Lymphoreticular Neoplasia and Other Lesions
Although there is abundant lymphoid tissue in the upper aerodigestive tract, the sinonasal area, unlike the nasopharynx, is surprisingly lacking in both mucosa-associated lymphoid deposits and lymph nodes. This in turn is reflected in the relative paucity of regional lymphadenopathy from most malignant sinonasal tumors. However, the sinonasal area can be the site of a range of lymphoid disorders, from site-specific conditions such as NK/T-cell lymphoma to disseminating tumors that can start there, such as B-cell lymphomas, or more generalized neoplasia which may be associated with deposits in the sinuses—for example, chloroma.
Lymphomas account for <5% of all malignant neoplasms of the head and neck and the nose and sinuses account for ~13% of upper aerodigestive tract lymphomas in general. In our series of malignant sinonasal tumors, they accounted for 12% (Table 14.1).
The classification of hematopoietic and lymphoid tumors has also undergone significant changes in the last few decades in response to a better understanding of genetic predisposition and cellular origin. This has been greatly improved by immunohistochemistry, flow cytometry, cytogenetics and molecular studies, the ability to check T-cell receptor rearrangements, and fusion transcripts. A vast array of conditions are covered in the WHO classification1 and it is beyond the scope of this book to cover all of these in any detail. In its simplest form, the classification relates to cell of origin and is divided into three: myeloid, lymphoid, and histiocytic/dendritic.
We have chosen to concentrate on the lesions that we have encountered, albeit including some rarities. However, several key points emerge that are applicable to all these conditions:
Always have a low threshold of suspicion when confronted by a patient with a condition that is not quite right for simple chronic rhinosinusitis even in the absence of an obvious mass or ulceration.
When taking tissue for biopsy, always provide the pathologist with adequate and representative tissue, avoiding areas of necrosis.
If in any doubt, always ask for tissue to be referred to a center with a special interest in lymphoma and/or sinonasal pathology.
Once the diagnosis is made, the management is primarily medical but should be conducted by oncologists with a special interest in these conditions to obtain the best results and minimize morbidity.
Immunodeficiency-Associated Lymphoproliferative Disorders
Lymphoid Hyperplasia in HIV
Infection with the human immunodeficiency virus puts the individual at a significant risk of developing a range of malignancies in the head and neck from squamous cell carcinoma through Kaposi′s sarcoma to lymphomas, including Burkitt′s lymphoma and diffuse large B-cell lymphoma. As a precursor of the latter, marked lymphoid hyperplasia may be encountered in any part of Waldeyer′s ring, including the nasopharynx where adenoidal enlargement may impinge on the posterior choana, causing nasal obstruction, either bilateral or unilateral. These lesions are characterized by a marked follicular hyperplasia with enlarged germinal centers that are irregular in shape or “serpentine.”2 An HIV test should be considered, with appropriate counseling, in cases of unexplained or new-onset adenoidal hyperplasia.
References
1. Swerdlow S, Camp E, Harris N, et al, eds. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon: IARC Press; 2008:10–13 2. Stelow E, Mills P. Biopsy Interpretation of the Upper Aerodigestive Tract and Ear. Philadelphia: Wolters Kluwer, Lippincott, Williams and Wilkins; 2008:258–260Myeloid Malignancies
Myeloid Sarcomas
Definition
(ICD-O code 9930/3)
A myeloid sarcoma is a tumor composed of myeloid blasts with or without maturation at an anatomical site other than in the bone marrow.1
Synonyms
Extramedullary myeloid tumor, granulocytic sarcoma, chloroma.
Site
These malignancies can occur anywhere in the body but are very rare in the nose and sinuses. They are more often part of a systemic disease (acute myeloid leukemia or other myeloproliferative neoplasms)2,3 but can occur as isolated lesions when they may be overlooked by the unwary. Orbital lesions are commoner than the paranasal sinuses.
Diagnostic Features
Clinical Features
In general most of the case reports, when part of a disseminated leukemia, have been in children or young people, whereas isolated deposits can affect an older age group. Although said to be commoner in men, we have seen three patients, all women (38, 52, and 74 years old) who presented with pain and mild swelling that was mistaken as chronic frontal rhinosinusitis (2 cases) and dacrocystitis (1 case) and in two cases had undergone surgery without improvement. In neither of these cases was tissue taken at the initial surgery, although both patients had abnormal material in the frontal sinus and lacrimal sac, respectively. Once diagnosed, full staging did not reveal disease elsewhere and the patients were all treated apparently successfully with radiotherapy (1, 4, and 8 years follow-up, respectively).
Case reports of sinus deposits may describe headache4 or pain as in our two cases.
Imaging
There are no specific features, as the deposit may initially be confined to the sinus cavity (or sac) but with time will expand and erode the adjacent structures. These are among a small number of malignant tumors that will produce an isolated lesion in the frontal or sphenoid.5 Both CT and MRI, as usual, are helpful and the MRI signal is generally isointense to the brain on both T1W and T2W images.
Histological Features and Differential Diagnosis
Immunohistochemistry with or without flow cytometry will generally confirm the diagnosis when one is confronted by a tumor composed of sheets of neoplastic cells of varying differentiation and phenotype. Most will react with myeloperoxidase, and CD68/KP1 is the most commonly expressed marker, although there are a host of others.6 FISH and other cytogenetics investigations can demonstrate chromosomal abnormalities in around 55% of cases; for example, monosomy 7 or trisomy 8.
The tumor must be mainly distinguished from lymphomas such as lymphoblastic, diffuse large B-cell, and Burkitt′s lymphoma as treatment protocols will differ. Few if any prognostic factors have been determined, although those undergoing bone marrow transplantation as part of their treatment have a higher probability of long-term survival.7,8
References
1. Pileri S, Orazi A, Falini B. Myeloid sarcoma. In: Swerdlow S, Camp E, Harris N, et al, eds. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon: IARC Press; 2008:140–141 2. Barker GR, Sloan P. Maxillary chloroma: a myeloid leukaemic deposit. Br J Oral Maxillofac Surg 1988;26(2):124–128 3. Ferri E, Minotto C, Ianniello F, Cavaleri S, Armato E, Capuzzo P. Maxilloethmoidal chloroma in acute myeloid leukaemia: case report. Acta Otorhinolaryngol Ital 2005; 25(3):195–199 4. O′Brien J, Buckley O, Murphy C, Torreggiani WC. An unusual cause of persistent headache: chloroma (2008: 2b). Eur Radiol 2008;18(5):1071–1072 5. Freedy RM, Miller KD Jr. Granulocytic sarcoma (chloroma): sphenoidal sinus and paraspinal involvement as evaluated by CT and MR. AJNR Am J Neuroradiol 1991;12(2):259–262 6. Quintanilla-Martínez L, Zukerberg LR, Ferry JA, Harris NL. Extramedullary tumors of lymphoid or myeloid blasts. The role of immunohistology in diagnosis and classification. Am J Clin Pathol 1995;104(4):431–443 7. Breccia M, Mandelli F, Petti MC, et al. Clinico-pathological characteristics of myeloid sarcoma at diagnosis and during follow-up: report of 12 cases from a single institution. Leuk Res 2004;28(11):1165–1169 8. Pileri SA, Ascani S, Cox MC, et al. Myeloid sarcoma: clinicopathologic, phenotypic and cytogenetic analysis of 92 adult patients. Leukemia 2007;21(2):340–350Lymphoid Malignancies
Non-Hodgkin′s lymphomas
Diffuse Large B-Cell Lymphoma
Definition
(ICD-O code 9680/3)
Diffuse large B-cell lymphoma (DLBCL) is a neoplasm of large B lymphoid cells with nuclear size equal to or exceeding that of normal macrophage nuclei or more than twice the size of a normal lymphocyte that has a diffuse growth pattern.1
Etiology
While the Epstein-Barr virus (EBV) can be found in association with this lymphoma, it is more common in those affecting the immunocompromised.2 Several molecular and cytogenetic abnormalities may be found as well as chromosomal rearrangements of 3q27 in up to 30% of cases.3 Gene-expression profiling has been used to subdivide DLCBL into two subtypes, one with a profile of germinal center B cells (GCB-like in 45 to 50%) and one of activated peripheral B cells (ABC-like).
Synonyms
In the past the terms malignant lymphoma and lymphosarcoma were used.
Incidence
DLBCL is the most common form of non-Hodgkin′s lymphoma encountered in adults in the West.
Site
Extranodal DLBCL can occur anywhere in the upper aerodigestive tract and throughout the nose and sinuses (and nasopharynx). In our own series of 60 cases, the nasal cavity, followed by maxillary and ethmoid areas, were most often affected, although the orbit was also frequently involved either primarily or by secondary extension.
Diagnostic Features
Clinical Features
DLBCL is generally a disease of older adults. In our series of 60 cases, the patients’ ages ranged from 20 to 89 years with a mean of 58 years. The male-to-female ratio was 2:1 in accord with the literature.4 The patients generally present with a rapidly growing mass, which often involves the adjacent soft tissues and may initially be mistaken for cellulitis. As a consequence patients are often given antibiotics on the presumption of an acute bacterial rhinosinusitis or soft tissue infection. They may also present with orbital symptoms due to a mass effect, or due to infiltration of the apex, or due to the neurologic effects of cavernous sinus involvement.
Imaging
The lesion appears as a soft tissue mass associated with bone remodeling, erosion, or infiltration that shows intermediate enhancement on both CT and MRI, increased by contrast administration (Figs. 14.1, 14.2, 14.3).5
Full staging should be undertaken in all patients, including imaging of the thorax and abdomen, FDG-PET if available, a skeletal survey together with bone marrow aspiration, and full hematological work-up.
Histological Features and Differential Diagnosis
The tumor mass is usually isolated and referred to as “primary” or it can evolve from lower-grade lymphoid tumors such as chronic lymphocytic leukemia/small lymphocytic lymphoma, follicular lymphoma, or extranodal marginal zone lymphomas (secondary). It can also occur following treatment of lymphoma elsewhere in the body as it did in two of our patients (from disease in the testes and shoulder). In the orbit—a condition that in the past was called “pseudotumor,” it is now recognized as a precursor of lymphoma and should be treated as such. These may infiltrate the sinuses and infratemporal fossa, thereby coming within the ambit of the ENT surgeon.
Histologically DLCBLs have large neoplastic cells mixed with smaller more normal-looking lymphocytes. Variants are recognized such as T cell rich and plasmablastic.
This latter more aggressive variety is most often seen in association with HIV infection.2 However, on immunohistochemistry the cells are positive for B cell markers such as CD19, CD20, CD22, and CD79a.6 They do not express cyclin D1, which distinguishes them from mantle cell lymphomas.
Diagnosis can be confused by the accompanying inflammatory infiltrate. Other conditions such as Wegener′s granulomatosis must be excluded.
Natural History
Although DLCBL is quite often an isolated lesion, between 11 and 27% are reported to have bone marrow involvement7 and one-third of these show malignant cells in the peripheral blood.8
Treatment and Outcome
Chemotherapy, in particular CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), has been used as the primary treatment, to which radiotherapy may be added. The International Prognostic Index (Table 14.2) proved reliable for aggressive lymphoma4 in the past, before rituximab was available. At that time long-term remission rate was between 50% and 60%. The addition of the anti-CD20 antibody, rituximab to conventional CHOP regimes has improved outcome significantly, particularly in those over 60 years old,9,10 and it is also used as monotherapy for maintenance and relapse.11 Immunoblastic features and a wide range of immunohistochemical markers have been investigated as prognostic markers, although evidence for their significance is conflicting and has been diminished by the use of rituximab.
Sinonasal NK/T-Cell Lymphoma
Definition
(ICD-O code 9719/3)
This is a slowly progressive, unrelenting ulceration and necrosis of the midline facial tissues. It is a rare form of extranodal non-Hodgkin′s lymphoma and has been designated “NK/T” instead of “NK” because, while most cases appear to be genuine natural killer (NK)-cell tumors, some cases show a cytotoxic T cell phenotype.12
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