Hodgkin’s disease presenting as discharging neck sinuses and a mediastinal mass

Abstract

A 23-year-old Asian lady presented with a hard indurated midline neck swelling of 2 months duration without any upper aerodigestive tract or systemic symptoms of note. Her inflammatory markers were elevated and she was commenced on antibiotics. Ultrasound scan and fine needle aspiration cytology (FNAC) were inconclusive. A CT scan showed an ill-defined soft tissue mass anterior to and not well demarcated from the thyroid, and contiguous with a superior and anterior mediastinal mass. Incisional biopsy revealed necrosis and pockets of purulent material.

Microbiology suggested a chronic pyogenic abscess negative for acid fast bacilli. She was treated with antituberculous therapy without resolution. She developed a discharging lateral neck mass with progressive increase of the mediastinal mass. She subsequently required a neck exploration and mediastinoscopy. Repeat mediastinal biopsies confirmed the diagnosis of Hodgkin’s disease and no organisms on culture. She was commenced on chemotherapeutic treatment with a satisfactory outcome.

Background

Discharging neck sinuses is an exceptionally rare presentation of Hodgkin’s disease only previously reported once in literature. There are crucial lessons to learn in managing neck abscesses and considering differential diagnoses. It was a challenging case with management dilemmas especially with sterile biopsies in the face of no disease resolution despite treatment.

Case presentation

A 23-year-old Asian lady presented with a neck swelling which she noticed 2 months previously after what she thought was an insect bite. The swelling had persisted despite antihistamines and steroids prescribed by her primary care doctor. She was then referred to an ENT department.

On further questioning, there were no constitutional symptoms and no other symptoms, such as dysphagia or change in voice. Examination revealed a nodular hard indurated mass in the region of the thyroid gland.

She was studying law in university, lived with her mother, a non-smoker who drank little alcohol. No weight loss but had night sweats for a few months. There was a strong family history of thyroid cancer.

Investigations

Blood tests

Initial blood test results showed a white cell count of 16 000, an erythrocyte sedimentation rate of 51 and C reactive protein of 60.

USS and FNAC

Ultrasound scan (USS) and fine needle aspiration cytology (FNAC) were not conclusive.

USS

Thyroid appeared grossly normal. There was a heterogenous abnormal lobulated added tissue surrounding the right lobe of the thyroid possibly arising from the lower pole which appeared irregular and extended anteriorly to the isthmus. The soft tissue was heterogenous, hypoechoic and contained a significant amount of vascularity. Anterior to the isthmus approximately 17 mm and to the right lobe 2.4 cm. Exact nature was unclear.

FNAC 1

Abundant material consisting mainly of a few macrophages and a scattering of cells with enlarged pleomorphic damaged nuclei as in the previous aspirate. Unfortunately, the preservation of the suspicious cells was poor and identification was not possible. Formal biopsy was suggested to exclude a degenerate malignancy.

FNAC 2

The smears showed sheets of neutrophils and neutrophil debris admixed with a few lymphocytes. Granular macrophages were noted. Localised clusters of epitheloid macrophages were not a feature. The appearances were consistent with acute suppurative/purulent inflammation compatible with a pyogenic abscess.

CT neck and thorax

There was a very ill-defined soft tissue mass showing a few cystic areas, anterior to the thyroid and inseparable from the strap and lower sternomastoid muscles on both sides of the midline (figure 1). The mass extended under the right lobe of thyroid, compressed the trachea and displaced it to the left. The mass extended around the inferior pole of the right thyroid lobe where the thyroid looked irregular. Inferiorly, the mass extended behind the manubrium where it was contiguous with a 3.2 cm anterior mediastinal mass showing central necrosis and extending down to the level of the carina (figure 2). There were bilateral level IV/supraclavicular fossa nodes clustered together. There were no obvious bony or pulmonary metastases.

Figure 1.

CT scan showing the anterior neck mass in close relation with the thyroid.

Figure 2.

Mediastinal extension of the midline neck mass on CT scan.

Incisional biopsy

She had an open incision biopsy of her neck mass and this showed very thick indurated tissue in the subcutaneous plane with involvement of the strap muscles. There were the two necrotic areas noted within the swelling, that produced a scanty purulent discharge and swabs were sent for culture and sensitivities. Biopsies were taken of the soft tissue mass and also of the right lower pole of the thyroid gland. The soft tissue mass communicated with the lesion in the anterior mediastinum and this was explored with suction. There was only minimal discharge obtained.

Microbiologic analysis

Microbiological examination revealed no growth on culture and the specimen was negative for acid fast bacilli (AFB).

Histology

Both specimens from the neck and mediastinum consisted of fibrous connective tissue showing large numbers of inflammatory cells including neutrophil and oeosinophil polymorphs and macrophages. There were scattered large atypical cells, both mononuclear and multinucleated. Some of these cells contained large oeosinophilic nucleoli.

Histology of all the specimens showed chronic active suppurative/purulent infection involving striate muscles and fibroconnective tissue – most probably representing a chronic pyogenic abscess (figures 3–5). There was no evidence of neoplasia in any of the sections examined. There was no evidence of a granulomatous inflammation or a primary vasculitis.

Figure 3.

Preliminary histology (chronic pyogenic features).

Figure 5.

Preliminary histology (chronic inflammatory features; magnified).

Figure 4.

Preliminary histology (chronic inflammatory features).

Repeat CT scan

A repeat CT scan showed no further increase in the size of the neck swelling. However, there was further cystic degeneration within the anterior mediastinal mass.

Mediastinoscopy revealed excess granulation tissue with a fistulous tract to the mass in the neck. Pus was evacuated, and multiple biopsies were taken.

Immunologic studies

Immunoglobulin and complement studies were all within normal limits except for a slightly raised antineutrophil cytoplasmic antibodies at a dilution of 1:160.

Immunohistochemistry showed the large cells were leukocyte common antigen negative but positive for CD30 (figure 6 and 7). They were also strongly positive for MUM1 and some were weakly PAX5 positive. They were negative for CD20, CD79a, CD3, CD5. The large cells were also negative for Epstein–Barr virus LMP1 protein. It was difficult to interpret the CD15 stain due to strong staining of the large numbers of background polymorphs, but the large cells appeared to be negative for CD15.

Figure 6.

Immunostain CD30 positive for Hodgkin’s.

Figure 7.

Immunostain CD30 positive for Hodgkin’s (magnified).

Conclusion

The appearances were those of classical Hodgkin’s lymphoma (figure 8).

Figure 8.

Histology showing Hodgkin’s on H&E stain.

Supplementary report and second opinion by the regional centre

Agreed the morphology and immunohistochemical findings were entirely in keeping with classical Hodgkin’s lymphoma.

Immunoglobulins

Immunoglobulin G (IgG) 12.5, IgA 1.81, IgM 1.54 g/l (all normal); Eps – no paraprotein detected. T-spot tuberculosis (TB) was indeterminate and interferon-γ TB test was inconclusive but there was no AFB seen in microbiology.

Thyroid autoantibodies

• ▶Microsomal (TPO) Abs – 99 IU/ml (normal).
• ▶Rheumatoid factor – negative.
• ▶Complement assays – C3 (1.18), C4 (0.26 g/l) normal.

Differential diagnosis

• ▶Malignancy for example, Non-Hodgkin’s lymphoma, metastatic head and neck cancers of larynx, thyroid, nasopharynx etc.
• ▶Infections for example, tuberculous neck abscess or syphilis.
• ▶Granulomatous conditions.

Treatment

She initially had a 10-day course of co-amoxiclav and was reviewed with a CT scan which revealed the neck mass and mediastinal mass. An incisional biopsy was carried out of the neck mass and on advice from microbiologists, the patient was commenced on a 6-week course of clindamycin 450 mg three times a day with no effect. Following the incisional biopsy, she then developed a fistulous tract from the incision site which discharged clear, watery fluid.

Symptoms of a tightness in her chest and dyspnoea on exertion started due to the extrinsic tracheal compression. She was then started on empiric antituberculous treatment with rifampicin, ethambutol and pyridoxine for 11 weeks. Again, there was no improvement in her symptoms.

She was referred to cardiothoracic surgeons as no clinical improvement despite antituberculous therapy. The extrinsic compression of the tracheal was causing shortness of breath but FEV1 was 3.28 (99% predicted) with normal saturations. At that time, examination in the clinic revealed two significant fungating lesions, one in the centre of her neck and in line with a previous scar for biopsies and another laterally placed in the neck which looked like an aggregated mass of lymph glands (figure 9). The masses were extremely tender and discharged pus. White cell count was 26 000 and haemoglobin was 9.6 on this occasion.

Figure 9.

Hodgkin’s disease presenting as discharging neck sinuses.

The patient then underwent exploration of neck wounds with debridement and follow-on mediastinoscopy. Excess granulation tissue was removed from both lesions and pus was evacuated. The edges of the wounds were excised until healthy skin and subcutaneous tissue was identified. It was found that there were underlying sinuses to both wounds. The sinuses were curetted. Multiple biopsies were taken in the mediastinum. Frozen section showed abscess cavity wall with no evidence of malignancy. None of the material extracted from the patient’s neck could grow any organisms. In particular, AFB were not seen. The final report on the formal histology from material removed from the patient’s neck revealed a diagnosis of classical Hodgkin’s lymphoma on immunostain CD30.

Outcome and follow-up

The haematological oncology multidisciplinary team discussion and review of histology showed classical Hodgkin’s disease stage 2E. The letter ‘E’ indicates the malignancy is local but has gone beyond the lymph node into surrounding tissue.

She was subsequently offered treatment on the RATHL TRIAL: a randomised phase III trail to assess response adapted therapy using fludeoxyglucose-positron emission tomography (FDG-PET) imaging in patients with newly diagnosed, Hodgkin’s lymphoma.

She was placed on the ABVD regime (doxorubicin, bleomycin, vinblastine, dacarbazine) and had a PET scan after two cycles of treatment.

NM whole body FDG-PET for staging report

Extensive bilateral supraclavicular and superior mediastinal lymph node involvement (figures 10–13). Soft tissue mass in the right upper lobe measuring up to 5.8 cm with increased metabolic activity. Multiple pulmonary nodules in the right lung with increased metabolic activity. There appeared to be only disease above the diaphragm. Extensive diffuse uptake in the skeleton suggested marrow involvement but was very homogenous and may be physiological. A bone marrow aspirate was suggested and performed.

Figure 10.

Positron emission tomography scan showing intrathoracic disease on the right.

Figure 13.

Positron emission tomography scan showing lateral whole body view with large anterior mediastinal mass and neck disease.

Figure 11.

Positron emission tomography scan showing multiple cervical lymphadenopathy and neck involvement.

Figure 12.

Positron emission tomography scan showing anterior whole body view showing extensive disease in neck and thoracic cavity.

Bone marrow

Consistent with a reactive marrow and no evidence of Hodgkin’s lymphoma.

There were prominent megakaryocytes with mature morphology. Erythropoiesis was relatively reduced but with normal morphology. Macrophages active and lymphocytes normal. No atypical cells present.

She had a protracted course of treatment but has gradually responded with a satisfactory outcome.

Certain issues that made management difficult include the repeated sterile microbiology results obtained that could not help with diagnosis or inform treatment. Antituberculous therapy was commenced empirically with non-resolution after several months of treatment. The motivation of the patient also became a factor due to the protracted course of the disease and treatment requiring several biopsies. Even on commencement of chemotherapy for Hodgkin’s disease following diagnosis, there were side effects which included anaemia, tiredness and constipation.

She is having regular follow-up in weekly out-patient haematology clinics. She has responded well to treatment with a repeat PET scan demonstrating an excellent initial response to treatment with no convincing focus of residual activity. Treatment was, however, interrupted following the fifth cycle of chemotherapy due profound neutropenia and ovarian failure with menopausal symptoms. She was commenced on granulocyte colony-stimulating factor (GCSF). The neck and mediastinal abscesses have now resolved.

Discussion

Hodgkin’s disease was first described by Thomas Hodgkin in 1832. It is a potentially curable malignant lymphoma with distinct histology, biologic behaviour and clinical characteristics.¹ There are five types based on the WHO classification,² four of which are referred to as Hodgkin’s disease nodular sclerosis (60–80% of cases), mixed cellularity (15–30%), lymphocyte depleted (<1%) and lymphocyte rich (5%). The fifth type (nodular predominant Hodgkin’s disease; 5%) is a distinct entity with unique features and treatment.¹

The Reed–Sternberg cells are the classic neoplastic histologic finding in Hodgkin’s disease consisting of about 1–2% of the total tumour mass among a wide variety of inflammatory cells.^{3 4} The age-adjusted incidence of Hodgkin’s disease in the USA in 2008 was 2.8 cases per 100 000 individuals⁵ and a worldwide incidence of 62 000 in 2002. The incidence of mixed cellularity and lymphocyte depleted subtypes is higher in developing countries while the nodular sclerosis subtype is most frequent in developed countries.¹

Overall, Hodgkin’s disease is commoner among males than females with a bimodal age distribution in both sexes peaking in young adults (15–24 years) and older individuals (>55 years).¹

Presenting features of Hodgkin’s disease include asymptomatic lymphadenopathy, intermittent fever, chest pain, cough, shortness of breath (with mediastinal masses); and constitutional symptoms or ‘B symptoms’ for example, unexplained weight loss, night sweats, fever, pruritus.

Unusual presentations of Hodgkin’s disease have been reported in literature including an association with HIV,⁶ a markedly elevated IgE,⁷ with heart failure,⁸ as vertebral osteomyelitis,⁹ a solitary skeletal lesion,¹⁰ primary cardiac lymphoma,¹¹ a febrile cholestatic disease,¹² primary hepatic presentation,¹³ in adrenal gland¹⁴ and with a traumatic thoracic haematoma.¹⁵

Rare sites of presentation of Hodgkin’s disease in the head and neck region have been reported in the literature.¹⁶ The sites include in the cerebellum,¹⁷ nasopharynx,¹⁸ scalp,¹⁹ ear lobe,²⁰ cavernous sinus,²¹ larynx,²² central nervous system,²³ intracerebral.²⁴ Unusual presentations in the head and neck also include as limbic encephalitis.²⁵

There have been previous reports of abscess presentations for Hodgkin’s disease and include in the liver,²⁶ lung,²⁷ brain²⁸ and chest wall.²⁹ We found only one report in the literature for suppurative lymphadenitis as the primary presenting feature for Hodgkin’s disease.³⁰

There are a number of treatment approaches for Hodgkin’s disease with treatment individualised for each patient. Treatment choices are based on patient factors, stage of disease and the risk – benefit balance for each proposed treatment. Disease staging can be clinical or pathological and is indicative of prognosis with stages III or IV regarded as advanced disease. Staging can be further divided into whether certain symptoms are absent (A) or present (B). B symptoms include unexplained weight loss, unexplained fever and drenching night sweats. More aggressive treatment may also be required with bulky tumours, high erythrocyte sedimentation rates, multiple splenic tumours or greater intraabdominal involvement.³¹ Treatment may also be dependent on the cell type involved and risk factors such as male gender, age >45 years, stage IV disease, low albumin, low haemoglobin, high white cell counts or lymphopenia.

Stages I and II disease in adults can be treated with radiation and for selected patients, this can be limited to areas above the diaphragm. In children, however, chemotherapy and low-dose radiation is used. For stage III disease, chemotherapy often with radiotherapy is standard while for stage IV, chemotherapy alone is generally recommended. Relapses can be treated with chemotherapy, radiation and bone marrow or blood stem cell transplantation.

Management lessons specific to this case

This was particularly a difficult case to manage as the diagnosis was not immediate and not clear for several weeks despite investigations and treatment with antibiotics and antituberculous medication. The differential diagnoses of mediastinal masses found in the neck included TB, thyroid cancer (given the relationship of the mass to the thyroid on imaging and her strong family history of thyroid cancer) and metastasis from other head and neck sites. Lymphomas must be borne in mind and as this case demonstrates, Hodgkin’s lymphoma is a possibility.

The history suggested an insect or tick borne infection as the underlying problem with subsequent infective lymphadenitis and then fungating neck wounds. There were several sterile studies from microbiological investigation and the histologic specimens suggested a likely chronic pyogenic abscess with no evidence of a granulomatous inflammation. The disease in the meantime did not show signs of resolution despite on-going treatment with antibiotics for weeks.

Eventually, empiric antituberculous therapy (rifampicin, ethambutol and pyridoxine) was commenced following multidisciplinary discussions based on the patient’s background (Asian), the unresolving clinical picture and chronicity, and the lack of substantial pointers from investigations. It is conceivable that the time taken on antituberculous therapy may have allowed disease progression but this was a plausible cause of management although it eventually turned out to be lymphoma.

Every investigation in this case was discussed with multidisciplinary teams as there was a suspected head and neck malignancy. The initial FNAC was an inconclusive test which required repeating. It is well recognised that insufficient samples or inadequately taken samples can cause FNAC results to be inconclusive. Unfortunately, the preservation of the suspicious cells in this case was poor and identification was not possible. It was difficult to proceed to further testing and as such the pathologists requested formal biopsy. More intensive investigations at this point may have yielded a diagnosis much earlier in this patient’s management although there were subsequent extensive tests carried out later. This is one of the learning points for all physicians involved.

At the multidisciplinary team discussions, the anterior mediastinal mass was noted and in retrospect, a cardiothoracic review could have been requested earlier. The Cardiothoracic surgeons subsequently reviewed at a later stage after she had been on antituberculous therapy without any relief. At this stage, she had two significant fungating neck lesions, one in the centre of her neck in line with a previous scar for biopsies and another laterally placed in the neck discharging pus. The lesion just above the suprasternal notch meant that mediastinoscopy was not feasible. Management therefore proceeded with a re-exploration of her neck both for tissue diagnosis and clearance of the mediastinal abscess. The cardiothoracic surgeons confirm that indeed macroscopically sufficient tissue was eventually obtained intraoperatively in this case (especially since diagnosis was uncertain), however, the insufficient yield initially at neck exploration by the ENT surgeons could have been as a result of aspiration using a sucker.

Stage 2 disease can be treated with radiotherapy, however, this patient was enlisted on the RATHL³² trial and has had chemotherapy with ABVD with sustained clinical improvement and resolution of pathology. This is currently a phase III trial in the UK recruiting patients with Hodgkin’s lymphoma stage 2B, 3 or 4 and aims to find out if PET scanning after two cycles of ABVD can inform treatment decisions. It aims to ascertain if people with negative scans can discontinue bleomycin on their treatment regime and if those with positive scans will require more intensive chemotherapy with BEACOPP (doxorubicin, cyclophosphamide, etoposide, procarbazine, bleomycin, vincristine and prednisolone). This patient’s treatment was successful with a negative PET scan and was subsequently assigned to four more cycles which was unfortunately interrupted after the fifth cycle by profound neutropenia and ovarian failure with menopausal symptoms treated with GCSF. The fungating neck and mediastinal masses have resolved completely.

A multidisciplinary approach to management is essential as demonstrated by this case. Professionals from several specialties were involved including otolaryngologists, pathologists, clinical immunologist, radiologists, cardiothoracic surgeons and haematologists. There were several discussions in multidisciplinary team meetings on the best management options at every stage until a firm diagnosis was made.

Learning points.

• ▶This presentation of Hodgkin’s lymphoma with discharging neck sinuses is unusual.
• ▶Hodgkin’s lymphoma needs to be borne in mind as a possible differential by clinicians in managing similar cases.
• ▶Clinicians should aim to provide adequate tissue samples to cytopathologists with differential diagnoses in mind that can be tested for specifically, especially when the diagnosis is uncertain. Hodgkin’s disease should be borne in mind as a potentially rare possibility in similar cases.
• ▶A multidisciplinary approach to the management of Hodgkin’s lymphoma is advocated as demonstrated in this case involving ENT surgeons, respiratory physicians, cardiothoracic surgeons, pathologists, radiologists and haematologists.