|Year : 2021 | Volume
| Issue : 2 | Page : 65-69
An unusual cause of cavitating nodules in the lung: A case review
Ravindran Chetambath1, K Pavithran2
1 Department of Pulmonary Medicine, DM Wayanad Institute of Medical Sciences, Wayanad, Kerala, India
2 Department of Medical Oncolology, Amrita Institute of Medical Sciences, Kochi, Kerala, India
|Date of Submission||16-May-2021|
|Date of Decision||26-May-2021|
|Date of Acceptance||27-May-2021|
|Date of Web Publication||21-Jun-2021|
Dr. Ravindran Chetambath
Navaneeth, Sarovaram Biopark Road, Eranhipalam, Calicut - 673 020, Kerala
Source of Support: None, Conflict of Interest: None
A case of fever, cough, and hemoptysis in a young female which could not be diagnosed by routine investigations is presented here. Confirmatory diagnosis was established after a long period of 2 years. Difficulty in diagnosis itself points to a rare cause for this presentation. The case is presented here with expert comments from specialists working in related specialties.
Keywords: Antineutrophil cytoplasmic antibodies, cavitating nodules, hemoptysis, lymphocytic infiltrates
|How to cite this article:|
Chetambath R, Pavithran K. An unusual cause of cavitating nodules in the lung: A case review. J Adv Lung Health 2021;1:65-9
|How to cite this URL:|
Chetambath R, Pavithran K. An unusual cause of cavitating nodules in the lung: A case review. J Adv Lung Health [serial online] 2021 [cited 2021 Jul 28];1:65-9. Available from: http://www.jalh.com/text.asp?2021/1/2/65/318906
| Introduction|| |
Clinician tends to think of common causes for a constellation of symptoms and signs. Most of the time it works but once in a while a very rare case reports with such a presentation and it eludes the diagnosis even after a battery of investigations. Here, such a case is being presented to highlight on rare diseases manifesting as cavitating nodules in the lungs.
| Case Report|| |
A 29-year-old female homemaker was referred from district hospital with a history of recurrent fever and hemoptysis for the past 2 years. Fever lasted for 2–5 days and subsides on symptomatic treatment. There was cough with scanty expectoration and recurrent bouts of hemoptysis. She used to cough out 5–10 ml of blood which persisted for 2–3 days. She had 3 similar episodes in the past 1 month alone. There was associated loss of appetite and loss of weight. She lost 4 kg weight during the past 2 years. Mild exertional dyspnea was there, but there were no wheezy episodes. She had no other systemic symptoms. There was no history of asthma or frequent respiratory infections in the childhood. There was no history of known allergy. There was no contact history of tuberculosis (TB). She is married and has no children. She was not exposed to passive smoking. She was put on antituberculous treatment since the last 2 months from local hospital considering the prolonged history of fever, cough, and hemoptysis. She had no demonstrable difference in her symptoms.
On examination, she was found to be of average built with a body weight of 48 kg and a body mass index of 18.11. She was alert and cooperative. There was anemia. There was no clubbing or generalized lymphadenopathy. Respiratory system showed a normal upper respiratory tract and bibasilar crackles on both sides. Cardiovascular and gastrointestinal systems were within normal limits. There was no focal neurological deficit.
Her routine blood and urine examination results are shown in [Table 1].
|Table 1: Results of routine blood and urine examination at the time of admission|
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Dr. Ameer K A. MD, DNB, Senior Consultant Pulmonologist, KIMS Hospital, Trivandrum.
This young female with recurrent symptoms of fever and hemoptysis of 2-year duration with loss of appetite obviously suggests a chronic pathology, and TB is to be considered first in differential diagnosis, especially with bilateral patchy infiltrates with few lesions cavitated.
However, the presence of significant neutrophilic leukocytosis is unlikely in TB. Initiation of anti-TB treatment without confirmation was not justifiable. A malignant process of this duration is also unlikely. A vasculitis disorder of limited granulomatosis with polyangitis (GPA) is one closest differential diagnosis. Leukocytosis can be part of GPA. Antineutrophil cytoplasmic antibodies (ANCA)-negative vasculitis was considered here. ANCA evaluation is usually done by immunofluorescence. It can be less sensitive than PR3 and myeloperoxidase (MPO) assay which are by enzyme-linked immunosorbent assay method. Ten percent of GPA can be ANCA negative. A PR3 and MPO assay if done may be more useful.
The next possibility with this clinical scenario to be considered is IgG4-related lung disease (IgG4 RLD). The total IgG4 subclass estimation in serum also can be suggestive. However, this type of leukocytosis is not reported with IgG4 RLD.
The condition is very responsive to steroid. In this case, the initial response was due to steroid. But when steroid was stopped and treatment continued with cyclophosphamide alone, relapse occurred. After confirmation of IgG4 RLD with immunohistochemistry (IHC), continuation of adequate dose of steroid for adequate period can induce remission.
Another possibility with this type of leukocytosis is Sweet's Syndrome (acute febrile neutrophilic dermatosis) with lung involvement. However, there is no skin lesions described in this case.
Any unusual type of lymphoreticular disorder with this type of leukocytosis and thrombocytosis and chronic lung infiltrates requires IHC analysis of biopsy specimen and a multidisciplinary team consensus for accurate diagnosis.
Dr. Bhoomi Angirish – MD, DNB, Consultant Radiologist, Dr. Bhavin Jankharia – MD, DMRD, Chief and Senior consultant, “Picture This,” Mumbai, Maharashtra.
Radiographs are provided from different time intervals. The first radiograph [Figure 1]a shows patchy nodular opacities in left mid and right lower zones which in subsequent radiographs [Figure 1]b, [Figure 2]a, [Figure 2]b appear as progressive confluent nodular opacities in both mid and lower zones along with widened mediastinal shadows and bilateral hilar lymphadenopathy.
|Figure 1: X-ray chest PA views taken at different times during the course of illness. (a) Nonhomogenous infiltrates seen bilaterally in both mid and lower zones. (b) Nodular lesions in both perihilar regions and consolidation in both lower zones|
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|Figure 2: (a and b) X rays taken during chemotherapy showing nodular lesions and diffuse interstitial infiltrates bilaterally|
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The possible differentials based on radiographs would be lymphoma, sarcoidosis, and GPA.
Computed tomography (CT) scan images of the chest-lung window [Figure 3]a and [Figure 3]b and soft tissue window [Figure 4]a and [Figure 4]b show well-defined nodules in peribronchovascular and perifissural distribution. Some of the nodules show cavitation. Unfortunately, we had limited CT scan images and the available cuts do not show presence of lymph nodes in the mediastinum [Figure 5]a and [Figure 5]b. Based on the available CT scan images, possible differentials would be GPA, TB, sarcoidosis, and lymphoma.,
|Figure 3: Multiple nodular opacities distributed randomly (a). Subsegmental consolidations and subpleural nodules are also seen (b). Nodules are distributed along vascular bundles and subpleurally|
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|Figure 4: (a and b) Computed tomography coronal view showing large nodules and masses with cavitation|
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|Figure 5: (a and b) Mediastinal window shows necrotizing masses bilaterally. There are no detectable mediastinal lymph nodes|
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Since branching pattern of nodules was not observed, TB is unlikely. Cavitation is very rarely seen in lymphoma.
Hence, the best possible differentials based on imaging features and considering the clinical data would be GPA more likely over sarcoidosis.
All the investigations were reported negative. C-ANCA and P-ANCA were negative [Table 2].
Features are suggestive of normocytic, normochromic anemia with neutrophilic leukocytosis and mild thrombocytosis. No atypical cells are seen.
Bone marrow biopsy
Mild myeloid and megakaryocytic hyperplasia (leukemoid reaction).
Bronchial mucosa is normal, no active bleeding detected. There was no intraluminal growth or extraluminal compression.
Bronchial washings were negative for acid-fast bacilli smear and CBNAAT for MTB. Bronchoalveolar lavage for KOH smear and fungal culture were negative.
Transbronchial aspiration cytology showed cellular infiltrates consisting of small lymphocytes and few neutrophils. Epitheloid cells and giant cells were conspicuously absent [Figure 6]a, [Figure 6]b and [Figure 7]a, [Figure 7]b.
|Figure 6: (a and b): Shows trans-bronchial aspiration cytology demonstrating polymorphic lymphocytic infiltration. Epitheloid cells and giant cells were conspicuously absent|
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Nasal endoscopy did not show any evidence of granulomatous lesion or foci of bleeding.
Based on the symptoms and radiological presentation of multiple nodules and masses with cavitation, primary pulmonary lymphoma and ANCA-negative GPA were considered as differential diagnosis. She also has hypothyroidism.
The patient was started on antituberculous treatment from another hospital and completed the initial intensive phase. Considering the poor clinical response and radiological worsening, this was stopped. Large nodular and cavitating lesions in the lung, recurrent hemoptysis, and polymorphonuclear leukocytosis tempted to consider ANCA-negative GPA (Wegener's granulomatosis). Absence of involvement of upper respiratory tract and kidneys pointed toward limited Wegener's granulomatosis.
A multidisciplinary discussion between pathologist, radiologist, medical oncologist, and pulmonologist was conducted and decided to start the patient on cyclophosphamide and pulse steroid. The patient responded initially with reduction in symptoms and total leukocyte count. However, this was transient. After the third course of cyclophosphamide symptoms started reappearing.
CT-guided tru-cut biopsy was performed from one of the lung nodules and the histopathology of this specimen led to a confirmatory diagnosis.
CT-guided lung biopsy – sections from lung biopsy show a diffuse infiltrate of atypical lymphoid cells, separated by bands of hyalinizing to sclerosed stroma. The infiltrate is composed of predominantly mature lymphoid cells with few mixed inflammatory cells. They are scattered within large cells with prominent nuclei, forming sheets of cells at places. There are few small caliber vessels with infiltrate of lymphoid cells within wall.
The background cells show predominantly T-cells which are CD3 positive. The large atypical cells show positivity for CD20, CD30, and PAX5, predominant Ki-67 nuclear expressions. Epstein–Barr virus (EBV) is nonspecific showing nuclear positivity.
Lung biopsy features are suggestive of lymphomatoid granulomatosis (LYG) Grade 2.
Note: A Epstein–Barr encoding region in situ hybridization may be done.
Comments by pathologist
Dr. Nithya Ravindran MD, Pathologist.
LYG is a rare EBV-driven lymphoproliferative disorder predominantly involving extranodal sites, which may often present as a diagnostic quandary due to its nonspecific clinical picture. Lung is the most commonly affected site with a vast majority of patients presenting with bilateral pulmonary nodules of varying sizes. Larger nodules frequently exhibit central necrosis. As clinical and radiological picture can resemble an infective process, it is imperative to rule out the possibility of common infections which can resemble this presentation.
The diagnosis requires a tissue biopsy with the typical picture being that of an angiocentric and angiodestructive polymorphous lymphoid infiltrate comprising of EBV-positive B-cells admixed with reactive T-cells. There are usually a small number of EBV-positive B-cells showing some atypia. The inflammatory background also comprises of a mixed population of immunoblasts, plasma cells, and histiocytes although neutrophils and eosinophils are inconspicuous. Lymphocytic vasculitis with infiltration of the vascular wall is a prominent finding in LYG. The loss of vascular integrity due to the inflammatory infiltrates may lead to tissue necrosis. LYG can be histologically graded into three subgroups, the understanding of which is essential in selecting appropriate management strategies. Further studies including IHC and in situ hybridization for EBV help in the accurate diagnosis of LYG.
The histopathological triad for the diagnosis of LYG is polymorphic lymphoid infiltrates, transmural infiltration of arteries and veins by lymphoid cells, and focal areas of necrosis.
Thus, while working up similar cases, viewing these patients with a high index of suspicion and prompt involvement of radiologists and pathologists for specific diagnostic studies helps in timely referral to the oncologist and streamlining the treatment leading to an overall better outcome for the patient.
Comments by medical oncologist
Dr. K Pavithran MD, DM, FRCP, Prof of Medical Oncology, Amrita Institute of Medical Sciences, Kochi.
The histopathology confirmed the diagnosis of LYG. LYG is a rare EBV-associated lymphoproliferative disorder that is characterized by multiple pulmonary nodular lesions. Biopsy will show lymphocytic invasion of vascular wall. LYG can occur at any age, but it is most commonly seen between the ages of 30 and 50. Lung is involved in more than 90% of the cases (pulmonary LYG-PLG) followed by skin (20%–50%) and kidney (15%–30%). Most common symptoms are cough, fever, skin rash/nodules, dyspnea, hemoptysis, and weight loss. The presence of pulmonary symptoms with poorly defined nodular pulmonary opacities on chest imaging should raise the suspicion of PLG.
Usual differential diagnosis is sarcoidosis, fungal infection, IgG4-related disease, lymphoid interstitial pneumonia, GPA, multicentric Castleman disease, and lymphoma.
High-grade disease (that is symptomatic patients with extensive disease) needs treatment with immunochemotherapy. This patient was treated with rituximab, cyclophosphamide, Adriamycin, vincristine, and prednisolone (R-CHOP). Initially, she responded for 6 months. Then, she progressed.
Prognosis of low risk disease is good, whereas high risk disease is associated with worse outcome.
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
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
[Table 1], [Table 2]