A Multiple Myeloma of the Late Middle Ages from Unterregenbach, Southwestern Germany
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1 International Journal of Osteoarcbaeology, Vol. 5: (1 995) A Multiple Myeloma of the Late Middle Ages from Unterregenbach, Southwestern Germany MIRIAM NOEL HAIDLE lnstitut fur Ur- und Fruhgeschichte, Abteilung Altere Urgeschichte und Quartarokologie der Universitat Zbingen, Schloss, D Ebingen, Germany ABSTRACT In the early 1960s the grave of a probable donor was discovered in the St Veit church in Unterregenbach, Stadt Langenburg, Kreis Crailsheim, southwestern Germany. After a reexamination, the skeleton may be regarded as clearly corresponding to the typical ciinical picture of a multiple myelomdplasrna cell myeloma. The year-old female individual shows all the characteristics of a malignant plasma cell tumour, with specific osteolytic lesions of the skull, vertebrae, ribs, pelvis, scapulae and long bones, and even-sized single defects without reactive zones on the edges. Several pathological fractures of the ribs and a vertebral compression fracture can be observed. The gnawing-mark-like features on the inner surface of the compact bone and the 'punched-out' lesions on the outer are distinguishing marks of a multiple myeloma. Keywords: multiple myeloma; malignant tumour; systemic disease; Late Middle Ages. Introduction In the early 1960s, when studies on palaeopathology were not so common as they are nowadays, the skeleton of a mature female individual was excavated in the St Veit church in Unterregenbach, Stadt Langenburg, Kreis Crailsheim, southwestern Germany. The bones were examined like the other skeletal remains from the church and the churchyard, without recognizing the pathological lesions on every single bone of the individual. The skeletons were stored as a series in the Osteological Collection of the University of Tubingen. Only by chance were the bone fragments of the female individual with severe pathological changes rediscovered. The remains consist of a rather complete skull with the maxilla, a fragmentary mandible, parts of both humeri, both radii and ulnae, both femora, carpal and metacarpal bones and phalanges of the right and left hand. Numerous fragments of vertebrae and ribs, parts of both scapulae and the pelvis, as well as the distal part of the sacrum can be determined. The 0s coccyx is preserved as a whole. The individual is documented in the ccc x/95/ by John Wiley & Sons, Ltd. inventory of the Osteological Collection of the University of Tubingen under the numbers 4383 and The skeleton belongs to a woman of years of age. The body height of 162cm is estimated on the basis of the parallel length of the refitted right radius of 233 mm.' The individual was buried in the church as one of three in this particular phase, and lay in front of the central altar,. this may imply the grave of a donor. The burial belongs to the second building phase of the St Veit church (I1 ib 2) and dates, therefore, to the thirteenth to the fifteenth centuries AD.^ Materials H. Preuschoft and H. Schneider examined the skeletal remains from Unterregenbach but did not recognize the severe osteolytic processes manifested on the skeleton of the female individual, in their pathological significance (Figure 1). They describe the skull as thickened and spongyly increased. 'The upper jaw and the nasal area don't show these changes, but the Received 3 1 December 1994 Accepted 25 April 1 995
2 3 60 M. N. Haidle Figure 1. A selection of bone fragments from the Unterregenbach individual with numerous pathological features. mandible is severely affected. The other bones the density of the trabecular bone is markedly show the same severe osteoporosis as well. It is lowered. The lamina externa shows 'punched-out' not restricted to the cancellous bone but has also lesions: especially the pars squamosa of both thinned the cortical part of the long tubular bones temporal bones, but also the parietal, the frontal considerably.'3 and the occipital are characterized by The skull of the individual is, as described by perforations on the outer surface (Figure 2a and Preuschoft and Schneider, slightly thickened and b). The diameter of the lesions extend from 1 mm Figure 2a. (caption opposite).
3 Multiple Myeloma 361 Figure 2. (ax) The skull of the Unterregenbach individual. Note the numerous punched-out lesions and the even size of the single defects. to a maximum of 4mm. In the area of the sutura sagitalis, a defect several centimetres large is located that developed post-mortem. The lamina interna is only slightly perforated but has a large spaced osteolytic destruction in the area of both parietal bones (Figure 2c). X-rays of the skull, however, show no different picture in this area: the destruction of the lamina interna probably represents a post-mortem phenomenon (Figure 3a-c). The facial bones are not affected and the maxilla only slightly. The mandible, however, shows numerous defects (Figure 4) on both sides of the corpus mandibulae both laterally and medially. The trabecular structures are dissolved to a large extent (Figure 5). The postcranial part of the skeleton is severely affected by the disease. The vertebral column shows marked osteolytic destruction; at least one corpus vertebrae with a compression fracture (Figure 6) is preserved. The processuus spinosi of
4 362 M. N. Huidle Figure 3a-b. (caption opposite).
5 Multiple Myeloma 363 Figure 3. (a-c) X-ray pictures of the skull showing the entire skull vault systemically affected. the vertebrae, as well as every preserved rib sacrum, the coccyx and the scapulae are fragment, are studded with small perforations. perforated. Several of the pathologically frail ribs broke The extremities show more differentiated during the course of the disease: the callus of the changes. The caput of both humeri and femora healing process can be observed on several have numerous perforations, as well as the fragments (Figure 7). The fragments of the diaphyses of the humeri. On a shaft fragment of pelvic are affected by osteolytic lesions, the the left humerus, gnawing-mark-like osteolytic Figure 4. The mandible of the Unterregenbach individual. The corpus mandibulae manifests a large number of osteolytic lesions. The large defect on the right is not a pathological lesion, there the bone is broken down post-mottem.
6 364 M. N. Haidle Figure 5. X-ray picture of the mandible. The trabecular structures are dissolved to a great extent. traces are present on the inner surface (Figure 8). Here, the cortical bone was destroyed from the marrow cavity. The breakthrough of these processes leads to the numerous perforations on the outer surface of the tubular bones. On the distal joint of the left humerus, globular defects can be observed with a diameter of barely 1 cm, which in part pass into one another (Figure 9). The cancellous bone is in this area completely Figure 6. Corpus vertebrae with compression fracture. dissolved. Both radii and ulnae show perforations on the cortex that appear more frequently at the proximal end and decrease in number towards the distal epiphyses. On the preserved short bones of the hands, no changes could be observed. Discussion and interpretation The described defects on the skull of the female individual from Unterregenbach are exemplary for the pathological changes of the bone tissue due to a multiple myeloma. The multiple myeloma, also known as plasma cell myeloma and plasmocytoma, is the most frequent primary malignant tumour that manifests on bones. It originates in a neoplastic proliferation of the plasma cells of the bone marrow, in most cases it appears as a systemic di~ease.~ This plasma cell tumour occurs mainly during the sixth and the seventh decades of life and affects men more frequently than women. The disease starts in the hematopoietic marrow and may lead in the end to a destruction of the compact bone. An osseous distinguishing character is the 'small shot skull', with sharply limited, 'punched-out'-like osteolytic foci without sclerosis on the edges. The cortical bone often looks as if it has gnawing marks. The osteolytic lesions are round or oval in general and do not exceed a 1Omm diameter. Vertebrae, ribs, the
7 Multiple Myeloma 365 Figure 7. Rib fragments with osteolytic lesions showing fractures and callus of the healing process. sternum, claviculae, scapulae, the pelvis, the skull in the collapse of the corpus vertebrae, a and the long bones are most frequently affected by spontaneous compression fracture. Ribs often the pathological processes. The facial bones and the short bones of the hands and feet are usually not show pathological fractures.6 As a differential diagnosis, the possibility of involved. The destruction of the trabecular osteolytic metastasis of a carcinoma has to be structures of the vertebral column may culminate taken into account. What argues against this Figure 8. Shaft fragment of the left humerus. Note the gnawing-mark-like osteolytic traces on the inner surface.
8 366 M. N. Huidle Figure 9. Distal joint of the left humerus. Note the globular osteolytic defects which pass into one another. diagnosis in this case are the sharply limited destructions of the trabecular structures without detectable sclerosis at the edges. These are due to plasma cell tumours with a diameter of up to 1 cm that replace the bone marrow.' Their negatives, that are preserved as a hollow body in the cancellous bone after the decay of the soft tissue, are clearly to be seen at the distal joint of the left humerus. The systemic dissemination of the lesions is characteristic for a multiple myeloma. An affection of radius and ulna is very uncommon for metastases of a carcinoma. Especially, the quite even size of the single defects is regarded as specific for a multiple myeloma.6 Multiple inflammatory processes have to be considered as another differential diagno~is.~ This possibility may, however, be excluded due to the multitude and characteristic attributes of the defects described above. The cases of a multiple myeloma listed so far in the literature6j are problematical for several reasons. Especially, the reactive zones that frequently can be observed at the edges of the osteolytic defects of the individuals make a diagnosis as metastasis of carcinoma more likely.g,'o Also, doubts on the diagnosis occurred due to the fact that most of the documented pre-columbian cases are less than 40 years old. It was argued that this difference represents an artefact that appears because of statistics based on studies of European and USA populations that are not comparable to other populations.8 A racial or geographical deviation of the age distribution cannot be determined in younger studies. it is very important in Ortner and Putschal-6 to point to the even size of the single lesions due to plasma cell myeloma, their description and photographs of the small and very numerous defects on the vertebral column and the ribs of a woman with multiple myeloma examined post-mortem correspond exactly to these of the female individual from Unterregenbach. Beside the widespread osteolytic bone destructions, hypercalcaemia is a common feature in multiple myeloma. In the course of the disease, renal malfunction may occur as well as lowered immune response, which causes an increased susceptibility to infections of all kinds, and increased setum viscosity. An initial symptom of this tumour is a weak pain mainly in the area of the pelvis, the spinal column and the thoracic
9 Multiple Myeloma cage, that may not have been explained by a preceding injury. Strain and activity intensib the diffuse bone pain. In an advanced phase of multiple myeloma the pain increases mostly due to frequent pathological fractures of the ribs and spontaneous vertebral compression fractures. A severe weight loss and anaemias occur in many cases. The main causes of death are infections and renal failure. The disease of the female individual from Unterregenbach is likely to have taken a rather fast course: in 1955, before the application of chemical treatment, 52 per cent of the patients with a multiple myeloma died within 3 months, and only about 3 per cent survived for 2 years after the diagnosis. Thus, the female individual from Unterregenbach shows all the characteristics of an affection with multiple myeloma, a malignant plasma cell tumour. On the basis of the specific distribution of the lesions on the skeleton, the quite even size of the single defects without reactive zones on the edges, numerous pathological fractures of the ribs, a vertebral compression fracture, the gnawing-marklike features on the inner surface of the compact bone and the punched-outf lesions on the outer surfaces of the bones, the skeleton may be regarded as clearly corresponding to the typical clinical picture of a multiple myelomdplasma cell myeloma. Acknowledgements I want to thank Dr A. Czarnetzki, the head of the Osteological Collection of the University of Tubingen. He gave me the permission and the encouragement to examine and publish details of this skeleton. References Bach, H. Zur Berrechnung der Korperhohe aus den langen Gliedmaflenknochen weiblicher Skelette. Antbropologiscber Anzeiger, 1965, 29: Fehring, G. P. Unterregenbach. Kirchen, Herrensitz, Siedlungsbereiche. Die Untersuchungen der Jahre , mit einem Vorbericht uber die Grabungen der Jahre Forschungen und Berichte der Archaologie des Mittelalters in Baden- Wiirttemberg 1. Stuttgart: Theiss, Preuschoft, H. and Schneider, H. Die Skelettreste aus der Grabung St. Veit. In: Unterregenbach. Kirchen, Herrensitz, Siedlungsbereiche (edited by C. P. Fehring). Stuttgart: Theiss, 1972: Spjut, H. J., Dorfman, H. D., Fechner, R. E. and Ackerman, L. V. Tumors of Bone and Cartilage. Washington: Armed Forces Institute of Pathology, Adler, C.-P. Knochenkrankheiten. Stuttgart, New York: Thieme, Ortner, D. J. and Putschar, W. G. J. Identification of Pathological Conditions in Human Skeletal Remains. Washington, London: Smithsonian Contributions to Anthropology 28, 1981: Huvos, A. G. Bone Tumors. Diagnosis, Treatment, and Prognosis, 2nd edn. Philadelphia: W. B. Saunders, 199 I. 8. Morse, D., Dailey, R. C. and Bunn, J. Prehistoric Multiple Myeloma. Bulletin of the New York Academy of Medicine, 1974; 50: Steinbock, R. T. Paleopathological Diagnosis and Interpretation. Bone Diseases in Ancient Human Populations. Springfield, Illinois: C. C. Thomas, Brothwell, D. The Evidence of Neoplasms. In: Diseases in Antiquity (edited by D. Brothwell and A. T. Sandison). Springfield, Illinois: C. C. Thomas, 1967:
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