Hyperostosis cranii ex vacuo: A rare complication of shunting for hydrocephalus

CASE STUDIES 4. Detection of neuronal mRNA of the rat pituitary pars intermedia with a digoxigenin-tailed oligonucleotide probe for proopiomelano-cortin (POMC), in Nonradioactive In Situ Hybridization: Application Manual. Mannheim, Germany, Boehringer Mannheim GmbH-Biochemica, 1992, pp 52-54 5. Ambinder RF, Lambe BC, Mann RB, et al: Oligonucleotides for PCR amplification and hybridization detection of EBV DNA in clinical specimens. Mel Cell Probes 4:397-407,1990 6. Trainer KJ, Brisco MJ, Story CJ, et al: Monoclonality in B lymphoproliferative disorders detected at the DNA level. Blood 75:222&2222,1990 7. Nalesnik MA, Jaffe R, Starzl TE, et al: The pathology of post-transplant lymphoproliferative disorders occurring in the setting of cyclosporin A-prednisane immunosuppression. Am J Path01 133:173192,1988 8. Canfield CW, Hudnall SD, Colonna JO, et al: Fulminant Epstein-Barr virus-associated post-transplant lymphoproliferative disorders following OKT-3 therapy. Clin Tramp1 61-9, 1992 9. Crierson H, Purtilo DT: Epstein-Barr virus infection in males with the X-linked lymphoproliferative syndrome. Ann Intern Med 106:538-545,1987 10. Israel AM, Koziner B, Straus DJ: Plasmacytoma and the acquired immonodeficiency syndrome. Ann Intern Med 99:635-636,1983 11. Vandermolen LA, Fehir KM, Rice L: Multiple myeloma in a homosexual man with chronic lymphadenopatby. Arch Intern Med 145:745-746,1985 12. Kamad A, Wright J: Neoplastic complications of human immunodeficiency virus infection. Am J Med 82:1282, 1987 (letter) 13. Voelkerding KV, Sandhaus LM, Kim HC, et al: Plasma cell malignancy in the acquired immune deficiency syndrome. Am J Clin Pathol 92:222-228, 1989 14. Obrams GI, GrufTemun S: Epidemiology of HIV associated non-Hodgkin lvmohoma. Cancer Sure 10:91-102.1991 i5.’ Penn I: Cancer in the immunbsuppressed organ recipient. Transplant Proc 23:1771-1772, 1991 16. Penn I: Multiple myeloma in a renal transplant recipient. Am J Kidney Dis 11:201, 1988 (letter) 17. Penn I: The changing pattern of post-transplant malignancies. Transplant Proc 23:1101-1103,199l 18. Strand WR, Banks PM, Kyle RA: Anaplastic plasma cell myeloma and immunoblastic lymphoma. Am J Med 76:861-867,1984 19. Grogan TM, Spier CM: The B cell immunoproliferative disorders, including multiple myeloma and amyloidosis, in Knowles DM (ed): Neoplastic Hematopathology. Baltimore, MD, Williams & Wilkins, 1992, pp 123.51265 20. Bartl R, Frisch B, Fateh-Moghadam A, et al: Histologic classification and staging of multiple myeloma. Am J Clin Pathol87:342-355, 1987 21. Purtilo DT, Strobach RS, Okano M, et al: Epstein-Barr virus-associated lymphoproliferative disorders. Lab Invest 67:523, 1992 22. Hanto DW, Frizzera G, Gajl-Paczalska KJ, et al: Epstein-Barr virus-induced B-cell lymphoma after renal transplantation. N Engl J Med 306:915918, 1982

HYPEROSTOSIS

CRANII

EX VACUO:

23. Ho M, Miller G, Atchinson RW, et al: Epstein-Barr virus infections and DNA hybridization studies in post-transplantation lymphoma and lymphoproliferative lesions: The role of primary infection. J Infect Dis 152:876886,1985 24. Bloom RE, Brennan JI& Sullivan JL: Lymphoma of host origin in a marrow transplant remission of acute myeloid leukemia and receiving cyclesporin A. Am J Hematol 18:73-83, 1985 25. Garcia CR, Brown NA, Schreck R, et al: B-cell lymphoma in a severe combined immunodeficiency not associated with the Epstein-Barr virus. Cancer 60:2941-2947, 1987 26. Knowles DM, Chadhurn A, Inghirami G: Immunophenotypic markers useful in the diagnosis and classification of hematopoietic neoplasms, in Knowles DM (ed): Neoplastic Hematopathology. Baltimore, MD, Williams & Wilkins, 1992, pp 91-93 27. Hummel M, Korbjuhn P, Anagnostopoulos I, et al: Detection of EBV DNA and gene products in a large series of B cell non-Hodgkin’s lymphoma. Fifth International Symposium on EBV, Annecy, France, September 1992 28. Starzl TE, Nalesnik MA, Porter KA, et al: Reversibility of lymphomas and lymphoproliferative lesions developing under cyclosporin-steroid therapy. Lancet 1:583-587,1984 29. Greipp PR, Raymond NM, Kyle RA, et al: Multiple myeloma: Significance of the plasmablastic subtype in morphological classification. Blood 65:305310,1985 30. Gatin AJ, Self S, Sabovic EA: The occurrence of a peripheral T-cell lymphoma in a chronically immunosuppressed renal transplant patient. Am J Surg Path01 12:6470,1988 31. Uhich W, Chott A, Wastchinger B, et al: Primary peripheral T-cell lymphoma in a kidney transplant under immunosuppression with cyclosporin A. HUM PATHOL20:1027-1030,1989 32. Griffith RC, Saha BK, Janney CM, et al: Immunoblastic lymphoma of Tie11 type in a chronically immunosuppressed renal transplant recipient. Am J Clin Path01 93:28&285,1990 33. Kemnitz J, Creme J, Gebel M, et al: T-cell lymphomas after heart transplantation. Clin Pathol94:95-101, 1990 34. Hacker SM, Knight BP, Lunde NM, et al: A primary central nervous system T-cell lymphoma in a renal transplant patient. Transplant 53:691692, 1992 35. Kumar S, Kumar D, Kingma DW, et al: Epstein-Barr virus-associated Tcell lymphoma in a renal transplant patient. Am J Surg Pathol 17:10461053, 1993 36. Kaplan MA, Jacobson JO, Ferry JA, et al: T-cell lymphoma of the vulva in a renal allograft recipient with associated hemophagocytosis. Am J Surg Path01 17:842-849,1993 37. Lippman SM, Grogan TM, Carry P, et al: Post-transplantation Tie11 lymphoblastic lymphoma. Am J Med 82:814816, 1987

A RARE COMPLICATION

OF SHUNTING

FOR HYDROCEPHALUS

JOHN A. DI PRETA, BS, JAMES M. POWERS, MD, AND DAVID G. HICKS, MD

Hyperostosis cranii ex vacua is a condition that may develop after successful ventricular shunting for hydrocephalus. It is characterized by diffuse thickening of the skull (particularly the inner table) involving the calvarium and the base. It is a diagnosis that distinguishes marked calvarial thickeningfrom thickening of the skull because of other causes. It is an entity that needs to be considered in patients who have diffuse thickening of the skull, have @mature closure of sutures, and who have been treated fm hydrocqbhalus in the past. HUM PATHOL 25:545-547. Copyright 0 1994 by W.B. Saunders Com-

Panr From the Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY. Accepted for publication February 8, 1994. Key mm%: hyperostosis cranii ex vacua, postshunting complication, hydrocephalus. Address correspondence and reprint requests to DavidG. Hicks,

MD, Department of Pathology, Box 626, University of Rochester School of Medicineand Dentistry,601 ElmwoodAve, Rochester, NY 14642. Copyright0 1994 by W.B. SaundersCompany 0046-8177/94/2505-0018$5.00/0

Hyperostosis cranii ex vacua is an entity that was described by Moseley et al’ as a marked thickening of the calvarium after shunting procedures for hydrocephalus. We report a case of this rare and delayed complication of shunting. CASE REPORT The patient was a 34year-old black woman who at 3 days of age had been noted to have obstructive hydrocephalus, for which she was treated with a ventriculoatrial or ventriculoperitoneal shunt. Developmentally the patient exhibited mild mental retardation but attended public schools as an adoles cent. At 28 years of age she had a prolonged seizure resulting in less ambulation, less cognition, and behavioral changes. In June of 1990 she fell down a flight of stairs and was admitted to a local hospital with a contusion to the cervical spinal cord and subsequent quadriplegia. She also had a history of recurrent fevers, hypotension, emesis, menorrhagia, and urinary tract infections. Her most recent admission to our hospital was for fever, nausea, emesis, and dizziness. A shunt tap was negative for bacteria and showed no evidence of increased intracranial pressure or shunt malfunction. A computed tomog-

HUMAN PATHOLOGY

Volume 25, No. 5 (May 1994)

raphy scan of the head showed diffuse ventricular enlargement, thinning of the cortical mantle with welldefined sulci, and a lipoma in the pineal region. The patient was anemic and had a coagulopathy that responded to vitamin K, fresh frozen plasma, and packed red blood cells. She underwent a choledochoduodenostomy for a common bile duct stricture. Four days before death her mental status deteriorated as she became obtunded and eventually unresponsive. Subsequently, she developed bronchopneumonia and died. PATHOLOGICAL

FINDINGS

Most strikingly, the autopsy showed macrocephaly (head circumference 89 cm). On opening the calvarium approximately 800 mL of cerebrospinal fluid was collected and the thin brain collapsed within the skull vault. There was dense irregular thickening of the skull base and all regions of the calvarium (1.7 cm thick), particularly the inner table, and diffuse ossification of the dura mater (Figs 1 and 2). The fresh brain weighed 1,060 g. Examination of the fixed brain showed diffuse microgyria with flattening of the microgyri and narrowing of the sulci. The brain had an ab normal globoid contour. Coronal sectioning showed thinning of the cortical gray matter and white matter, each measuring approximately 1 to 2 mm in thickness. Separating the cerebellum from the hemispheres showed a 1 X 1.5 cm lipoma involving the quadrigeminal plate and compressing the aqueduct. Microscopic examination of the skull was remarkable for thickened, sclerotic medullary bone with little evidence of osteoclastic or osteoblastic activity. The trabecular surfaces were smooth with a slight increase in reversal lines. The marrow fat appeared normal and there was no paratrabecular fibrosis. Examination under polarized light showed the majority of the

FIGURE 2. Gross photograph of skull base (frontal at top) showing diffuse thickening and distortion of osseous elements and obliterative ossification of basilar dura mater.

bone to be lamellar with foci of woven bone near regions of dural ossification. A non-decalcified section of bone examined with a modification of the Masson’s trichrome stain showed that the vast majority of the bone was mineralized with less than 5% of the estimated volume of bone examined exhibiting unmineralized osteoid. No active osteoblastic surfaces were identified to suggest enhanced rates of bone synthesis, and there was no evidence of increased osteoclastic activity. No histological evidence of any other processes (ie, Paget’s disease or osteopetrosis) was found (Fig 3). The thin neocortex showed extensive neuronal loss but no abnormalities in cortical lamination. The white matter showed disproportionately greater loss in volume than did the gray matter. There was loss of ependyma and ependymal granulations and periventricular areas contained remnants of germinal matrix. Sections through the spinal cord showed degeneration of the posterior columns with astrogliosis and, at lower levels, secondary degeneration of the corticospinal tract. Alzheimer’s type II astrocytes were identified in the deep gray matter. The lipoma was confirmed microscopically. The remainder of the autopsy was significant for acute bronchopneumonia, acute bilateral tracheobronchitis, acute renal tubular necrosis, and hepatomegaly (2,250 g) that microscopically showed bile stasis and diffuse centrolobular necrosis. DISCUSSION FIGURE 1. Computed tomography scan from terminal admission showing severe hydrocephalus and a markedly thickened skull.

Hyperostosis cranii ex vacua is a designation intended to distinguish marked calvarial thickening after effective shunting of hydrocephalus from thickening of the skull because of other causes. The inner table of the skull is extremely sensitive

CASE STUDIES

FIGURE 3. Photomicrograph of decalcified section of skull (left and right) showing thickening and sclerosis of cortical and cancellous bone. Examination under polarized light (right) shows a predominance of lamellar bone.

to changes in cerebral morphology and size throughout the life span of the individual. In progressive hydrocephalus marked enlargement of the skull occurs. If a successful shunt is placed, the growth pressure exerted by the brain against the skull is reduced and the calvarium may thicken, predominantly the inner table. Sutures play a role in this process because the sutures are remnants of the original membranous cranial capsule. The sutural area is the location where bone may be added for the separation of the calvarial bones as the brain expands. When growth pressure against them is reduced, the sutures fuse. Once the need for further compensatory separation of bones is removed, the membrane ossifies. This calvarial thickening and premature synostosis of sutures allow for little further expansion of the intracranial contents. Future normal brain development may be impeded depending on the size of skull and the age of the patient when premature closure of sutures occurs.1’4 Kurlander and Cht&’ reported that this laminated thickening of the calvarium may develop within several months of placing a ventricular shunt and has been associated with lowpressure Spitz-Holter valves. Such complications now preclude the use of these shunts4 Although our patient had multiple shunts and revisions, the paucity of detailed clinical data did not allow us to identify the exact type of shunt or the developmental progression of her macrocrania. The origins of symmetric macrocrania are not limited to shunt-treated hydrocephalus. Symmetric enlargement with secondary enlargement of the diploic space may be noted in anemia (thalassemia, sickle cell disease, or congenital spherocytosis) . However, these result in increased measurements of head circumference, but no concomitant increase in inner table-to-inner table measurements. On admission to our hospital the patient was anemic and remained so during her entire stay. Neither the duration of her anemia before hospitalization nor its clinical significance is known. Cerebral gigantism, or Soto’s syndrome, represents an idiopathic acceleration of head growth associated with cerebral atrophy and mental retardation. The ventricles are dilated and the

547

skull vault is enlarged, with frontal bossing, but is not otherwise unusual in shape. In hydranencephaly there is destruction of the cerebral mantle; the lateral ventricles are consequently dilated and surrounded by cerebral cortex that has been reduced to a thin membrane. Aqueductal obstructions also are common. The size of the hydranencephalic skull is usually normal at birth and often increases rapidly in the first few months of life. Children with dysostosis multiplex, or lipochondrodystrophy, exhibit dwarf stature with mental retardation, large skulls, puffy myxedematous skin, hepatospleno megaly, and cornea1 clouding. Skulls of patients with Hurler-Hunter syndrome are most impressive because of the thickness of the base of the calvarium and the absence of normal convolutions. Hydrocephalus in these patients is the result of fibrous thickening of the dura and leptomeninges (secondary to accumulation of glycosaminoglycans) that obstructs the subarachnoid space.” Sclerosteosis is an autosomal-recessive condition characterized by skeletal overgrowth of the cranium and mandible with broadening of the scapulae, pelvis, and vertebral bodies. Long bones typically show sclerotic changes. Other associations include syndactyly and digital malformation as well as cranial nerve impairment, such as facial palsy and deafness. In addition, elevated intracranial pressure may develop in these patients.6*’ Pathologically, sclerosteosis is considered to be a disorder of modeling and remodeling, localized particularly to the skull and diaphyseal region of long bones. The increased bone mass is thought to be the result of increased osteoblast activity leading to increased bone formation. The role of depressed osteoclastic activity in the pathogenesis has not been ruled out. Technetium 99 methylene diphosphonate scanning has shown increased bone turnover in the skull.’ The inward growth of the inner table of the skull caused by a marked diminution in intracranial volume is a rare but physiologically fitting accompaniment to arrested childhood hydrocephalus. The diagnosis is facilitated by the findings of cranial enlargement, premature closure of the sutures, and a histoty of appropriate shunting procedures. This lesion is of more than passing interest because even mild recurrent hydrocephalus caused by shunt failure may result in a catastrophic recrudescence of intracranial hypertension. Acknowledgmat. The authors gratefully acknowledge the confirmatory examinations of Dr Howard D. Dorfman, Professor of Ormopaedic Surgery, Pathology, and Radiology, Montefiore Medical Center/Albert Einstein College of Medicine and the photographic expertise of MS Karen Jensen.

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