Nodular Sclerosing Hodgkin's Lymphoma Presenting with a Pseudo-Breast Mass Extending from a Necrotizing Granulomatous Mediastinal Tumor

Abstract

Nodular sclerosing Hodgkin's lymphoma commonly presents with a mediastinal mass, but it rarely compresses or invades mediastinal structures or the anterior chest wall. Histologically, it can cause necrotizing granulomatous inflammation. A woman with a right breast mass extending from an asymptomatic large mediastinal mass selectively compressing the trachea is presented. A computed tomography-guided core needle biopsy from the anterior chest wall mass revealed necrotizing granulomatous inflammation. Finally, the diagnosis of nodular sclerosing Hodgkin's lymphoma was made by incisional biopsy. Clinical suspicion of nodular sclerosing Hodgkin's lymphoma is crucial since an adequate tissue diagnosis is needed when the initial less invasive diagnostic testing is inconclusive.

Introduction

Nodular sclerosing Hodgkin's lymphoma commonly presents with a mediastinal mass that typically does not compress mediastinal structures or invade the anterior chest wall. Histological findings are crucial for diagnosis since Hodgkin's lymphoma may mimic other diseases. We report a case of a woman presenting with a right breast mass extending from an asymptomatic large mediastinal tumor selectively compressing the trachea. A computed tomography (CT)-guided core needle biopsy from the anterior chest wall mass revealed necrotizing granulomatous inflammation. However, incisional biopsy revealed nodular sclerosing Hodgkin's lymphoma.

Case Report

A 42-year-old healthy Thai woman presented with a right breast mass present for 2 months. She discovered a painless mass on her right breast from self-breast examination. The mass was initially small but rapidly enlarged over one month. She denied a history of previous breast mass, nipple discharge, respiratory symptoms, fever, or constitutional symptoms. Her younger sister was recently diagnosed with an early stage breast cancer at age 30. She noted generalized pruritus with no rash. Her last mammogram, performed 10 years ago, was normal. Physical examination revealed a fixed, firm, painless 5 cm mass at the upper inner quadrant of the right breast. There was no warmth, erythema, ecchymosis, skin retraction overlying the mass, nipple retraction, or discharge. There was a movable, rubbery, painless 1 cm right anterior cervical lymph node, but no other adenopathy was found. The lung sounds were clear. She had no signs of upper airway obstruction. Oxygen saturation was 100% on ambient air. Liver and spleen were not palpable. The remainder of the examination was unremarkable.

Mammography showed fibrotic changes without an intrinsic breast mass. A Fine Needle Aspiration (FNA) revealed that not enough cells were obtained because the mass was “too fibrotic.” Chest X-ray showed a bulky mediastinal mass encasing the trachea (Figure 1). Chest CT scan demonstrated an infiltrating necrotic soft tissue mass 10 cm by 12.5 cm by 7.2 cm in the mediastinum. It compressed the trachea, narrowed the antero-posterior dimension of the carina to 2 mm, encased the aortic branch vessels, and extended into the anterior mediastinum and through the anterior chest wall. The overlying right breast tissue was unremarkable (Figures 2, 3, and 4). A CT-guided core needle biopsy from the anterior chest wall mass showed necrotizing “granulomatous” inflammation which was negative for acid fast bacilli and fungi. Concern about the possibility of a graulomatous infection prompted referral to an infectious disease clinic. A CBC revealed: hemoglobin of 10.6 g/dl, MCV of 87.1 fL, WBC of 4,500 cells/µL, neutrophils of 82%, lymphocytes of 4%, monocytes of 12%, eosinophils of 2%, and platelets of 425,000 cells/µL. Abnormal tests included elevated serum alkaline phosphatase of 77, lactate dehydrogenase of 267 IU/L, erythrocyte sedimentation rate of 52 mm/hr, and C-reactive protein of 36.8 mg/L. Serum calcium and albumin were 8.2 mg/dL and 2.8 g/dL, respectively. Liver function, serum electrolytes, urinalysis, and angiotensin converting enzyme level were normal. HBsAg, HBsAb, HIV 1 and 2, and PPD skin test were negative.

Figure 1.

Chest X-ray PA upright shows a bulky mediastinal mass encasing the trachea. The dashed lines show the widest part of each hemi-mediastinum. Summation of both dashed lines is the widest mediastinal diameter (WMD). The solid line shows the internal thoracic diameter (ITD) at T5/6 intervertebral disc space. The ratio between the WMD and ITD is greater than 0.33 in this chest X-ray which indicates a bulky mediastinal mass.

Figure 2.

Chest CT scan with IV contrast in transverse section shows a large infiltrative mass 10 cm by 12.5 cm by 7.2 cm in the anterior, middle, and posterior mediastinum invading the right anterior chest wall and causing significant antero-posterior compression of the trachea with a residual tracheal lumen at carinal level of 2 mm. The overlying right breast tissue was grossly unremarkable. The lungs were otherwise clear.

Figures 3 and 4. Chest CT scan in coronal section shows the bulky mediastinal mass encasing the aortic branch vessels without compression of those vessels.

Because of a potential upper airway obstruction, she was admitted for close observation, and underwent an incisional biopsy which revealed a mediastinal mass invading the chest wall without breast involvement. Pathology examination showed Reed-Sternberg (RS) cells. Immunoperoxidase stains were positive for atypical large cells CD15, CD30, MUM1, and bcl-2 and they were negative for CD3, CD20. Abdominal and pelvic CT scans did not reveal tumor masses. She was diagnosed with early-stage II B nodular sclerosing Hodgkin's lymphoma. She responded well to chemotherapy, and one week after the first cycle of chemotherapy, the right breast mass and the right anterior cervical lymph node disappeared. After the fourth cycle of chemotherapy, positron-emission tomographic (PET) scan was consistent with complete response. Pulmonary function tests showed borderline lung volumes suggesting early restriction, no significant expiratory air flow obstruction, and a volume related reduction in diffusing capacity. She received doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine (ABVD) for 6 cycles, and was treated with mediastinal radiation therapy. At 22 months of follow-up, there is no evidence of disease recurrence.

Discussion

Our patient demonstrated an uncommon manifestation of mediastinal Hodgkin's lymphoma; an initial presentation with an anterior chest wall mass and severe extrinsic compression of the trachea without symptoms of upper airway compression (Figures 2, 3 and 4). The atypical imaging studies along with the granulomatous inflammation on core biopsy created a diagnostic dilemma. Hodgkin's lymphoma is a highly curable disease; however, atypical presentations may mimic other diseases. Often there are no clues from history, physical examination, or imaging studies to differentiate Hodgkin's lymphoma from other diseases causing mediastnal masses. Moreover, histological workup by CT-guided core needle biopsy may be nondiagnostic. Therefore, it is important to be vigilant in pursuing further workup if an initial biopsy of a mediastinal mass only reveals granulomatous changes. We report this case to illustrate a unique presentation of a highly curable disease, and stress the need to pursue a histologic diagnosis.

Figure 3.

Figure 4.

Given a presentation with a breast mass and a history of early breast cancer in our patient's sister, the initial concern of breast cancer was raised. However, chest CT scan demonstrated a large mediastinal mass extending into the anterior mediastinum, through the anterior chest wall, but not into the right breast tissue. Tumors involving the anterior chest wall are uncommon.^1,2 Most often these lesions are malignant, resulting from metastatic bone tumors, plasma cell dyscrasias, or lymphomas.^3–5 Hodgkin's lymphoma spreads contiguously and has a predisposition to favor the lymph nodes in the anterior and superior mediastinum; presenting as an anterior chest wall mass is extremely rare.^3,6 Our patient noted a rapidly growing breast mass, but further investigation revealed it to be a direct extension of her mediastinal lymphoma.

There are several etiologies of a mediastinal mass (Table 1).⁷ In a middle-aged adult, most primary mediastinal tumors are lymphomas; 60% Hodgkin's lymphoma (most commonly nodular sclerosing)^5,8 and 20% Non-Hodgkin's lymphoma.⁹ Symptoms and signs of mediastinal lymphoma depend on the size, location, and rate of progression of the tumor as well as the patient's comorbid conditions.¹⁰ Presentations vary from an absence of symptoms to emergent life-threatening upper airway obstruction. However, a compressive effect on mediastinal structures is rare. While cases of Hodgkin's lymphoma compressing the great vessels have been reported,^11,12 airway compression from Hodgkin's lymphoma is very rare.^13–16 The incidence of tracheobronchial abnormalties from Hodgkin's lymphoma is uncertain,¹³ but one case series reported that severe airway obstruction is a presenting feature of only 2.4% of mediastinal Hodgkin's lymphomas.¹⁴

Table 1.

Common etiologies of the anterior mediastinal mass in adult⁷

	Incidence	Common age groups / Gender	Clinical manifestations
Thymoma	The most common primary tumor of the anterior mediastinum. Rare in children and adolescents	>40 years / Male = female	Mostly asymptomatic 1/3 chest pain, cough, dyspnea, and/or other symptoms related to compression or invasion of adjacent structures. Up to 1/2 suffer from parathymic syndromes (30–50% myasthenia gravis, 10% hypogammaglobulinemia, and 5% pure red cell aplasia)
Hodgkin's lymphoma	The most common mediastinal lymphoma. Nodular sclerosing Hodgkin's lymphoma is the most common.	Bimodal age distribution / Male = Female (Nodular sclerosing: Female = 2*Male) Mediastinal involvement are younger than without mediastinal disease.	Cervical or supraclavicular lymphadenopathy Most mediastinal lymphomas do not cause symptoms and are discovered incidentally on chest radiographs. Patients may experience chest pain, cough, wheezing, and/or dysphagia due to invasion of or mass effect on mediastinal structures. Superior vena cava (SVC) syndrome and chest wall invasion are uncommon.
Non-Hodgkin's lymphoma	Large B-cell lymphoma and lymphoblastic lymphoma primarily involve the anterior mediastinum.	All age groups with a median age of 55 / Male : Female = 1.4:1	85% presents with advanced disease, constitutional symptoms, generalized lymphadenopathy, and/or extensive extranodal disease at diagnosis.
Large B-cell lymphoma		A median age of 26 years, children / Female	Subacutely, occasionally as oncologic emergencies, with signs and symptoms of a rapidly enlarging mediastinal mass that often directly invades the SVC, airway, chest wall, or adjacent structures.
Lymphoblastic lymphoma		1st – 2nd decades / Male	Rapidly enlarging SVC syndrome
Mediastinal germ cell tumors	10–15% of adult anterior mediastinal tumors.	A mean age of 27 years
Teratomas	60–70% of mediastinal germ cell tumor	Male = Female >90% of malignant germ cell tumors occur in male.	Mature teratoma usually asymptomatic, but large tumors may cause chest pain, dyspnea, cough, or other symptoms of compression.
Seminomas	40% of malignant germ cell tumor	Third and fourth decades of life / White men	Usually symptomatic. 10% may have elevated β-HCG
Nonseminomatous malignant germ cell	Includes embryonal cell carcinoma, endodermal sinus tumor, choriocarcinoma, or mixed germ cell tumors	Young adult / Male	Frequently positive LDH, AFP, and β-HCG Associated with hematologic malignancy. 20% have Klinefelter's syndrome.
Mediastinal goiter	10% of mediastinal masses. 20% of cervical goiter descends into thorax. Primary intrathoracic goiters without a cervical part are very rare.	Women	Asymptomatic with a palpable cervical goiter Occasionally causes compressive symptoms or pain.

Our patient's lymphoma selectively compressed her trachea but caused no respiratory symptoms. Mandell, et al, showed that the patients with nodular sclerosing Hodgkin's lymphoma presenting with a mediastinal mass compressing greater than 33% of the trachea had respiratory symptoms, difficulty in intubation, or abnormal pulmonary function.^13,17 Thus, our patient was unique in that despite the significant airway compression she not only denied dyspnea at rest but was able to participate in strenuous exercise without difficulty. Nevertheless upper airway obstruction is unpredictable, and even in the absence of symptoms and signs careful respiratory monitoring is crucial.

Apart from diagnostic CT scans of chest, abdomen, and pelvis, PET scan is recommended for initial staging of patients with lymphoma. It is also used for evaluating residual masses at the end of treatment.¹⁸ However, PET scan cannot be used to diagnose malignancy as sites of infection or inflammation can also display increased uptake of the radioactive tracer.¹⁹ Histological diagnosis is warranted to rule out malignancy in patients presenting with a mediastinal mass invading the anterior chest wall. Our patient did not have a PET scan as part of her initial staging because of lack of insurance.

An additional challenge in this case was the result of the initial core biopsy demonstrating granulomatous inflammation. While histologic diagnosis of Hodgkin's lymphoma can be made by FNA or core needle biopsy, incisional or excisional biopsy is often necessary. Even though RS cells may be found through FNA, they are not pathognomonic for Hodgkin's lymphoma. The presence of RS cells is necessary, but since they are not unique to Hodgkin's lymphoma, RS cells alone are not sufficient for the diagnosis. In addition, FNA is limited in distinguishing subtypes of Hodgkin's lymphoma, especially nodular sclerosing type, because it is important to demonstrate sclerosed bands of tissue around groups of reactive cells interspersed by lacunar-type RS cells.²⁰ Core biopsy may be the first investigation to diagnose Hodgkin's lymphoma; but the sensitivity of CT-guided percutaneous core-needle biopsy from a large series of biopsies of mediastinal Hodgkin's lymphoma was 78%.²¹ However, obtaining an adequate amount of tissue in a core biopsy can be challenging. A CT-guided core needle biopsy in our patient showed “granulomatous inflammation” which led to the differential diagnoses of mediastinal granulomatous inflamation including infections (especially tuberculosis given her origin in Thailand), vasculitis, and immunological aberrations.^22–31 However, granulomatous inflammation is also common in nodular sclerosing Hodgkin's lymphoma (Table 2). Moreover, our patient presented with other characteristics suspicious for Hodgkin's disease including her age, sex, palpable cervical lymphadenopathy, mediastinal mass, and generalized pruritus. As in our patient, adequate tissue via incisional or excisional biopsy should be obtained when there exists a suspicion of Hodgkin's lymphoma but the initial pathologic diagnosis is inconclusive.

Table 2.

Reported causes of graunloma mediastinal mass²²–³¹

	Incidence	Presentations	Complications	Diagnosis / Work-up
Fibrosing granulomatous mediastinitis (as a complication of infectious mediastinal masses)	Rare but incidence is not available Histoplasmosis is the most common cause	2nd – 5th decades with cough, dyspnea, hemoptysis, SVC syndrome, dysphagia, and cor pulmonale	Encasement and obliteration of the tracheobronchial tree, mediastinal vessels and esophagus	Thoracotomy and histopathology are required
Hodgkin's Lymphoma; nodular sclerosing	Nodular sclerosing Hodgkin's has a predilection for the anterior mediastinum A bimodal age distribution More common in middle-aged women	Asymptomatic Cervical or supraclavicular lymphadenopathy, puritus, alcohol intolerance	SVC syndrome and chest wall invasion are uncommon Airway obstruction	Tissue excision Elevated LDH, ESR
Idiopathic (sarcoidosis)	Rare to less than 10%	Hilar adenopathy	Pulmonary fibrosis Increased risk for cancer, in particular lung cancer, malignant lymphomas	Serum ACE elevation in 60%
Infectious causes	The following rare infectious causes: Tuberculosis Syphilis Histoplasmosis Nocardiasis Actinomycosis Blastomycosis Coccidioidomycosis Aspergilliosis	Asymptomatic Cough, dyspnea, pain in the chest, fever, wheezing, dysphagia, and hemoptysis	The most common cause of benign obstruction of the SVC Fibrosing mediastinitis (histoplasmosis is the most common)	Cultures
Wegener's granulomatosis	Middle-aged white 2% among 302 patients in one retrospective study	Upper airway, lungs, and kidney involvement Skin, mucous membranes, eyes, ears, and joints	Sinusitis, tracheal stenosis Relapses Long-term complications (86%): chronic kidney disease, hearing loss and deafness.	Exclude other diagnosis Granulomatous inflammation, geographic necrosis, and vasculitis cANCA, serum creatinine, urine sediment

Conclusion

Our case demonstrates an atypical presentation of nodular sclerosing Hodgkin's lymphoma in an asymptomatic woman whose initial complaint was a breast mass. The extension to the chest wall, compression of the trachea, and lack of respiratory symptoms given the degree of compression are extremely rare in Hodgkin's disease. Moreover the initial biopsy revealed only granulomatous inflammation further confounding the diagnosis. Despite the unusual presentation, Hodgkin's lymphoma, a highly curable malignancy, was in the list of differential diagnoses. Open biopsy was appropriate and the patient responded well to treatment.

Disclosure Statement

The authors have no financial disclosures.

Conflict of Interest

No financial support of any kind was received.