Oral cysticercosis: A contribution of dentists & clinicians to One Health?

Historical account

Cysticercosis was first described by Johannes Udalric Rumler in 1555 but the connection between tapeworms and cysticercosis in man was still a mystery. In 1855, Kuchenmaister established that human cysticercosis is indeed caused by the larval stage, Cysticercus cellulosae, of the pork tapeworm, Taenia solium^[14].

Epidemiology

Cysticercosis is prevalent in several parts of the world. It is endemic and one of the leading causes of acquired epilepsy^[10] in developing countries, mainly in parts of Asia, Africa, Latin America and Eastern Europe. This is especially in those areas with uncontrolled free range pig production, poor sanitation and where humans and animals live in close contact^[1]. Its incidence is also increasing in developed countries as a result of migration of infected persons and frequent travel to and from endemic areas^[27].

In man, cysticercosis frequently involves many parts of the body including the brain (causing fatal neurocysticercosis), subcutaneous tissues, heart, liver, lungs, peritoneum, skeletal muscles and the eye. Although oral involvement by cysticercosis is common in swine, this location is a very rare occurrence in humans^{[17, 27, 1]} where it presents as a component of disseminated cysticercosis and often a diagnostic challenge to clinicians ^[14].

A literature review conducted in 2012 by Krishnamoorthy and colleagues  ^[14], revealed 69 cases of oral cysticercosis characterized by a cystic swelling as the only evidence of the disease. They further found that any region of the oral cavity can be involved but review of literature suggested that the tongue was the preferred site comprising 46.37% of the 69 cases, followed by labial and buccal mucosa, with one case documented involving the gingival tissue from India ^[17]. However, some authors postulate that the muscular activity and high metabolic rate of the oral region may prevent lodging of the cysticerci in the tongue^[5]. Other authors have also noted that intraorally, the favored sites for the development of cysticerci are the tongue, labial mucosa (lips), buccal mucosa (cheeks) and the floor of the mouth, however, correct and precise diagnosis is infrequently established ^{[20, 6, 23, 13, 29, 7, 12]}

How does man get infected?

Man is the definitive host for the adult pork tapeworm (Taenia solium) while the pig serves as an intermediate host. Human beings are infected by either:

1. Eating uncooked, partially cooked or inadequately frozen pork containing viable Cysticercus cellulosae.
2. Ingesting food or water contaminated by infected human faeces containing Taenia solium eggs which further explains cases of cysticercosis in vegetarians ^[11]
3. Autoinfection by regurgitation of eggs into the stomach after reverse peristalsis^{[20, 3, 24]}

In the human body the larval form (Cysticercus cellulosae) penetrates the intestinal mucosa and is then distributed through the blood vessels and lymphatics to the various parts of the body where they develop into cysticerci completing the life cycle.

What are the clinical signs?

In humans cysticercosis can develop in various organs and tissues. The larval form (Cysticercus cellulosae) commonly presents as a cyst in the cerebral tissue (brain), meninges, subcutaneous tissue, muscle and the eye ^{[3, 19, 13, 15]}. However, it is not commonly considered in the diagnosis of swellings of the maxillofacial region including the oral cavity and cheek muscles.

Most oral presentations of cysticercosis are in the form of painless, well-circumscribed, soft swellings or cystic nodules^[12], that may persist or rupture and heal uneventfully^[11]. Therefore, oral cysticercosis is a diagnostic challenge to a clinician due to:

1. The condition mimics other oral nodular lesions like mucoceles, or a benign tumor of mesenchymal origin, such as a lipoma, fibroma, hemangioma, granular cell tumor, or a minor salivary gland adenoma^[22]. However, the high intraluminal pressure in oral cysticercosis helps to differentiate it from lipoma and hemangioma.
2. Cysticercosis is rarely included in the pre-operative differential diagnosis due to relative rarity of the lesion, inadequate knowledge of oral manifestations of parasitic infections and negligence while taking medical history^[26].

Generally, the clinical symptoms of cysticercosis depend on the site and the number of cysticerci in the body. Cysticerci are well tolerated in the tissues when they are alive but evoke an inflammatory reaction in the surrounding tissue on  death. During invasion there may be no symptoms or mild muscular pain and fever. Central nervous system involvement may result to the potentially fatal neuro-cysticercosis^[9].

Examples of oral cysticercosis case presentation and presumptive diagnosis: 

Example one, Joshi and colleagues (2014)^[12]: An 18 year old male from Central India with an asymptomatic solitary cystic nodule in the right mucobuccal fold of upper arch. The patient reported that the lesion was present since 5-6 years with no associated pain. Intra oral examination revealed that the nodule as spherical in shape, 2 x 2 cm in size, firm, smooth surfaced and mobile. Noted in the alveolar mucosa mainly in mucobuccal fold of maxillary right canine region. There was no much change in the size and other features of the lesion in due course. The patient was otherwise healthy without any systemic signs and symptoms.

Example two, Bhatia and colleagues (2014)^[1]: A case of eight year old Hindu female and a resident of a slum in Mumbai. The patient came with a swelling inside the oral cavity on the right buccal mucosa since one year which gradually increased in size. On local examination the swelling was non tender, firm and mobile measuring 1 x 0.5cm.

Example three, Wanjari and colleages (2013)^[28]: Clinical presentation for both (2) cases was of diffuse, nontender, soft to fluctuant swelling. Case 1 showed involvement of the right cheek in the lower third of the face in line with the outer canthus of the right eye; however, intraorally overlying mucosa was intact and normal in colour. While case 2 revealed involvement of right labial mucosa in relation to maxillary right anterior region. No submandibular or cervical lymphadenopathy was detected in both cases.

Example four, Venkatraman and colleagues (2013)^[27]: A 23 year old male presented with a swelling on the right lateral border of the tongue. The patient reported that the lesion was present since 4 years with no associated pain. Intra oral examination revealed that the lesion was spherical in shape, 2×2 cm in size, firm, compressible, smooth surfaced and mobile within the soft tissue of the tongue.

Example five, Chunduri and colleagues(2013) ^[2]: A 17 year old Indian male presented with a nodule in the right lower lip. Clinical examination revealed a well circumscribed, mobile nodule approximately 1.5 cm in diameter with intact overlying mucosa. The lesion was painless and had been present for about six months, and was slowly growing.

Example six, Neves Santos and colleagues (2013)^[21]: A 21-year-old woman from Poções County (Bahia, Brazil) reported to a private dental center with the chief complaint of a painless nodule on the right side of her tongue that had been present for the past two years. The nodule had increased in size to approximately 3.5 cm in maximum diameter, and clinical examination showed a firm nodule that was covered with normal mucosa. No cervical or submandibular lymphadenopathy was observed. A complete blood count, liver function tests and renal function tests were all normal. A preliminary diagnosis of lipoma was made.

Example seven, Krishnamoorthy and colleagues (2012)^[14]: A 12-year-old girl with a nodular swelling on the lower lip. She first noticed it 2 months ago. The swelling was painless, remained unchanged in size, and caused a little difficulty while eating and talking. On examination there was a solitary, spherical, well-defined swelling in the lower labial mucosa present on the left side of the midline which measured approximately 1.5 X 1.5 cm. The mucosa over the swelling was normal. On palpation it was not tender, but was tense and nonfluctuant. Differential diagnoses of mucocele, lipoma, and fibroma were considered.

Diagnosis of oral cysticercosis  

Diagnosis of human oral cysticercosis (including other forms of tissue cysticercosis) is impaired by its polymorphic clinical presentations. Excisional biopsy coupled with sections stained with Haematoxylin & Eosin, is the only confirmatory diagnostic procedure for the condition, which demonstrates the presence of the larva in the tissue or the scolex in the cystic lesion. However, other investigations must be considered to detect the disease in the diverse tissues that may be affected, using: Fine Needle Aspiration (FNA), serology, radiologic imaging techniques such as Computer Tomography (CT) or Magnet Resonance Imaging (MRI) and advanced molecular techniques as tools for conformational diagnosis^[5][7].

Criteria for diagnosing oral cysticercosis as proposed by Krishnamoorthy and colleagues is: ^[14]:

• A compatible clinical presentation
• FNA aspirated material showing a speck of pearly white content also by^{[17, 27]}
• Histopathologic demonstration of the parasite on biopsy
• Cystic lesions with scolex on imaging (muscular cysticercosis)
• Positive epidemiological factors like household contact, endemic region or travel to or from an endemic area

Examples of oral cysticercosis definitive diagnoses: 

Example one, Joshi and colleagues (2014)^[12]: Microscopically, the excised tissue showed a thin fibrous connective tissue capsule adjacent to a cystic cavity containing a duct like tubal segments that was lined by a homogeneous membrane typical of cysticercosis cellulosae (larval form of Taenia solium); Cyst wall and outer fibrous tissue was presenting in many papillary projections along with numerous inflammatory cell infiltrations and macrophages.

Example two, Bhatia and colleagues (2014)^[1]: External fibrous capsule with mononuclear cell infiltrate comprised of lymphocytes, histocytes and plasma cells. A double layered membrane consisting of an outer acellular hyaline eosinophilic layer and an inner sparsely cellular layer with aggregates of eosinophils was seen. The cyst contained larval form of T. Solium. The cephalic extremity of larva (scolex) with suckers could be identified suggesting the diagnosis of cysticercosis of right buccal mucosa.

Example three, Wanjari and colleagues (2013)^[28]: Histopathological examination of excisional biopsy specimen revealed external dense, fibrous capsule derived from host tissue surrounding a cystic cavity which contained larval stage of T solium-cysticercus cellulosae. capsule showed intense inflammatory infiltrate consisting of plasma cells and few eosinophils. The larva consisted of a scolex, where suckers and duct-like invaginated segment could be identified at the caudal end. A digitiform coating of homogenous eosinophillic membrane was evident lining the cystic area. A final diagnosis of oral cysticercosis was made. MRI and CT scan were negative which ruled out neurocysticercosis (NCC).

Example four, Venkatramana and colleagues (2013)^[27]: Histopathology of the excised tissue revealed a thin capsule of fibrous connective tissue surrounding a cystic cavity, which contained cysticercosis cellulosae (larval form of Taenia solium). The larva composed of a duct like tubal segments that was lined by a homogeneous membrane. Cyst wall and outer fibrous tissue was infiltrated with numerous inflammatory cells, macrophages and few foreign body type giant cells. Based on these findings, a diagnosis of cysticercosis was made

Example five, Chunduri and colleagues (2013^[2]: Microscopic examination revealed double glycoprotein membrane tissue surrounding a cystic cavity which contained Cysticercus cellulosae. The capsule showed intense inflammatory infiltrate, consisting mainly of lymphocytes and plasma cells. The larva was composed of a scolex, where a sucker could be identified, and a duct-like invaginated segment at the caudal end. No areas of dystrophic calcification were present in the specimen. Based on these findings, a diagnosis of cysticercosis was made.

Example six, Neves Santos and colleagues (2012)^[21]: histological sections revealed the presence of a cystic lesion containing a serrated larva (C. cellulosae) with a cuticle and well-defined areolar and cellular layers as well as a cystic capsule exhibiting predominantly mononuclear inflammation. The final diagnosis was cysticercosis of the tongue.

Example seven, Krishnamoorthy and colleagues (2012)^[14]: A fine-needle aspiration (FNA) was performed. The aspirate was a clear fluid but the report was not conclusive. Hence the lesion was excised under local anesthesia which was a smooth well-encapsulated mass. Hematoxylline and eosin (H/E) stained sections showed a cystic mass containing the cysticercus cellulosae surrounded by dense fibrous capsule infiltrated with inflammatory cells, mainly lymphocytes and plasma cells. The inner aspect of the capsule was a double-layered membrane in which larval form of T. solium were seen. Larva showed the presence of suckers and caudal to it duct-like invagination segment lined by homogenous membrane. No areas of dystrophic calcifications were present in the tissue specimen. The final diagnosis of cysticercosis of the lip was made.

Differential diagnoses for oral cysticercosis

Oral cystucercosis is usually misdiagnosed as a mucocele, sialocyst or a benign tumor of mesenchymal origin such as lipoma, fibroma, hemangioma, lymphangioma, granular cell tumor  ^{[16, 27]}, benign salivary gland neoplasms^[8] and parasitic cysts e.g. hydatid cyst. Stool examination is usually carried out to rule out parasitic cysts ^[28].

Treatment

Oral cysticerci, being usually localized and superficial lesions, are easy to excise and have good prognosis. Simple surgical excision is often all that is required to ensure complete removal of the lesion without any postoperative complications in such cases^[5]. Lesions involving the muscles like the masseter may be treated conservatively with antiparasitic therapy^[18]. Unlike the neurocysticercosis or orbital cysticercosis which are severe in their clinical presentations, the oral cysticercosis are usually well tolerated. However, it is important to exclude the presence of the parasite in other sites through a detailed case study and systematic investigations ^[14]. Praziquantel and albendazole are used to treat cysticercosis, especially in patient with disseminated cysticercosis or where surgical excision is risky or not possible, such as in neurocysticercosis^[4].

Control and prevention

Transmitted via the orofecal route, cysticercosis is potentially eradicable. To prevent and eradicate human cysticercosis supportive measures such as improvement in the sanitary conditions, pork inspection, consumption of boiled water, well washed vegetables, mass education about personal hygiene should be undertaken along with medical treatment (by a registered and approved medical practitioner) which includes larvicidal drugs, corticosteroids, and surgical procedure for removal of the cyst^{[25, 28]}.

The role of the dental clinician?

The illustrations above clearly tell us the critical role that clinicians and especially dentists have in the control  of not only oral cysticercosis but cysticercosis as a Neglected Tropical Disease. The patient diagnosis of oral cysticercosis could act as a “sentinel” and insight to further investigate and control the problem in the family or community at large.

It is clear that oral cysticercosis should be considered in the differential diagnosis of intraoral solitary swellings especially in endemic areas. In endemic countries a lesion can be first referred for a FNA which is cost-effective, quick, and reliable. Expensive investigations, like immunological tests and CT, can be undertaken only in the absence of a definitive pathological diagnosis. As much as the histopathological findings of the excised swelling are diagnostic of the lesion a detailed evaluation should be done to exclude the presence of the parasite at other sites^{[14, 2]}.

References

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