Haemocytic Neoplasia of Clams

Category

Category 2 (In Canada and of Regional Concern)

Common, generally accepted names of the organism or disease agent

Haemocytic neoplasia of clams, Haematopoietic neoplasia, Hemic neoplasia, Softshell clam sarcoma, HCN, Disseminated neoplasia of clams, Disseminated sarcoma of softshell clams, Leukemia of softshell clams.

Scientific name or taxonomic affiliation

Cause unknown, possibly a viral aetiology (B-type retrovirus) (Appeldoorn and Oprandy 1980, Oprandy et al. 1981). Nevertheless, the fatal haematopoietic tumors of Mya arenaria have been defined as leukemias. A monoclonal antibody reagent suggests that leukemia cells, normal haemocytes and connective tissue cells may be otogenically related (Smolowitz et al. 1989, Smolowitz and Reinisch 1993).

Geographic distribution

  1. Eastern USA and eastern Canada
  2. Coast of British Columbia (Mya arenaria was introduced into San Francisco Bay in the mid-19th century and has subsequently spread along the Pacific coast to southeastern Alaska (MacNeil 1965, Quayle 1978). The neoplastic cells in M. arenaria from British Columbia reacted with the monoclonal antibodies of Smolowitz and Reinisch (1986) (pers. com. C. Reinisch, Email: creinisc@mbl.edu).
  3. Baffin Island, Canada
  4. Yaquina Bay, Oregon, USA
  5. Northern coast of Brittany, France; Spain and Ireland.

Host species

  1. Mya arenaria, Macoma baltica
  2. Mya arenaria
  3. Mya truncata
  4. Macoma irus, Macoma nasuta
  5. Cerastoderma edule; (oysters and mussels also affected but aetiology is probably different).

Impact on the host

Gradual appearance of neoplastic haemocytes throughout the soft-tissues (in the open vascular system including the large sinusoids which surround internal organs) with associated disruption of normal function of the haemocytes. Eventually 90-100% of the haemocytes are affected. Neoplastic cells fill and expand the vascular spaces resulting in stasis of haemolymph flow and compression of adjacent organs, and eventually the clam dies. At the terminal stages of the disease, the clam haemolymph is hypoxic and provides optimal conditions and possibly promoters (growth factors) for the proliferation of the neoplastic cells which can survive freezing and tolerate a wide range of salinity, temperature and pH (Sunila 2003).

Prevalence and effect of soft-shell clam haemocytic neoplasia varies significantly between areas (Barber 2004). Most clam populations from southeastern Canada to Massachusetts have shown no evidence of disease as a result of haemocytic proliferation. However, in 1999 high prevalences of infection (80 to >95%) were detected in association with mortalities of M arenaria in a few locations in Atlantic Canada (McGladdery et al. 2001a and b). Also, chronic mortalities ranging from 30-80% in populations of soft-shell clams in Chesapeake Bay since the early 1980s were attributed to this disease. Haemocytic neoplasia may be temperature related and previously unexposed clam populations are more susceptible than stocks with chronic levels of haemocytic neoplasia. In Chesapeake Bay, highest prevalence occur over fall and winter and individuals with severe disease tend to die during winter and in early spring. In Atlantic Canada, associated mortalities were detected during the summer months (McGladdery et al. 2001).

Some clams (16% of lightly infected M. arenaria in one field study) can undergo complete remission (Brousseau and Baglivo 1991). Mya arenaria with advanced stages of the disease showed complete exhaustion of some protease inhibitors in their plasma (Elsayed et al. 1999). A parallel in the distribution of disseminated neoplasia and the presence of certain dinoflagellate biotoxins has been reported (Landsberg 1996). Field data suggest that the presence of high levels of anthropogenic substances including proximity to agricultural activity and exposure to environmental pollutants such as polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons and possibly other effluents from pulp mills and aluminum smelters is directly correlated with environmentally linked haemocytic neoplasia in M. arenaria (McGladdery et al. 2001b). Environmentally induced alterations in p53 (the tumor suppressor gene that is commonly mutated in a broad range of human cancers) can contribute to the pathogenesis of haemocytic neoplasia in M. arenaria that inhabit polluted water and/or sediment (Barker et al. 1997).

In Galicia, Spain, disseminating neoplasia and large focis of intense haemocytic infiltration was associated with high mortalities of C. edule (Villalba et al. 2001) but this association was not consistent (Carballal et al. 2001). In Ireland, disseminating neoplasia in C. edule was found to be more prevalent during the early spring and autumn and less prevalent in winter and more prevalent in Cork Harbour than from cockles along the adjacent coast (Twomey and Mulcahy et al. 1988b).

Diagnostic techniques

Histocytology (Haemocytology): Examine haemocytes for characteristics described below. The diseased haemocytes round up and lack pseudopodial adhesion to the slide. Staining preparations with Feulgen Picromethyl Blue aids in the detection of neoplastic cells. Neoplastic cells stained with oil red O revealed 5 to 15 intensely stained vacuoles (presumably indicative of oil droplets) that were absent in normal haemocytes and these neoplastic cells were similar in morphology and staining properties to human Burkitt's lymphoma cells (Kelley et al. 2001).

Histology: Intense infiltration of abnormal haemocytes into the connective tissue, and haemolymph sinuses of the visceral mass, muscle and mantle tissue. Abnormal haemocytes are hypertrophied (2 to 4 times in diameter of normal haemocytes) with very little cytoplasm in relation to nucleoplasm and with enlarged and often pleomorphic nuclei and the presence of obvious mitotic figures.

Immunological Assay: Prevalence in a population of clams can be evaluated by staining haemolymph samples with the indirect peroxidase technique using monoclonal antibodies which recognizes specific proteins expressed by the diseased cells (Smolowitz and Reinisch 1986, 1993; Miosky et al. 1989)

Molecular characteristics: Homologues for human p53 and p73 cDNA (genes associated with various cancers in humans) and expression patterns for their corresponding proteins were identified in Mya arenaria with haemocytic neoplasia from New Bedford Harbor, Massachusetts, USA (Kelley et al. 2001, Walker et al. 2006)

Methods of control

Due to the clearly demonstrated contagious nature of HCN, every effort should be taken to avoid introducing affected stocks (currently or historically) regardless of the levels of the disease. To date, the possibility of cross-transmission (between species of bivalves) has not been demonstrated. The effect of the disease can be reduced by maintaining cultivated populations at as low a density as practical, harvesting prior to the typical period of increased mortality (fall and winter), and harvesting stocks as young as possible (since the severity of infection appears to increase with age).

References

Appeldoorn, R.S. and J.J. Oprandy. 1980. Tumors in soft-shell clams and the role played by a virus. Maritimes 24(3): 4-6.

Auffret, M. and M. Poder. 1986. Sarcomatous lesions in the cockle Cerastoderma edule. II. Electron microscopical study. Aquaculture 58: 9-15.

Barber, B.J. 2004. Neoplastic diseases of commercially important marine bivalves. Aquatic Living Resources 17: 449-466.

Barker, C.M., R.J. Calvert, C.W. Walker and C.L. Reinisch. 1997. Detection of mutant p53 in clam leukemia cells. Experimental Cell Research 232: 240-245.

Brand, D.G. and J.A.J. Thompson. 1997. Toxicological studies of fish and invertebrates in the Fraser River estuary. In: J. Luternaur and B. Groulx (eds.). The Fraser River Delta. Geological Survey of Canada and American Association for the Advancement in Science, p. In press.

Brousseau, D.J. 1987. Seasonal aspects of sarcomatous neoplasia in Mya arenaria (soft-shell clam) from Long Island Sound. Journal of Invertebrate Pathology 50: 269-276.

Brousseau, D.J. and J.A. Baglivo. 1991. Field and laboratory comparisons of mortality in normal and neoplastic Mya arenaria. Journal of Invertebrate Pathology 57: 59-65.

Carballal, M.J., D. Iglesias, J. Santamarina, B. Ferro-Soto and A. Villalba. 2001. Parasites and pathologic conditions of the cockle Cerastoderma edule populations of the coast of Galicia (NW Spain). Journal of Invertebrate Pathology 78: 87-97.

Cooper, K.R., R.S. Brown and P.W. Chang. 1982a. The course and mortality of a hematopoietic neoplasm in the soft-shell clam Mya arenaria. Journal of Invertebrate Pathology 39: 149-157.

Cooper, K.R., R.S. Brown and P.W. Chang. 1982b. Accuracy of blood cytological screening techniques for the diagnosis of a possible hematopoietic neoplasm in the bivalve mollusc Mya arenaria. Journal of Invertebrate Pathology 39: 281-289.

Elsayed, E.E., S.M. McLaughlin and M. Faisal. 1999. Protease inhibitors in plasma of the softshell clam Mya arenaria identification and effects of disseminated sarcoma. Comparative Biochemistry and Physiology 123B: 427-435.

Elston, R.A., J.D. Moore and K. Brooks. 1992. Disseminated neoplasia of bivalve molluscs. Reviews in Aquatic Sciences 6: 405-466.

Farley, C.A. 1976. Proliferative disorders in bivalve mollusks. Marine Fisheries Review 38(10): 30-33.

Farley, C.A., S.V. Otto and C.L. Reinisch. 1986. New occurrence of epizootic sarcoma in Chesapeake Bay soft shell clams Mya arenaria. Fisheries Bulletin 84(4): 851-857.

Farley, C.A., O.L. Plutschak and R.F. Scott. 1991. Epizootiology and distribution of transmissible sarcoma in Maryland softshell clams, Mya arenaria, 1984-1988. Environmental Health Perspectives 90: 35-41.

Harper, D.M., D.A. Flessas and C.L. Reinisch. 1994. Specific reactivity of leukemia cells to polyclonal anti-PCB antibodies. Journal of Invertebrate Pathology 64: 234-237.

Kelley, M.L., P. Winge, J.D. Heaney, R.E. Stephens, J.H. Farell, R.J. Van Beneden, C.L. Reinisch, M.P. Lesser and C.W. Walker. 2001. Expression of homologues for p53 and p73 in the softshell clam (Mya arenaria), a naturally-occurring model for human cancer. Oncogene 20: 748-758.

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MacNeil, F.S. 1965. Evolution and distribution of the genus Mya, and tertiary migrations of mollusca. Geological Survey Professional Paper 483-G: 1-51.

McGladdery, S.E., G.S. MacCallum, N.G. MacNair and J.T. Davidson. 2001a. Mass mortalities of soft-shell clams (Mya arenaria) in Atlantic Canada associated with unprecedented levels of hemic neoplasia. Journal of Shellfish Research 20: 549. (Abstract).

McGladdery, S.E., C.L. Reinisch, G.S. MacCallum, R.E. Stephens, C.L. Walker and J.T. Davidson. 2001b. Haemic neoplasia in soft-shell clams (Mya arenaria): recent outbreaks in Atlantic Canada and discovery of a p53 gene homologue associated with the condition. Bulletin of the Aquaculture Association of Canada 101-3: 19-26.

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Oprandy, J.J., P.W. Chang, A.D. Pronovost, K.R. Cooper, R.S. Brown and V.J. Yates. 1981. Isolation of a viral agent causing hematopoietic neoplasia in the soft-shell clam Mya arenaria. Journal of Invertebrate Pathology 38: 45-51.

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Smolowitz, R.M. and C.L. Reinisch. 1993. A novel adhesion protein expressed by ciliated epithelium, hemocytes, and leukemia cells in soft-shell clams. Developmental and Comparative Immunology 17: 475-481.

Smolowitz, R.M., D. Miosky and C.L. Reinisch. 1989. Ontogeny of leukemic cells of the soft shell clam. Journal of Invertebrate Pathology 53: 41-51.

Sunila, I. 1992. Serum-cell interactions in transmission of sarcoma in the soft shell clam Mya arenaria L. Comparative Biochemistry and Physiology 102A: 727-730.

Sunila, I. 2003. Disseminated sarcoma in the soft shell clam (Mya arenaria) - physiological and molecular aspects. In: Hendry, C.I. (ed.), Aquaculture Canada 2002 - Proceedings of the Contributed Papers of the 19th Annual Meeting of the Aquaculture Association of Canada, Charlottetown, PEI, May 17-20, 2002. Aquaculture Association of Canada Special Publication Number 6, 2003, Moncton, NB, pp. 56-59.

Sunila, I. and C.F. Dungan. 1992. Different proteins in the hemolymph sera from sarcomatous and healthy soft shell clams, Mya arenaria L. Comparative Biochemistry and Physiology 102B: 621-625.

Twomey, E. and M.F. Mulcahy. 1988a. Transmission of a sarcoma in the cockle Cerastoderma edule (Bivalvia; Mollusca) using cell transplants. Developmental and Comparative Immunology 12: 195-200.

Twomey, E. and M.F. Mulcahy. 1988b. Epizootiological aspects of a sarcoma in the cockle Cerastoderma edule. Diseases of Aquatic Organisms 5: 225-238.

Villalba, A., M.J. Carballal and C. López. 2001. Disseminated neoplasia and large foci indicating heavy haemocytic infiltration in cockles Cerastoderma edule from Galicia (NW Spain). Diseases of Aquatic Organisms 46: 213-216.

Walker, C., S. Böttger and B. Low. 2006. Mortalin-based cytoplasmic sequestration of p53 in a nonmammalian cancer model. American Journal of Pathology 168: 1526-1530.

Weinberg, J.R., D.F. Leavitt, B.A. Lancaster and J. McDowell Capuzzo. 1997. Experimental field studies with Mya arenaria (Bivalvia) on the induction and effect of hematopoietic neoplasia. Journal of Invertebrate Pathology 69: 183-194.

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Citation Information

Bower, S.M. (2006): Synopsis of Infectious Diseases and Parasites of Commercially Exploited Shellfish: Haemocytic Neoplasia of Clams.

Date last revised: December 2006
Comments to Susan Bower

Date modified: