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Intraglandular toxoplasmosis of the parotid gland pre- or postoperative diagnosis?
American Journal of Otolaryngology–Head and Neck Medicine and Surgery 28 (2007) 201 – 204 www.elsevier.com/locate/amjoto
Intraglandular toxoplasmosis of the parotid gland pre- or postoperative diagnosis? Usamah Hadi, MD, FACS4, Charbel Rameh, MD Department of Otolaryngology-Head and Neck Surgery, American University of Beirut Medical Center, Beirut, Lebanon Received 9 February 2006
Abstract
Toxoplasmosis is an ubiquitous protozoan infection, caused by the coccidian Toxoplasma gondii. It usually presents clinically with lymphadenopathy, mainly in the head and neck region. However, in the English literature, very scarce cases of intraparotid Toxoplasma exist, none having been diagnosed preoperatively. In this article, we present 2 cases of intraglandular parotid toxoplasmosis, one diagnosed postoperatively and the other preoperatively. We also review the relevant literature concerning Toxoplasma infection of the parotid gland. D 2007 Elsevier Inc. All rights reserved.
1. Introduction Toxoplasmosis is a parasitic infection caused by the organism Toxoplasma gondii. It is acquired from ingestion of infected meat, blood transfusions, and organ transplantation. An English literature review using Medline and PubMed dating back to 1966 has revealed only scarce reports of intraglandular toxoplasmosis of the parotid gland. In this report, we present 2 cases of toxoplasmosis of the parotid gland, the first having been diagnosed retrospectively after reviewing the postoperative pathology and the second prospectively by having had a high index of suspicion. 2. Case reports 2.1. Case 1 A 35-year-old male patient presented with a 2-month history of a progressive, painless, left parotid enlargement, unresponsive to antibiotic treatment. He denied any history of travel or exposure to pets. Physical examination revealed a diffuse nontender swelling of the left parotid gland,
4 Corresponding author. Department of Otolaryngology-Head and Neck Surgery, PO Box 11-0236-B18, American University of Beirut Medical Center, Beirut, Lebanon. Tel.: +961 1 350 000x5470; fax: +961 1 370 793. E-mail addresses: [email protected] (U. Hadi)8 [email protected] (C. Rameh). 0196-0709/$ – see front matter D 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.amjoto.2006.08.006
suspicious of a parotid tumor. He thus underwent a left superficial parotidectomy. Pathologic examination revealed normally lobulated glandular tissue, with preserved lymph node architecture. Follicular and interfollicular hyperplasia was present, and numerous granulomata made up of epithelioid cells were scattered and impinging focally upon the lymphoid follicles. These findings of intraparotid granulomatous lymphadenitis were suggestive of toxoplasmosis. Retrospectively, Toxoplasma serum titers were taken and were strongly positive: Toxoplasma immunoglobulin G (IgG) was 206 IU/mL (normal, b8 IU/mL) and Toxoplasma immunoglobulin M (IgM) was 6.40 IU/mL (normal, b 0.65 IU/mL). Two weeks postoperatively, the patient started again to have an enlargement of his left parotid gland. He then received a course of rovamycin (spiramycin) 1.5 g BID, which resulted in significant regression of his parotid enlargement. Repeat IgG 6 months later was still elevated (300 IU/mL), but IgM had dropped to 0.84. On follow-up 24 months postoperatively, the patient was still free of recurrence. 2.2. Case 2 A 12-year-old boy presented with a 5-month history of a progressively enlarging left parotid gland mass, which is 2 3 cm in size, nonfixed, nonerythematous, and nonpainful. He denied any history of travel or exposure
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Fig. 1. Computed tomography scan of intraparotid Toxoplasma mimicking a tumor.
to pets. Neck examination was otherwise normal. Serologic workup revealed elevated T gondii IgG, with a value of 106 (normal, b8 IU/mL), but Toxoplasma IgM was negative (0.55). Computed tomography revealed a large intraparotid mass (Fig. 1). The patient was treated with amoxicillin/clavulanate and rovamycin with no response. Repeat computed tomography scan revealed the same unchanged persistent mass. Fine needle aspiration (FNA) was then done revealing reactive lymph nodes. Follow-up Toxoplasma IgG was found to be increasing (129 IU/mL). In view of all these findings, the patient underwent a left superficial parotidectomy. Pathologic examination revealed 2 enlarged intraparotid lymph nodes with preserved architecture and showing the characteristic histologic triad found in toxoplasmosis (Fig. 2). Postoperatively, the patient received rovamycin, and on follow-up 24 months later, he was still free of recurrence. 3. Discussion Toxoplasmosis is a ubiquitous infection caused by the protozoan Toxoplasma gondii. Positive Toxoplasma serology is present in 10% to 20% of young individuals, and in as much as 35% to 70% of the older population [1]. In one review of 8070 cases of salivary gland disease, only 16 were diagnosed with intraglandular Toxoplasma lymphadenitis of the parotid or submaxillary glands [2]. Since this review, 8 cases of parotid toxoplasmosis have been reported in the English literature, none of which having been diagnosed preoperatively (Table 1), as was the case with our second patient. The definitive host of Toxoplasma is the domestic cat, and its life cycle includes both a sexual phase and an asexual phase, details of which are not the focus of this article. Clinically, most Toxoplasma-seropositive patients are asymptomatic. Otherwise, the most frequently encountered
Fig 2. (A) Intraparotid lymph node with follicular hyperplasia, (hematoxylin-eosin stain, original magnification 4). (B) Clusters of proliferating epithelioid histiocytes, with a mixed lymphocytic and immunoblastic cell population (hematoxylin-eosin stain, original magnification 20). (C) Distension of marginal and cortical sinuses with epithelioid cells (hematoxylin-eosin stain, original magnification 20).
U. Hadi, C. Rameh / American Journal of Otolaryngology–Head and Neck Medicine and Surgery 28 (2007) 201–204
clinical manifestation is posterior cervical lymphadenitis. Other symptoms include fever, myalgias, sore throat, and a papular rash. In immunocompromised hosts, a more systemic form prevails, with multiple organ involvement, including the central nervous system [3]. However, its presentation as a parotid mass secondary to involvement of the 2 to 30 intraglandular nodes found within the parotid gland, mostly in its superficial lobe, is a rare occurrence [4]. The most reliable technique for the diagnosis of toxoplasmosis is tissue cultures, or to isolate the parasite from an infected tissue or body fluid by intraperitoneal inoculation of mice. However, because these techniques are not routinely done, serologic tests have been the major tool for the diagnosis of toxoplasmosis, in conjunction with the findings on lymph node histology. For the diagnosis of a suspected case of acute toxoplasmosis, IgG and IgM serology has been the main clinical test performed. Immunoglobulin G antibodies become positive 2 to 3 weeks after infection, achieve a peak concentration 1 to 2 months later, and remain positive indefinitely [1] (Graph 1). A serial 2-tube 4-fold rise in titer is required for confirmation of active infection. On the other hand, IgM antibodies can be detected 2 weeks after infection, achieve peak concentrations in 1 month, decrease thereafter, and usually become undetectable within 6 to 9 months (Graph 1). A single IgM titer of 1:80 or higher is diagnostic, but a negative result does not rule out infection. Immunoglobulin E antibodies also appear early in the infection and disappear in less than 3 to 5 months, and are therefore suitable for the diagnosis of early acute infection. Histologically, the diagnostic triad for diagnosing toxoplasmosis is characteristic and was described in Fig. 2 [5]. In this article, we have presented 2 cases of intraglandular parotid toxoplasmosis. The first case was diagnosed retrospectively after reviewing the pathology specimen. A rapid disease recurrence 2 weeks after the surgery was then successfully treated with rovamycin. In this patient, the pattern of antibody level variations coincided with that described in the literature, with IgG rising in 4 to 8 weeks and remaining elevated, and IgM dropping back to normal. In the second case, we reported the first described preoperative diagnosis of parotid gland toxoplasmosis in the English literature. In this case, IgG was positive at presentation, but IgM was negative, compatible with an old Toxoplasma infection [1,4]. The low IgM titer Table 1 Intraparotid toxoplasmosis cases since 1986
203
Graph 1. Relative variations in immunoglobulin titers in toxoplasmosis.
was probably due to the late presentation of this patient in the course of his illness. In general, the clinical course of toxoplasmosis is selflimited. Treatment is unnecessary unless clinical symptoms are severe or persistent, or unless the patient is immunocompromised. In intraglandular toxoplasmosis of the parotid where the clinical diagnosis is compromised, persistence of intraparotid lymphadenopathy would warrant a superficial parotidectomy, and most of these cases after appropriate diagnosis would require systemic antibiotic treatment to prevent an early recurrence as what occurred in our first patient. The therapy of choice is a combination of pyrimethamine and sulfadiazine, or rovamycin, but because pyrimethamine is a folic acid antagonist, 5 to 10 mg of folinic acid should be administered daily. The activity of these drugs is limited to tachyzoites, and not to the cyst form. Therefore, daily maintenance therapy for life is necessary for immunocompromised patients [5]. Finally, 2 questions arise and remain unanswered. First, in parotid toxoplasmosis, controversy exists in differentiating between a recent onset of acute Toxoplasma infection vs a reactivation of an old infection, especially when only IgG titers are elevated, IgM titers are low, and tissue cultures are lacking. A second question is whether intraparotid masses, associated with a positive Toxoplasma serology, would resolve spontaneously or on medical treatment, or whether they would necessitate FNA vs a superficial parotidectomy for definitive diagnosis. Our second case failed preoperative medical treatment, and ultimately required surgery. However, more cases are needed to answer this question in the future.
Author(s)
Year
No. of cases
References
Moran et al [1] Pittam and Thomas [6] Von Arx [7] Camacho et al [3] Akiner et al [4] Langford and Whear [8]
1986 1987 1988 1989 1991 2000
1 3 1 1 1 1
[1] Moran WJ, Tom DW, King GD, et al. Toxoplasmosis lymphadenitis occurring in a parotid gland: pathology-diagnosis-treatment-facial nerve surgery. Otolaryngol Head Neck Surg 1986;94(2):237 - 40. [2] Seifert G. Diseases of the salivary glands: pathology-diagnosistreatment-facial nerve surgery. In: Miehlke A, Haubrich J, Chilla R, editors. New York7 Thieme Inc; 1986. p. 302 - 3.
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U. Hadi, C. Rameh / American Journal of Otolaryngology–Head and Neck Medicine and Surgery 28 (2007) 201–204
[3] Camacho AE, Goodman ML, Eavey RD. Pathologic correlation of the unknown solid parotid mass in children. Otolaryngol Head Neck Surg 1989;101(5):566 - 71. [4] Akiner MN, Saatci MR, Yilmaz O, et al. Intraglandular toxoplasmosis lymphadenitis of the parotid gland. J Laryngol Otol 1991;105(10):860 - 2. [5] Sun T. Parasitic disorders, pathology, diagnosis, and management. Baltimore, MD: Williams and Wilkins, 1999. p. 99 - 110.
[6] Pittam M, Thomas M. Diseases of the pre-auricular lymph nodes mimicking parotid tumors. Br J Surg 1987;74:1172 - 3. [7] Von Arx DP. Cervicofacial toxoplasmosis. Br J Oral Maxillofac Surg 1988;26(1):70 - 7. [8] Langford R, Whear N. Serology should be a routine investigation when presented with a major salivary gland lump. Br J Oral Maxiofac Surg 2000;38:158 - 9.
Intraglandular toxoplasmosis of the parotid gland pre- or postoperative diagnosis? Usamah Hadi, MD, FACS4, Charbel Rameh, MD Department of Otolaryngology-Head and Neck Surgery, American University of Beirut Medical Center, Beirut, Lebanon Received 9 February 2006
Abstract
Toxoplasmosis is an ubiquitous protozoan infection, caused by the coccidian Toxoplasma gondii. It usually presents clinically with lymphadenopathy, mainly in the head and neck region. However, in the English literature, very scarce cases of intraparotid Toxoplasma exist, none having been diagnosed preoperatively. In this article, we present 2 cases of intraglandular parotid toxoplasmosis, one diagnosed postoperatively and the other preoperatively. We also review the relevant literature concerning Toxoplasma infection of the parotid gland. D 2007 Elsevier Inc. All rights reserved.
1. Introduction Toxoplasmosis is a parasitic infection caused by the organism Toxoplasma gondii. It is acquired from ingestion of infected meat, blood transfusions, and organ transplantation. An English literature review using Medline and PubMed dating back to 1966 has revealed only scarce reports of intraglandular toxoplasmosis of the parotid gland. In this report, we present 2 cases of toxoplasmosis of the parotid gland, the first having been diagnosed retrospectively after reviewing the postoperative pathology and the second prospectively by having had a high index of suspicion. 2. Case reports 2.1. Case 1 A 35-year-old male patient presented with a 2-month history of a progressive, painless, left parotid enlargement, unresponsive to antibiotic treatment. He denied any history of travel or exposure to pets. Physical examination revealed a diffuse nontender swelling of the left parotid gland,
4 Corresponding author. Department of Otolaryngology-Head and Neck Surgery, PO Box 11-0236-B18, American University of Beirut Medical Center, Beirut, Lebanon. Tel.: +961 1 350 000x5470; fax: +961 1 370 793. E-mail addresses: [email protected] (U. Hadi)8 [email protected] (C. Rameh). 0196-0709/$ – see front matter D 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.amjoto.2006.08.006
suspicious of a parotid tumor. He thus underwent a left superficial parotidectomy. Pathologic examination revealed normally lobulated glandular tissue, with preserved lymph node architecture. Follicular and interfollicular hyperplasia was present, and numerous granulomata made up of epithelioid cells were scattered and impinging focally upon the lymphoid follicles. These findings of intraparotid granulomatous lymphadenitis were suggestive of toxoplasmosis. Retrospectively, Toxoplasma serum titers were taken and were strongly positive: Toxoplasma immunoglobulin G (IgG) was 206 IU/mL (normal, b8 IU/mL) and Toxoplasma immunoglobulin M (IgM) was 6.40 IU/mL (normal, b 0.65 IU/mL). Two weeks postoperatively, the patient started again to have an enlargement of his left parotid gland. He then received a course of rovamycin (spiramycin) 1.5 g BID, which resulted in significant regression of his parotid enlargement. Repeat IgG 6 months later was still elevated (300 IU/mL), but IgM had dropped to 0.84. On follow-up 24 months postoperatively, the patient was still free of recurrence. 2.2. Case 2 A 12-year-old boy presented with a 5-month history of a progressively enlarging left parotid gland mass, which is 2 3 cm in size, nonfixed, nonerythematous, and nonpainful. He denied any history of travel or exposure
202
U. Hadi, C. Rameh / American Journal of Otolaryngology–Head and Neck Medicine and Surgery 28 (2007) 201–204
Fig. 1. Computed tomography scan of intraparotid Toxoplasma mimicking a tumor.
to pets. Neck examination was otherwise normal. Serologic workup revealed elevated T gondii IgG, with a value of 106 (normal, b8 IU/mL), but Toxoplasma IgM was negative (0.55). Computed tomography revealed a large intraparotid mass (Fig. 1). The patient was treated with amoxicillin/clavulanate and rovamycin with no response. Repeat computed tomography scan revealed the same unchanged persistent mass. Fine needle aspiration (FNA) was then done revealing reactive lymph nodes. Follow-up Toxoplasma IgG was found to be increasing (129 IU/mL). In view of all these findings, the patient underwent a left superficial parotidectomy. Pathologic examination revealed 2 enlarged intraparotid lymph nodes with preserved architecture and showing the characteristic histologic triad found in toxoplasmosis (Fig. 2). Postoperatively, the patient received rovamycin, and on follow-up 24 months later, he was still free of recurrence. 3. Discussion Toxoplasmosis is a ubiquitous infection caused by the protozoan Toxoplasma gondii. Positive Toxoplasma serology is present in 10% to 20% of young individuals, and in as much as 35% to 70% of the older population [1]. In one review of 8070 cases of salivary gland disease, only 16 were diagnosed with intraglandular Toxoplasma lymphadenitis of the parotid or submaxillary glands [2]. Since this review, 8 cases of parotid toxoplasmosis have been reported in the English literature, none of which having been diagnosed preoperatively (Table 1), as was the case with our second patient. The definitive host of Toxoplasma is the domestic cat, and its life cycle includes both a sexual phase and an asexual phase, details of which are not the focus of this article. Clinically, most Toxoplasma-seropositive patients are asymptomatic. Otherwise, the most frequently encountered
Fig 2. (A) Intraparotid lymph node with follicular hyperplasia, (hematoxylin-eosin stain, original magnification 4). (B) Clusters of proliferating epithelioid histiocytes, with a mixed lymphocytic and immunoblastic cell population (hematoxylin-eosin stain, original magnification 20). (C) Distension of marginal and cortical sinuses with epithelioid cells (hematoxylin-eosin stain, original magnification 20).
U. Hadi, C. Rameh / American Journal of Otolaryngology–Head and Neck Medicine and Surgery 28 (2007) 201–204
clinical manifestation is posterior cervical lymphadenitis. Other symptoms include fever, myalgias, sore throat, and a papular rash. In immunocompromised hosts, a more systemic form prevails, with multiple organ involvement, including the central nervous system [3]. However, its presentation as a parotid mass secondary to involvement of the 2 to 30 intraglandular nodes found within the parotid gland, mostly in its superficial lobe, is a rare occurrence [4]. The most reliable technique for the diagnosis of toxoplasmosis is tissue cultures, or to isolate the parasite from an infected tissue or body fluid by intraperitoneal inoculation of mice. However, because these techniques are not routinely done, serologic tests have been the major tool for the diagnosis of toxoplasmosis, in conjunction with the findings on lymph node histology. For the diagnosis of a suspected case of acute toxoplasmosis, IgG and IgM serology has been the main clinical test performed. Immunoglobulin G antibodies become positive 2 to 3 weeks after infection, achieve a peak concentration 1 to 2 months later, and remain positive indefinitely [1] (Graph 1). A serial 2-tube 4-fold rise in titer is required for confirmation of active infection. On the other hand, IgM antibodies can be detected 2 weeks after infection, achieve peak concentrations in 1 month, decrease thereafter, and usually become undetectable within 6 to 9 months (Graph 1). A single IgM titer of 1:80 or higher is diagnostic, but a negative result does not rule out infection. Immunoglobulin E antibodies also appear early in the infection and disappear in less than 3 to 5 months, and are therefore suitable for the diagnosis of early acute infection. Histologically, the diagnostic triad for diagnosing toxoplasmosis is characteristic and was described in Fig. 2 [5]. In this article, we have presented 2 cases of intraglandular parotid toxoplasmosis. The first case was diagnosed retrospectively after reviewing the pathology specimen. A rapid disease recurrence 2 weeks after the surgery was then successfully treated with rovamycin. In this patient, the pattern of antibody level variations coincided with that described in the literature, with IgG rising in 4 to 8 weeks and remaining elevated, and IgM dropping back to normal. In the second case, we reported the first described preoperative diagnosis of parotid gland toxoplasmosis in the English literature. In this case, IgG was positive at presentation, but IgM was negative, compatible with an old Toxoplasma infection [1,4]. The low IgM titer Table 1 Intraparotid toxoplasmosis cases since 1986
203
Graph 1. Relative variations in immunoglobulin titers in toxoplasmosis.
was probably due to the late presentation of this patient in the course of his illness. In general, the clinical course of toxoplasmosis is selflimited. Treatment is unnecessary unless clinical symptoms are severe or persistent, or unless the patient is immunocompromised. In intraglandular toxoplasmosis of the parotid where the clinical diagnosis is compromised, persistence of intraparotid lymphadenopathy would warrant a superficial parotidectomy, and most of these cases after appropriate diagnosis would require systemic antibiotic treatment to prevent an early recurrence as what occurred in our first patient. The therapy of choice is a combination of pyrimethamine and sulfadiazine, or rovamycin, but because pyrimethamine is a folic acid antagonist, 5 to 10 mg of folinic acid should be administered daily. The activity of these drugs is limited to tachyzoites, and not to the cyst form. Therefore, daily maintenance therapy for life is necessary for immunocompromised patients [5]. Finally, 2 questions arise and remain unanswered. First, in parotid toxoplasmosis, controversy exists in differentiating between a recent onset of acute Toxoplasma infection vs a reactivation of an old infection, especially when only IgG titers are elevated, IgM titers are low, and tissue cultures are lacking. A second question is whether intraparotid masses, associated with a positive Toxoplasma serology, would resolve spontaneously or on medical treatment, or whether they would necessitate FNA vs a superficial parotidectomy for definitive diagnosis. Our second case failed preoperative medical treatment, and ultimately required surgery. However, more cases are needed to answer this question in the future.
Author(s)
Year
No. of cases
References
Moran et al [1] Pittam and Thomas [6] Von Arx [7] Camacho et al [3] Akiner et al [4] Langford and Whear [8]
1986 1987 1988 1989 1991 2000
1 3 1 1 1 1
[1] Moran WJ, Tom DW, King GD, et al. Toxoplasmosis lymphadenitis occurring in a parotid gland: pathology-diagnosis-treatment-facial nerve surgery. Otolaryngol Head Neck Surg 1986;94(2):237 - 40. [2] Seifert G. Diseases of the salivary glands: pathology-diagnosistreatment-facial nerve surgery. In: Miehlke A, Haubrich J, Chilla R, editors. New York7 Thieme Inc; 1986. p. 302 - 3.
204
U. Hadi, C. Rameh / American Journal of Otolaryngology–Head and Neck Medicine and Surgery 28 (2007) 201–204
[3] Camacho AE, Goodman ML, Eavey RD. Pathologic correlation of the unknown solid parotid mass in children. Otolaryngol Head Neck Surg 1989;101(5):566 - 71. [4] Akiner MN, Saatci MR, Yilmaz O, et al. Intraglandular toxoplasmosis lymphadenitis of the parotid gland. J Laryngol Otol 1991;105(10):860 - 2. [5] Sun T. Parasitic disorders, pathology, diagnosis, and management. Baltimore, MD: Williams and Wilkins, 1999. p. 99 - 110.
[6] Pittam M, Thomas M. Diseases of the pre-auricular lymph nodes mimicking parotid tumors. Br J Surg 1987;74:1172 - 3. [7] Von Arx DP. Cervicofacial toxoplasmosis. Br J Oral Maxillofac Surg 1988;26(1):70 - 7. [8] Langford R, Whear N. Serology should be a routine investigation when presented with a major salivary gland lump. Br J Oral Maxiofac Surg 2000;38:158 - 9.