proximal to a ruptured diverticulum for which the patient, a mentally retarded, diabetic, 58-year-old man, underwent surgery. Over 20 cases of accidental ingestion of plastic bag clips have been published. Known complications include small bowel perforation, obstruction, dysphagia, gastrointestinal bleeding and colonic impaction. Preoperative diagnosis of plastic clips lodged in the gastrointestinal tract is frustrated due to radiographic translucency. This occult threat could likely be prevented by the design of gastrointestinally safe, plastic-bag-sealing devices. Presented here is a morphologically based classification of bag clips as a possible guide for determining the most hazardous varieties and to aid further discussions of their impact on health.

Ischemic fasciitis: enhanced diagnostic resolution through clinical, histopathologic and radiologic correlation in 17 cases.

Ischemic fasciitis is a pseudosarcomatous nodule or mass resulting from sustained or repeated pressure and consequent ischemia of soft tissue. Fibrin and hemorrhage expand its hypocellular epicenter bordered by enlarged (atypical, ischemic) fibroblasts and reactive vascular prominence resulting in diagnostically important histologic zonation. Although classically in bedridden patients, ischemic fasciitis owing to posture‐related intermittent pressure in ambulatory adults is not well characterized; there has not been a thorough review of its presentation in ambulatory patients in the dermatology/dermatopathology literature. This article reviews the clinical, pathologic and radiologic presentation of 17 cases of ischemic fasciitis diagnosed over a 14‐year period. Eighty‐six percent of the six cases submitted by non‐dermatologists were limb girdle/trunk lesions averaging 6.7 cm in greatest diameter while 90% of the eleven lesions submitted by dermatologists were elbow and forearm lesions averaging 2.3 cm. In no case was the diagnosis anticipated pre‐biopsy by clinician or radiologist. Dermatologists submitted the majority of cases. Because ischemic fasciitis may simulate soft tissue sarcoma clinically and histologically, diagnosis helps prevent overtreatment. Zonal histopathologic structure may be shown by any form of biopsy and should motivate correlation with available radiologic studies. Importantly, determining a history of postural pressure at the site confirms the histopathologic diagnosis and avoids unnecessary excision.