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CASE REPORT
Year : 2022 | Volume
: 26
| Issue : 3 | Page : 23-25
A rare case of lethal midline granuloma posing a diagnostic challenge in COVID times and the response to chemotherapy
Ajeet Singh1, Ripudaman Arora2, Satyaki Ganguly1, Rahul Satarkar3
1 Department of Dermatology, Venereology and Leprosy, All India Institute of Medical Sciences, Raipur, Chhattisgarh, India
2 Department of ENT and Head and Neck Surgery, All India Institute of Medical Sciences, Raipur, Chhattisgarh, India
3 Department of Pathology, All India Institute of Medical Sciences, Raipur, Chhattisgarh, India
Correspondence Address:
Dr. Ajeet Singh
Department of Dermatology Venereology and Leprosy, All India Institute of Medical Sciences, Raipur - 492 099, Chhattisgarh
India
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/jdds.jdds_56_21
Lethal midline granuloma is a rare aggressive, mutilating disorder of the upper airways. It is most likely secondary to natural killer/T-cell lymphoma and is difficult to diagnose owing to the varied and nonspecific symptoms. It is usually prevalent in the fourth decade of life and carries a poor prognosis. Our patient was a 19-year-old male with disease duration of 3 months, was diagnosed with lethal midline granuloma based on clinical examination, histopathology, and immunohistochemistry. The patient responded well to the first cycle of chemotherapy.
Keywords: Immunohistochemistry, midline lethal granuloma, T-cell lymphoma
Lethal midline granuloma also known as Stewart syndrome is a rare aggressive, mutilating disorder involving the nose, midline facial tissues, and upper airways. The disease has heterogeneous pathogenesis mostly secondary to underlying natural killer (NK)/T-cell lymphoma and Wegener granulomatosis. It often present with nonspecific symptoms such as rhinorrhea, nasal stuffiness, epistaxis, and pain. This nonspecificity of symptoms makes it difficult to diagnose in the early stage which could be detrimental for the overall prognosis.[1] Here, we report the case of a young boy with lethal midline granuloma and its response to treatment.
Case ReportA 19-year-old male, referred from the otorhinolaryngology department, presented with swelling over the left lower face and ulceration over the left side of the nose involving alae nasi and corresponding nasal mucosa as well as left cheek for 3 months. There was also accompanying history of nasal stuffiness and nasal obstruction for the past 1 month. There was no history of cough or hemoptysis and any other systemic disease.
Cutaneous examination revealed the presence of an ulcer of size 5 cm × 2 cm present over the left side of the dorsum of the nose extending from alae nasi to the left cheek and also involving nasolabial folds and nasal mucosa on the corresponding side. Floor of the ulcer was covered with crust and slough and the base was indurated and the ulcer was tender on palpation. Nasal cavity was filled with crust-like mass also visible on the right side indicating a septal perforation. There was diffuse swelling on the left side of the face also involving the left eyelids and mandibular region. There was deviation of the nose to the right side [Figure 1]. On palpation, the swelling over the mandibular area was firm to hard and nontender. There was cervical lymphadenopathy on the left side of the neck which was stony hard and nontender on palpation. His routine investigations were within the normal limits. Head-and-neck computed tomography showed soft-tissue thickening in the left nasal cavity and maxillary sinus causing deviation of the nasal septum to the right side. There was also soft-tissue mass adjoining to the left mandible.
Figure 1: (a) Well-defined ulcer covered with crust and slough present over the left side of the face involving left nose and swelling of the left half of the face and eyelids; (b) Ulcer extending into the left nasal cavity. Crust-like mass present in nasal cavity along with the deviation of nasal septum to right sideLymph node biopsy from the left cervical lymph node showed completely effaced architecture of lymph node with the formation of nodules and extensive areas of necrosis. Diffuse proliferation of small to medium to large cells and angiodestruction was also present. Histopathological examination from the edge of the ulcer showed nodular infiltrates of small and large lymphocytes involving the whole dermis. The infiltrate was arranged in poorly defined nodules and within the granuloma, large lymphocytes with irregular nuclei, and occasional eosinophils were present. Periodic Acid-Schiff (PAS) stain and Giemsa stain were negative for any fungal elements. Immunohistochemistry (IHC) on tissues from both lymph node and lesion showed positivity for CD3, CD5, CD45, CD56, granzyme, and was negative for CD19 and CD20 [Figure 2].
Figure 2: (a) Poorly defined nodular infiltrates of small and large lymphocytes with irregular nuclei and occasional eosinophils involving whole of dermis; (b) Immunohistochemistry on tissues showing positivity for CD3+ve; (c) CD56 positivity on immunohistochemistry; (d) Granzyme positivity on immunohistochemistryHence, a diagnosis of extranodal NK/T-cell lymphoma, nasal type was made, and the patient was referred to the medical oncology department where he was administered cisplatin 28 mg intravenous (IV) (days 1–4), dexamethasone 21 mg IV (days 1–5), gemcitabine 1120 mg IV (days 1 and 8), and L-asparaginase 3500 IU intramuscular on day 1 (DDGP protocol) to be repeated every 3 weeks. The patient showed remarkable improvement on follow-up after the first cycle of treatment [Figure 3].
Figure 3: Follow-up after 2 months with ulcer in the healing phase and visible improvement in the facial swelling on left side Discussion Lethal midline granuloma is a rare disease which was first described by McBride in 1897.[2] They are mainly nonHodgkin lymphomas (NHLs) and can be either extranodal NK/T-cell lymphoma or B-cell lymphoma. Extranodal NK/T-cell lymphomas account for 7%–10% of the NHLs; however in India, they constitute around 0.5%–1% of NHLs and 5% of peripheral T-cell lymphomas.[3],[4] They are currently classified as extranodal NK/T-cell lymphoma by the World Health Organization–European Organization for Research and Treatment of Cancer classification 2018.[5]
The disease has a male preponderance (male: Female 8:1) and usually occurs in the fourth decade of life and is seen mostly in the Asian and Mexican region.[3] Clinically, the lesions are characterized by ulceration and destruction of the nose and the paranasal sinuses along with the erosion of soft tissues, bone, and cartilage of the region. The disease has an aggressive and lethal course with perforation of the nasal septum and mutilation of the surrounding tissues (midline). The major symptoms are nasal stuffiness, epistaxis, and pain with or without nasal discharge.[1] There can be the presence of oral or nasal ulcer along with conjunctivitis.[6] Microscopically, it is characterized by diffuse lymphomatous infiltrate and angiocentric and angiodestructive growth by the tumor cells that vary in size.[1] These tumor cells are characteristically NK cells, may harbor Epstein-Barr virus in a clonal episomal form and express T cell markers on their surface. NK cells develop from precursor cells which can differentiate into NK/T cells and that could be the reason of some NK cells expressing T-cell markers. The most common immunophenotype is CD3+, CD56+, CD2+, and surface CD20−.[4],[7]
The patient in the present case presented with an acute history of 3 months and a fulminant course. His lesional biopsy showed angiodestructive pattern with atypical lymphoid cells showing CD56 positivity on IHC. Differentials include trauma, trigeminal trophic syndrome, infections (fungal: Aspergillosis, mucormycosis; bacterial: Tuberculosis, syphilis, leprosy, rhinoscleroma, and actinomycosis), cocaine abuse, inflammatory (sarcoidosis, Wegener's granulomatosis, and systemic lupus erythematosus), and neoplasms (basal cell carcinoma, esthesioneuroblastoma, rhabdomyosarcoma, and lymphoma). As there is increased incidence of mucormycosis in India in the COVID pandemic, so PAS staining was also performed on histopathology in our patient, which turned out to be negative.
Nasal NK/T-cell lymphoma is an aggressive tumor and mortality is approximately 100% in untreated cases secondary to sepsis, perforation into blood vessels, and brain abscess.[4],[8] The recent advent of the DDGP protocol of chemotherapy has led to better efficacy (complete response rate 60%) and increased overall survival rates.[9]
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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