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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 7  |  Issue : 2  |  Page : 317-320

Axillary lymphadenopathy in a case of breast carcinoma: Is it always metastatic?


Department of Pathology, Employees' State Insurance Corporation Medical College and PGIMSR, Bengaluru, Karnataka, India

Date of Submission07-Mar-2022
Date of Decision30-Aug-2022
Date of Acceptance01-Sep-2022
Date of Web Publication06-Dec-2022

Correspondence Address:
Panduranga Chikkannaiah
Department of Pathology, Employees' State Insurance Corporation Medical College and PGIMSR, Bengaluru - 560 010, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/bjhs.bjhs_40_22

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  Abstract 


Cancer and tuberculosis are the most common illnesses in the world; however, their coexistence is not uncommon and a challenge for pathologists and clinicians. The instances of mucinous carcinoma and disseminated tuberculosis are exceptional. Here, we present such a rare case of incidentally detected mucinous carcinoma of the breast with disseminated miliary tuberculosis in a 59-year-old female. The pertinent literature is being reviewed.

Keywords: Carcinoma of breast, mucinous carcinoma, tuberculosis, miliary tuberculosis


How to cite this article:
Vijayasarathy PC, Chikkannaiah P, Sajjan NM, Ramalingaiah VB, Venkataramanappa S. Axillary lymphadenopathy in a case of breast carcinoma: Is it always metastatic?. BLDE Univ J Health Sci 2022;7:317-20

How to cite this URL:
Vijayasarathy PC, Chikkannaiah P, Sajjan NM, Ramalingaiah VB, Venkataramanappa S. Axillary lymphadenopathy in a case of breast carcinoma: Is it always metastatic?. BLDE Univ J Health Sci [serial online] 2022 [cited 2023 Jan 28];7:317-20. Available from: https://www.bldeujournalhs.in/text.asp?2022/7/2/317/362834



Cancer and tuberculosis are the most common diseases worldwide, which mimic each other.[1] The coexistence of mucinous carcinoma of the breast and disseminated tuberculosis is infrequent.[2] Mucinous breast carcinoma is a rare subtype of breast carcinoma, representing approximately 1%–7%. The association of mucinous carcinoma of the breast with tuberculosis of the ipsilateral axillary lymph node is extremely rare. Lymphadenopathy in the axilla due to tuberculosis, without cytological examination, can lead to erroneous high staging of the breast cancer. The coexistence of tuberculosis infection and malignant lesions is not just of academic interest but is of great clinical importance in the course of treatment. The occurrence of mucinous or colloid carcinoma of the breast with tuberculosis of the ipsilateral axillary lymph node synchronously is a rare phenomenon.[2] This case is being reported to highlight the prognostic implications of identifying the two entities separately.


  Case Report Top


A 59-year-old female patient presented to the emergency department with complaints of altered sensorium, irrelevant speech, and giddiness for 4 days. Patient's attendant gave a history of generalized weakness, repeated episodes of vomiting, weight loss, and decreased appetite for 3 months. Family history and personal history were not significant. On general physical examination, the patient was moderately built and poorly nourished. The patient was drowsy, and she was not able to identify the family members. She was afebrile, pulse rate was 90 beats/min, blood pressure was 84/64 mm/Hg, and respiratory rate was 20 cycles/min. Pallor and koilonychia were present. On systemic examination, she had an MMSE score of 5/30 with intact motor and sensory functions. Other systemic examinations were within the normal limits. Routine blood and biochemical investigations were within the normal limits except for anemia (hemoglobin of 10.7%) and hyponatremia (Se Na+-125 mEq/L). cerebrospinal fluid (CSF) analysis showed 250 cells/mm3 with lymphocytic predominance (90%), CSF-lactate dehydrogenase: 469, CSF-glucose: 38 mg/dL, and CSF-protein: >6000 mg/dL. Ziehl–Neelsen (ZN) stain and Gram's stain were negative. She underwent hyponatremia correction and after which symptoms such as altered sensorium, irrelevant speech, and giddiness were improved.

The patient was evaluated previously at a local hospital for her abdominal complaints. Ultrasonography of the abdomen showed multiple discrete lymph nodes measuring 10–20 mm. On further evaluation with a computed tomography scan of the abdomen showed hepatomegaly and splenomegaly with 17 cm and 13 cm span, respectively. Discretely enlarged lymph nodes were noted in celiac, peripancreatic, paracaval, aortocaval, obturator, iliac, and inguinal group of lymph nodes; each measuring about 10–20 mm in the short axis [Figure 1]c. With the above findings, a clinical suspicion of abdominal lymphoma was made and referred to oncology center; however, the patient had not sought any medical help in this regard. Chest X-ray of the patient showed multiple tiny nodular opacities [Figure 1]b.
Figure 1: (a) Lump in the left breast (red arrow head) (b) Chest X-ray showing miliary tuberculosis (c) CT abdomen showing multiple enlarged lymph nodes. CT = Computed tomography

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On detailed physical examination, a hard breast lump was noted in the left upper and inner quadrant measuring 2 cm × 2 cm, [Figure 1]a which was fixed, nonmobile, and nontender; associated axillary lymph nodes were palpable and subcentimetric. Cervical and inguinal lymph nodes were not palpable. The patient had not noticed the lump before. Fine-needle aspiration cytology (FNAC) from the breast lump yielded mucinous material. Microscopy of the lesion showed cellular smears consisting mostly of neoplastic ductal cells floating in abundant pools of mucin. The neoplastic ductal cells showed slight pleomorphism, with few having prominent nucleoli [Figure 2]a and [Figure 2]b. With the above findings, a possible diagnosis of mucinous carcinoma of the left breast was made. The FNAC of the axillary lymph node yielded only hemorrhagic material. Trucut biopsy was performed for the left-sided breast lump, and excision biopsy was done for the lymph node. Biopsy from the left breast lump showed tumor cells arranged in nests, and lobules with individual tumor cells exhibited increased N: C ratio and vesicular nuclei with scant to moderate vacuolated cytoplasm. These tumor cells were found floating in the mucinous material. As mucin constituted more than 90%, a diagnosis of pure mucinous carcinoma of the breast was made [Figure 2]c and [Figure 2]d. Excision biopsy of the lymph node showed epithelioid cell aggregates, multinucleated giant cells, lymphocytes, and caseous necrosis, indicating a necrotizing granulomatous inflammation [Figure 2]e and [Figure 2]f. However, ZN stain done for acid-fast bacilli was negative. The extracellular mucin around the tumor cells was positive for mucicarmine stain, i.e., mucin stained in deep rose color [Figure 2]g and [Figure 2]h. Immunohistochemistry performed on the trucut biopsy of the breast lump was negative for estrogen receptor, progesterone receptor, and HER2/neu receptor [Figure 3]a,[Figure 3]b,[Figure 3]c. Ki-67 was <14% [Figure 3]d.
Figure 2: (a) Cytology slide showing ductal cells in pools of mucin (Leishman stain, ×10), (b) Higher magnification of the same (×40), (c) Histopathology slide showing ductal cells in pools of mucin (red star) (H and E, ×10), (d) Higher magnification of the same (×40), (e) Histopathology slide showing caseating necrotizing granulomatous lymphadenitis (red arrow head showing necrosis) (H and E, ×10), (f) Caseating granuloma with Langhans giant cell (black arrow head) (H and E, ×40), (g) Mucicarmine stain showing positivity for mucin (black star) (×10), (h) Higher magnification of the same (Black star) (×40)

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Figure 3: Immunohistochemistry slides showing ER (a: anti-ER, ×40), PR (b: anti-PR, ×40), and HER2/neu (c: anti-HER2/neu, ×40) negative, respectively. (d) Immunohistochemistry slide showing Ki-67 <14% (red arrow head) (anti-Ki 67, ×40)

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Magnetic resonance imaging of the brain showed moderate hydrocephalus with excessive leptomeningeal thickening and enhancement with supra- and infratentorial tubercles. The positron emission tomography showed 2.5 cm × 2.2 cm lobulated mass in the upper and inner quadrants of the left breast with enlarged bilateral axillary, left internal mammary, and mediastinal, abdomino-pelvic, and retroperitoneal lymph nodes. Extensive pulmonary miliary nodules were noted suggestive of the miliary lesion. The tracheal aspirate sent for reverse transcription–polymerase chain reaction (GeneXpert) showed trace positivity for Mycobacterium tuberculosis with indeterminate resistance for rifampicin, suggesting a disseminated tubercular infection.

With the above findings, a final diagnosis of mucinous carcinoma of the left breast (Capella Type A) with disseminated miliary tuberculosis was made.

As her general condition was poor and she had disseminated miliary tuberculosis, including tubercular meningitis, a call was taken to wait till her general condition improves over the treatment of her malignant lesion. Hence, she was started on antitubercular treatment, and mastectomy was planned later. Now, the patient is on regular follow-up and is responding to antitubercular treatment.


  Discussion Top


Tuberculosis and cancer are the two most common diseases which have a high degree of mortality in developing countries.[3] Rarely, both these lesions can occur together. Cancer and tuberculosis can occur in different forms, i.e., cancer may develop in the background of tuberculosis or tuberculosis may coexist with the cancer either in the same organ or in their draining lymph nodes. If tubercular lymphadenopathy occurs in the draining lymph node, it may lead to erroneous higher staging. This causes difficulty in planning the treatment protocol.

Mucinous carcinoma is a rare type of breast cancer, which is characterized by the presence of large amounts of extracellular mucin. It is seen predominantly in women of postmenopausal age.[4] These tumors have varied names such as colloid carcinoma, mucinous carcinoma, gelatinous carcinoma, mucoid carcinoma, and mucinous adenocarcinoma of the breast.[5] Pure mucinous carcinoma is defined when the carcinoma is made up of at least 90% of mucin (intracellular or extracellular). Mixed mucinous carcinoma is composed of <90% of mucin with morphological architectures such as lobular or ductal breast cancer.[6] Per se, mucinous carcinoma of the breast is considered a less aggressive tumor with the lesion being mostly confined to the parenchyma of the breast. Metastasis of this tumor to the draining axillary lymph nodes and distant metastasis, in itself are considered a rare phenomenon.[4] A metastatic disease in the lymph nodes is considered one of the most important prognostic factors for breast cancer; high degree of caution needs to be exercised in the preliminary clinical staging of mucinous breast carcinoma. FNAC can quickly help in such a situation.[4]

Tubercular lymphadenitis is the most common form of extrapulmonary tuberculosis. However, disseminated tuberculosis is a fatal condition with high morbidity and mortality. Dissemination of M. tuberculosis may occur due to progression of the primary infection or reactivation of a latent focus with subsequent lymphohematogenous spread. The miliary pattern is a common finding on chest radiography that has an important role in the early detection of the disease.[7]

The breast and the axilla are inseparable and are clinically considered a single entity by the clinicians. The most common cause of enlarged lymph nodes in the axillary region in a case of carcinoma breast is metastasis. However, a few other diseases causing axillary lymphadenopathy can overlap with metastasis, such as sarcoidosis, foreign-body reaction, cat-scratch disease, brucellosis, lymphoma, and acquired immunodeficiency syndrome.[8] Thus, a careful detection and histopathological examination are essential to differentiate it from the metastasis.

The association between tuberculosis and cancer has been found in most organs. In a large series by Kaplan et al.[9]in 58,245 cases found that association of tuberculosis and carcinoma of the breast is the third most common finding, preceded by lung carcinoma and head and neck carcinomas.[9] Huang et al.[10] observed in a series of 2187 cases, 54 patients of gastric cancer developed tuberculosis. Both of these studies indicate that immunosuppression by the cancer is the primary cause for tuberculosis.[10]

In a meta-analysis on tuberculosis and carcinoma of the breast by Akbulut et al,[8] the patients age ranged from 28 to 81 years (mean of 52.9 ± 14.7 years). The right breast was seen to be more commonly involved than the left breast. Axillary tuberculosis was detected in all cases. Six cases showed concurrent tuberculosis and metastasis in the lymph node. Their analysis showed infiltrating ductal carcinoma of the breast as the most common histopathological subtype with axillary tuberculosis. Only case of mucinous carcinoma has been identified in the series indicating the rarity of the association.[8]

The coexistence of breast cancer and tuberculosis leads to a complex diagnosis and treatment. Due to the lack of literature reports, no consensus is available for the initiation and duration of antitubercular treatment in such cases. The association of antitubercular treatment with chemotherapy is still not established.


  Conclusion Top


To conclude, coexistence of mucinous carcinoma of the breast and axillary tuberculosis is rare.[11] Caution must be executed in assessing the axillary lymphadenopathy in the carcinoma of breast cases to avoid over staging. As there are no clear guidelines for antitubercular treatment in cases of breast carcinoma, it should be judged on a case-by-case basis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Xiang Y, Huang C, He Y, Zhang Q. Cancer or tuberculosis: A comprehensive review of the clinical and imaging features in diagnosis of the confusing mass. Front Oncol 2021;11:644150.  Back to cited text no. 1
    
2.
Falagas ME, Kouranos VD, Athanassa Z, Kopterides P. Tuberculosis and malignancy. QJM 2010;103:461-87.  Back to cited text no. 2
    
3.
Jagtap SV, Naniwadekar RG, Jokhi CD, Jagtap SS. Invasive breast carcinoma with axillary tuberculous lymphadenitis. J Clin Diagn Res 2018P; 1:12.  Back to cited text no. 3
    
4.
Marrazzo E, Frusone F, Milana F, Sagona A, Gatzemeier W, Barbieri E, et al. Mucinous breast cancer: A narrative review of the literature and a retrospective tertiary single-centre analysis. Breast 2020;49:87-92.  Back to cited text no. 4
    
5.
LaBoy C, Siziopikou KP. Mucinous. PathologyOutlines.com website. Available from: https://www.pathologyoutlines.com/topic/breastmalignantmucinous.html. [Last accessed on 2021 Dec 17].  Back to cited text no. 5
    
6.
Chikkannaiah P, Thangngeo D, Guruprasad C, Venkataramanappa S. Clinicopathological study of mucinous carcinoma of breast with emphasis on cytological features: A study at tertiary care teaching hospital of South India. J Lab Physicians 2020;12:68-75.  Back to cited text no. 6
    
7.
Khan FY. Review of literature on disseminated tuberculosis with emphasis on the focused diagnostic workup. J Family Community Med 2019;26:83-91.  Back to cited text no. 7
    
8.
Akbulut S, Sogutcu N, Yagmur Y. Coexistence of breast cancer and tuberculosis in axillary lymph nodes: A case report and literature review. Breast Cancer Res Treat 2011;130:1037-42.  Back to cited text no. 8
    
9.
Kaplan MH, Armstrong D, Rosen P. Tuberculosis complicating neoplastic disease. A review of 201 cases. Cancer 1974;33:850-8.  Back to cited text no. 9
    
10.
Huang SF, Li CP, Feng JY, Chao Y, Su WJ. Increased risk of tuberculosis after gastrectomy and chemotherapy in gastric cancer: A 7-year cohort study. Gastric Cancer 2011;14:257-65.  Back to cited text no. 10
    
11.
Chamberlin K, Orfanos S, Mukherjee A, Moy E, Koganti M, Khan W. A case of disseminated tuberculosis mimicking metastatic cancer. Respir Med Case Rep 2018;25:239-41.  Back to cited text no. 11
    


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