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Year : 2014  |  Volume : 57  |  Issue : 2  |  Page : 314-316
Metachronous malignancies in head and neck region: Report of two cases

Department of Pathology, Mamatha Medical College, Khammam, Andhra Pradesh, India

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Date of Web Publication19-Jun-2014


The development of a second primary cancer after treatment of the first with radiotherapy or chemotherapy is well documented. Multiple metachronous primary cancers are known to occur in an individual, but it is often seen with hematological malignancies of childhood. The prevalence of multiple primary malignancies (MPM) is between 0.73% and 11.7%. The most frequent malignant associations are ovary-colon, ovary-breast, and breast-breast. The possibility of developing a second metachronous cancer 5 years after undergoing treatment of the initial head and neck cancer is approximately 22%. Here, we report two cases of multiple metachronous malignancies in head and neck region. A 46-year-old woman presented with thyroid and salivary gland neoplasms metachronously and another 21-year-old woman with Hodgkin' s Lymphoma, mucoepidermoid carcinoma of salivary Gland, and follicular variant of papillary carcinoma of thyroid.

Keywords: Head and neck region, metachronous, multiple primary malignancies, salivary gland, thyroid

How to cite this article:
Yalavarthi S, Pamu PK, Thoondla M, Gupta S. Metachronous malignancies in head and neck region: Report of two cases. Indian J Pathol Microbiol 2014;57:314-6

How to cite this URL:
Yalavarthi S, Pamu PK, Thoondla M, Gupta S. Metachronous malignancies in head and neck region: Report of two cases. Indian J Pathol Microbiol [serial online] 2014 [cited 2023 Sep 26];57:314-6. Available from:

   Introduction Top

Cancer patients have a 20% higher risk of new primary cancer, in the same organ or in another organ, compared with the general population. [1] Subsequent malignancies can be either synchronous or metachronous. Synchronous cancers are second tumors occurring simultaneously or within 6 months after the first malignancy, while metachronous multiple malignancies are secondary cancers that develop after more than 6 months from first malignancy. [2],[3] Patients with head and neck squamous cell carcinoma are at increased risk for the development of second primary malignancies compared with the general population. [4] Such second primary cancers may be difficult to distinguish from locoregional recurrences. [5] We present two cases of metachronous malignancies in head and neck region.

   Case report Top

The first case was a 46-year-old female patient who presented with painless anterior neck swelling for the last one year. Fine needle aspiration (FNAC) of thyroid revealed features of papillary thyroid carcinoma with papillary structures with oval optically clear nuclei with overlapping and occasional grooves and areas of calcification. Total thyroidectomy with modified radical neck dissection was performed and was confirmed as papillary thyroid carcinoma [Figure 1]. After one year, patient presented with preauricular swelling and FNAC reported as metastasis, since nuclear features of papillary thyroid carcinoma (PTC) were absent and histopathology was suggested, which turned out as basal cell carcinoma of parotid gland with large hyperchromatic oval nuclei without nuclear features of PTC [Figure 1]. The tumor showed infiltration into subcutis. P63 immunohistochemical stain was done to confirm the diagnosis which showed positivity [Figure 1]. The second case was a 21-year-old female patient who presented with multiple cervical lymph nodes. With the help of fine needle aspiration of lymphnodes, CD 15, and CD 30 positivity, the diagnosis of Hodgkin's Lymphoma was made and chemotherapy was given [Figure 2]. After 4 years, she presented with swelling of left parotid and cytologically it reported as mucoepidermoid carcinoma based on the findings of large neoplastic epithelial cells against myxoid background [Figure 3]. Histopathological sections of mucoepidermoid carcinoma exhibited different areas of intermediate squamous and glandular cells with mucin. Alcian blue PAS stain was done for mucin which was positive. After 2 years, she presented with anterior neck swelling and reported as follicular neoplasm of thyroid on cytology. Left hemithyroidectomy was performed and reported as Follicular variant of papillary thyroid carcinoma. CD 19 was positive [Figure 3].
Figure 1: FNA smears of a 46-year-old female showing (a) Papillary carcinoma of thyroid (b) Basal cell adenocarcinoma of parotid (H&E, x400) (c) sections show features of basal cell adenocarcinoma with p63 positivity (H&E, x400)

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Figure 2: (a) FNA smears of lymph node from a 21-year-old female show large Reed Sternberg Cells. Immunohistochemical examination shows (b) CD30 (c) CD15 positivity (H&E, x400)

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Figure 3: (a and b) FNA smears and Sections show features of mucoepidermoid carcinoma of Parotid with different areas of intermediate, squamous, and glandular cells with mucin (H&E, x400) (c) Smears of follicular variant of papillary carcinoma (H&E, X100) (d) CD19 positivity in neoplastic cells (H&E, X100)

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   Discussion Top

Second cancers have become a leading cause of death among long-term cancer survivors. The development of second cancer in cancer survivor is expected but third, or higher order malignancies are rare. Multiple primary malignancies (MPM) are common; in 3-5% of malignant tumors which are most often secondary, triple tumors occur in only 0.5%, quadruple tumors in 0.3% of malignant tumors. [6]

Nearly one hundred years ago, Billroth first reported on synchronous cancers in various organs. About 40 years later, Warren and Gated established the criteria for the diagnosis of multiple primary tumors. According to the criteria, such tumors occurring at different locations must be histologically malignant and anatomically separated by normal mucosa, and one tumor must not be a metastasis of another and the tumor-free interval should be at least 2 years. [5]

The entity of MPM is not very rare. The mechanisms involved in the occurrence of MPMs are not yet elucidated. There are several other reasons for a patient to develop MPM. There may be a genetic predisposition resulting in the cancer family syndrome. The BRCA gene mutation would be one such example. Widespread use of chemotherapeutic agents and radiotherapy might also cause. They may also arise as a result of oncogenic viruses such as HPV and HTLV1 and DNA damaging toxins. They may also arise by chance as successful treatment of one malignancy causes prolongation of survival with the possibility of a second one occurring. [7]

Second Primary Tumors (SPT) may also occur due to the presence of genetic base, especially the multiorgan susceptibility gene, the CHEK2 protein was associated with an increased risk of cancers of breast, colon, kidney, prostate, and thyroid. [8] In some studies, several other cancer sites showed significantly increased risks in both directions, including salivary glands, prostate, breast, kidney, scrotum, brain, and leukemia. [8] Another gene is the PTEN gene with an increased risk of benign and malignant tumors of the breast, thyroid, and endothelium. [8]

Multiple thyroid and salivary gland malignancies are rare and only few reports are available. Literature review was performed to check syndromic and therapy-related etiology for occurrence of thyroid and salivary gland carcinomas.

Online Mendelian Inheritance in Man (OMIM)-based data search is not showing possibility of familial/hereditary cancers involving both thyroid and salivary gland. Approximately 5% of non-Medullary Thyroid Carcinoma (NMTC) is hereditary, occurring as a component of a familial cancer syndrome (familial adenomatous polyposis, Carney's complex) and salivary gland is not involved in these syndromes. Several genetic abnormalities are reported in salivary gland (OMIM 181030; 603641) but Syndromic/familial involvement is not described. However, genetic analysis may provide better understanding of multiple head and neck cancers.

Pubmed-based data search shows rare thyroid involvement as Second Primary after Major Salivary Gland Cancer (Standardized Incidence ratio = 2.66, P < .05).Thyroid cancer and multiple primary tumors in the SEER cancer registries show that patients <40 years of age at diagnosis of thyroid cancer had a 39% increased risk of a second cancer, whereas for older patients the risk was elevated by 6%. Few observers stated that there was small excess in salivary gland, adrenal, and central nervous system (CNS) malignancies, when compared with frequently occurring breast, prostate, kidney, and a radiation treatment-related leukemia. Salivary gland neoplasm may be seen associated with lymphoma including Hodgkin's lymphoma. Similarly, papillary thyroid carcinoma do occur post radiation in Hodgkin's lymphoma. Sequential occurrence of all three malignancies was not seen as reported by us.

To conclude, multiple malignancies involving thyroid and salivary gland are very rare and need to be reported to check genetic or mutational abnormalities along with therapy status. Cytology plays an important role for early detection of secondary malignancies prior to definitive surgical management.

   References Top

1.Soerjomataram I, Coebergh JW. Epidemiology of multiple primary cancers. Methods Mol Biol 2009;471:85-105.  Back to cited text no. 1
2.Suzuki T, Takahashi H, Yao K, Inagi K, Nakayama M, Makoshi T, et al. Multiple primary malignancies in the head and neck: A clinical review of 121 patients. Acta Otolaryngol Suppl 2002;88-92.  Back to cited text no. 2
3.Irimie A, Achimas - Cadariu P, Burz C, Puscas E. Multiple primary malignancies - epidemiological analysis at a single tertiary institution. J Gastrointestin Liver Dis 2010;19:69-73.  Back to cited text no. 3
4.Fletcher H, Wharfe G, Williams E, Hanchard B, Mitchell D. Multiple metachronous malignancies, one patient with three primary malignancies: A case report. J Med Case Rep 2007;1:15.   Back to cited text no. 4
5.Warren S, Gates O. Multiple primary malignant tumors: A survey of the literature and a statistical study. Am J Cancer 1932;16:1358-414.   Back to cited text no. 5
6.Sakashita H, Miyata M, Miyamoto H, Kurumaya H. A case of quadruple cancer, including triple cancers in the head and neck region. J Oral Maxillofac Surg 1996;54:501-5.  Back to cited text no. 6
7.Arpaci E, Tokluoglu S, Yetigyigit T, Alkis N. Multiple primary malignancies - a retrospective analysis at a single center in Turkey. Asian Pac J Cancer Prev 2013;14:769-73.   Back to cited text no. 7
8.Jayaraman S, Balakrishnan S, Rao D. Multiple metachronous malignancies, one patient with three primary malignancies. Indian J Surg 2011;73:377-9.  Back to cited text no. 8

Correspondence Address:
Sushma Yalavarthi
Department of Pathology, Mamatha Medical College, Khammam, Andhra Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.134728

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