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Year : 2011  |  Volume : 54  |  Issue : 2  |  Page : 388-390
Oral diffuse B-cell non-Hodgkin's lymphoma associated to Gorlin-Goltz syndrome: A case report with one year follow-up

1 Department of Pathology, Estácio de Sá University, Goiânia/GO and Brasília/DF-Brazil and Department of Oral Pathology, Scholl of Dentistry, Paulista University, Goiânia/GO, Brazil
2 Private practice, Goiânia/GO, Brazil
3 Clinical Oncology, Araújo Jorge Hospital, Goiânia/GO, Brazil
4 Department of Oral Pathology, Scholl of Dentistry, Paulista University, Goiânia/GO, Brazil

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Date of Web Publication27-May-2011


Nevoid cell carcinoma syndrome or Gorlin-Goltz syndrome is an autosomal dominant disorder characterized by multiple basal cell carcinoma, multiple keratocyst tumors, and skeletal anomalies. The Gorlin-Goltz syndrome has been associated with numerous benign and malignant neoplasms. The authors describe a case of Gorlin-Goltz syndrome in association with non-Hodgkin's lymphoma. To the best of our knowledge, this is the second case described in the English literature.

Keywords: Gorlin-Goltz syndrome, non-Hodgkin′s lymphoma, neoplasms

How to cite this article:
Pereira CM, Lopes AM, Meneghini AJ, Silva AF, Botelho Td. Oral diffuse B-cell non-Hodgkin's lymphoma associated to Gorlin-Goltz syndrome: A case report with one year follow-up. Indian J Pathol Microbiol 2011;54:388-90

How to cite this URL:
Pereira CM, Lopes AM, Meneghini AJ, Silva AF, Botelho Td. Oral diffuse B-cell non-Hodgkin's lymphoma associated to Gorlin-Goltz syndrome: A case report with one year follow-up. Indian J Pathol Microbiol [serial online] 2011 [cited 2020 Sep 24];54:388-90. Available from: http://www.ijpmonline.org/text.asp?2011/54/2/388/81649

   Introduction Top

Nevoid basal cell carcinoma syndrome (NBCCS) was first described by Jarisch and White in 1894, but it was not widely recognized until Gorlin and Goltz delineated the syndrome in 1960 as cited by Gorlin. [1] NBCCS is a autosomal dominant disease characterized by the predisposition to develop basal cell carcinoma of the skin, palmar and plantar dyskeratosis, multiple odontogenic keratocyst tumors, skeletal malformations as abnormalities of the ribs and vertebrae, and calcification of the faux cerebri. [2]

Several neoplasms have been reported in association with NBCCS, including medulloblastoma, craniopharyngioma, meningioma, astrocytoma, oligodendroglioma, ovarian fibroma, ovarian fibrosarcoma, cardiac fibroma, fetal rhabdomyoma, rhabdomyosarcoma, ameloblastoma, squamous cell carcinoma, seminoma, melanoma, leiomyoma, thyroid adenoma, adenocarcinoma of the rectum, benign mesenchymoma, adrenal cortical adenoma, Hodgkin's disease, and non-Hodgkin's lymphoma. [3] The non-Hodgkin's lymphoma (NHL) associated with NBCCS is very rare and we did not find any similar clinical case reported in the English literature. The purpose of this report is to describe the second case of NHL associated with NBCCS.

   Case Report Top

A 24-year-old man was referred to the oral diagnosis section with the complaint of a rapidly growing painful mass on the right lower gingiva lasting three months. There was no history to suggest a similar case in his family. Clinical examination showed facial asymmetry on the right side [Figure 1] and submandibular and submental lymphadenomegaly. Intraorally, there was an expansile mass in the right maxillary and mandibular regions and ulcerated exophytic lesion over the hard palate [Figure 1]. Panoramic radiograph showed multilocular radiolucent lesion with regular borders, causing tooth displacement in the right maxillary and mandibular regions [Figure 2]. Based on the radiographic findings, the diagnosis of multiple keratocyst tumors was postulated. Incisional biopsy of right mental and maxillary regions was performed.
Figure 1: (Left) Facial asymmetry on the right side. Clinical examination demonstrated the expansile mass in the right maxillary (Right above) and mandibular regions (Right below)

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Figure 2: (Below) The radiographic examination showed multilocular radiolucent borderline lesion, causing tooth deviation in the right maxillary and mandibular regions. (Above) Computed tomography of the face showed cystic expansile lesion in mandible and maxilla with extension into the right parapharyngeal space, base of the skull. (Right above) Calcification of cerebral sickle was seen

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The histopathologic examination showed fibrous connective tissue contoured by thin keratinized stratified squamous epithelium with about eight layers of cells, with a corrugated surface. The basal cell layer was in a palisaded arrangement with a tendency of the nuclei being polarized away from basal membrane, which confirmed the clinical diagnosis. Because of the severe trismus, the patient was referred to the department of head and neck to assess the palatal lesion. Computed tomography scan showed multiple cystic expansile lesions in the mandible and maxilla with extension to the right parapharyngeal space extending to the base of the skull. Calcification of cerebral sickle was reported. All these features suggest a diagnosis of Gorlin-Goltz syndrome [Figure 2]. A fresh biopsy of the right parapharyngeal and palatal region histopathologically evidenced the presence of small hyperchromatic cells with pleomorphism in shape and size, suggesting a pattern of "starry sky." An immunohistochemical analysis showed a positive reaction for CD-20, but not for Pancytokeratin, CD-43 or CD-56, establishing the diagnosis of diffuse B-cell NHL [Figure 3].
Figure 3: Photomicrograph showing small hyperchromatic cells with pleomorphism and "starry sky" pattern. (inset) Diffuse positivity to CD-20

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The patient has undergone chemotherapy with CHOP regime. After five cycles of chemotherapy, the patient received a course of radiotherapy as a concomitant treatment. The patient's condition gradually deteriorated over the 15 following months, and he still has severe pain, trismus, and weight loss [Figure 4]. The tumor is at the IVB stage, with evidence of involvement of inguinal nodes and is nonresponsive to treatment.
Figure 4: After 15 months, the patient still has trismus

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   Discussion Top

Gorlin-Goltz syndrome (NBCCS) is an autosomal dominant disorder with a high penetrance and variable expressivity. It is caused by mutations in the patched tumor suppressor gene (PTCH), mapped to chromosome 9q22.3. The PCTH gene product is part of a receptor for the protein called Sonic Hedgehog (SHH), which is involved in embryonic development. More recent investigations reveal the role of the Hh pathway in cell cycle regulation in adults. [4] The NBCCS prevalence has been variously estimated from 1 in 57,000 to 1 in 164,000, but there is now a general agreement that the prevalence is about 1 per 60,000. NBCCS probably arises in all ethnic groups, but most reports have been of whites. Males and females are equally affected, the clinical features of NBCCS arising in the first, second, or third decade. [5]

There are two groups of diagnostic criteria: major criteria and minor criteria. The "major criteria" are multiple (>2) basal cell carcinomas or one basal cell carcinoma under the age of 30 years or >10 basal cell nevi, odontogenic keratocyst tumors (proven on histology), palmar or plantar pits (3 or more), ectopic calcification, faux calcification, [6] and positive family history of NBCCS. [2] The "minor criteria" are congenital skeletal abnormality (bifid, fused, splayed or missing ribs, or fused vertebrae), occipitofrontal circumference more than 97th percentile, cardiac or ovarian fibroma, medulloblastoma, lymphomesenteric cysts, and congenital malformations (cleft lip or palate, polydactylism, or eye anomaly-cataract, coloboma, microphthalmia). The diagnosis of Gorlin-Goltz syndrome can be made when two major or one major and two minor criteria are found. [2]

The prognosis for the patient with lymphoma is determined by the type of lymphoma, its stage, and other prognostic factors. For instance, in diffuse large B-cell NHL the patient's prognostic score can be assessed using the International Prognostic Index, a calculation based on age, performance status, stage, extranodal spread, and lactate dehydrogenase level. Many of the contributory tests are outside the remit of this guideline. However, there are a number of prognostic indicators that must be assessed by immunohistochemistry or molecular genetic analysis. [3],[6] Not the least of these is the expression of BCL2 in diffuse large B-cell lymphoma, the presence of which implies a poorer prognosis than for those tumors that are BCL2 negative. Diffuse large B-cell lymphoma can no longer be regarded as a single disease, because the prognosis is dependent on its germinal center or nongerminal center phenotype, site of origin, association with low-grade disease, presence of t (14;18), expression of BCL2 and mutation of TP53.[6],[7] Decisions about a patient's therapy will increasingly depend on the analysis of these and other markers. Consequently, it is essential that provision is made for these analyses in the future, particularly given the rapid progression in microarray technology that will undoubtedly identify novel genes contributing to diagnosis and prognosis. [8]

One of the most common sites of the extranodal NHL is the head and neck followed by Waldeyer's ring, in descending order of incidence by the oral cavity, thyroid gland, paranasal sinus, nasal cavity, and larynx. NHLs of the parapharyngeal space are rare. [9] It is postulated that the gene for NBCCS may act as a tumor suppressor gene perhaps for many types of cell lines and may explain the diversity of the tumors. [3] This case report is the second one studied relating a patient with NBCCS in association with NHL. There is evidence that mutations in PTCH account for the development of odontogenic keratocyst tumors as well as the tumors associated with NBCCS. NHL should now be included among the malignancies associated with NBCCS.

   References Top

1.Gorlin RJ. Nevoid basal cell carcinoma syndrome. Medicine 1987;66:98-113.  Back to cited text no. 1
2.Kannan KS, Sundharam SB, Manikandan R. Nevoid basal cell carcinoma syndrome. Indian J Dent Res 2006;17:50-3.  Back to cited text no. 2
[PUBMED]  Medknow Journal  
3.Schulz-Butulis BA, Gilson R, Farley M, Keeling JH. Nevoid basal cell carcinoma syndrome and non-Hodgkin's lymphoma. Cutis 2000;66:35-8.  Back to cited text no. 3
4.Kulkarni P, Brashear R, MD, Chuang T. Nevoid basal cell carcinoma syndrome in a person with dark skin. J Am Acad Dermatol 2003;49:332-5.  Back to cited text no. 4
5.Ljubenovié M, Ljubenovié D, Binié I, Jovanovié D, Stanojevié M. Gorlin-Goltz syndrome. Acta Dermatoven APA 2007;16:166-9.  Back to cited text no. 5
6.Gascoyne RD, Adomat SA, Krajewski S, Krajewska M, Horsman DE, Tolcher AW, et al. Prognostic significance of Bcl-2 protein expression and Bcl-2 gene rearrangement in diffuse aggressive non-Hodgkin's lymphoma. Blood 1997;90:244-51.  Back to cited text no. 6
7.Mitchell G, Farndon PA, Brayden P, Murday VA, Eeles RA. Genetic predisposition to cancer: The consequences of a delayed diagnosis of Gorlin syndrome. Clin Oncol 2005;17:650-4.  Back to cited text no. 7
8.Weisenburger DD, Gascoyne RD, Bierman PJ, Shenkier T, Horsman DE, Lynch JC, et al. Clinical significance of the t(14;18) and BCL2 over expression in follicular large cell lymphoma. Leuk Lymph 2000;36:513-23.  Back to cited text no. 8
9.Kayhan FT, Ökul N. Case report: Extranodal non-Hodgkin's lymphoma of the parapharyngeal space. Auris Nasus Larynx 1999;26:201-5.  Back to cited text no. 9

Correspondence Address:
Cláudio M Pereira
Faculdade de Odontologia da Universidade Paulista, Campus Flamboyant, Patologia Oral -Diagnóstico Oral, Rodovia BR, 153, Km 503, Fazenda Botafogo - CEP: 74845-090, Goiania/GO
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.81649

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

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