Both patterns are characterized by a spectrum of differentiation of the lymphoid cells with numerous small mature lymphocytes in the background resulting in a polymorphic impression at low power assessment Figure 3 a. In follicular hyperplasia, LHAs of variable size with conspicuous TBMs are often evident at low power, and a mixture of centrocytes, centroblasts, and plasma cells is prominent Figure 4 a. Immunoblasts are dominant in paracortical hyperplasia, particularly viral lymphadenopathy. It is important to note, however, that the two reaction patterns, follicular and paracortical hyperplasia, often present together.
Also, temporal changes in the cell composition occur until the RLH resolves and are associated with concomitant cytologic variations. In most cases the etiology of the RLH remains unknown. RLH most frequently affects children and young adults.
Diagnosis of B-Cell Non-Hodgkin Lymphomas with Small-/Intermediate-Sized Cells in Cytopathology
Bacteria, viruses, chemicals, and drugs are the most common inciting agents [ 12 ]. Considering patient age and cytomorphology, the differential diagnosis in most cases will include Hodgkin lymphoma, T-cell lymphoma, and FL. Depending on the degree of cytomorphologic change, ancillary testing may need to be employed to exclude those mimics. After cytologic diagnosis of RLH an attempt should be made to establish the cause by appropriate history, serology, or other investigations, but as mentioned above the etiology may remain undetermined.
If resolution of the lymphadenopathy does not occur, excisional biopsy is warranted. Nodal MZL is a rare neoplasm 1. By definition, nodal MZL presents without evidence of extranodal or splenic disease. LHAs may be present, and only careful examination at higher power may suggest the presence of monotonous neoplastic cells within a background resembling nonspecific RLH. This may be particularly problematic in partially involved nodes. In contrast, in cases with follicular colonization, the smear may contain numerous FCFs.
Rare cases show a monotonous intermediate-size cell pattern at low power assessment. The neoplastic cells may be exclusively monocytoid, but more typically are cytologically polymorphic with monocytoid cells occurring alongside small lymphocyte- and centrocyte-like cells [ 12 ] as well as with elements showing plasma cell differentiation [ 20 ] Figures 3 b and 4 b.
The cytomorphology of such samples, therefore, leads frequently to a broad differential diagnosis including RLH as well as the spectrum of lymphomas with small and intermediate-sized cells [ 23 ]. Finally, an important potential pitfall is peripheral T-cell lymphoma which can mimic MZL morphologically [ 24 ]. MZL usually affects the middle-aged and elderly, although it may occur in children. Clinical history is important with regard to multiple sites of involvement including intraabdominal lymphadenopathy and presence of constitutional symptoms.
Consideration should be given to the possibility of nodal dissemination of extranodal MZL which occurs in approximately one third of the cases [ 20 ]. The clinical course is indolent, but transformation to a large B-cell lymphoma may occur. Ancillary studies are particularly important in making the diagnosis of MZL, but cases in which the reactive cells obscure the neoplastic B-cell population even by immunophenotyping may occur [ 25 ].
FL grade is characterized by a monotonous to somewhat dimorphic pattern, respectively. FL grade 3A or 3B is characterized by a dominant population of large cells resembling centroblasts and is, therefore, not discussed here. The dimorphic pattern may initially cause the false impression of a polymorphic cell composition at low power. Regardless of grade, smears often give the low-power impression of a nodular pattern which can be an important clue to the diagnosis Figure 3 c.
At higher power, the nodules correspond to numerous FCFs populated by small to intermediate-sized centrocytic cells with cleaved nuclei and clumped chromatin Figure 4 c. Cells with deeply cleaved, apparently bilobed nuclei can be conspicuous [ 26 ]. Larger centroblasts characterized by noncleaved nuclei, less dense chromatin, and a narrow rim of dense cytoplasm are rare in grade 1 FL, but occur with increasing frequency in grade 2 where both cell populations may be present in equal numbers.
LHAs and mitotic activity are both uncommon, and the presence of either should raise suspicion for a reactive process which then needs to be distinguished from partial lymph node involvement by lymphoma. Of note, a rare signet-ring variant of FL exists and is due to immunoglobulin stored within the cytoplasm of the neoplastic cells. A diagnostic challenge can be posed by diffuse FL which is rare and characterized by a lack of follicular architecture in which case FCFs would be absent.
The differential diagnosis in this situation would include insufficient sampling of a FL displaying a focal diffuse component. FL occurring before the age of 20 years is rare. Characteristically there is often widespread nodal involvement at diagnosis. Similar grading can be performed on cytological preparations but is not universally accepted [ 27 , 28 ]. The vast majority of FLs are grade 1 or 2. Fine-needle sampling plays an important role in the initial assessment of FL since it allows sampling of multiple sites of involvement so that the optimal site for excisional biopsy if required can be determined.
Similarly, in a case of suspected transformation multiple fine-needle samples improve the chances of finding and documenting progression. MCL is characterized, in contrast to the lymphomas considered previously, by a distinctly monomorphic cell composition [ 29 , 30 ]. Histologically three patterns of MCL occur: The mantle zone pattern, however, is rarely seen in cytologic material.
Most commonly, smears consist of a highly monotonous population of lymphoid cells interrupted only by small round lymphocytes and occasional histiocytes [ 12 ] Figure 3 d. At higher magnification, the cells have subtly irregular nuclear contours reminiscent of centrocytes, dispersed to clumped chromatin, mostly inconspicuous nucleoli, and moderate amounts of cytoplasm. Mitotic figures may be observed, and this feature can be used together with monomorphism and nuclear contour irregularities in differentiating MCL from other lymphomas [ 31 ] Figure 4 d.
Diagnostic challenges may be posed by any of the variants of MCL. The blastoid and pleomorphic variant both display a more aggressive clinical behavior and may enter the differential diagnosis in cases sampled at relapse which can show increased nuclear size, pleomorphism and mitotic activity [ 20 ]. Lymphadenopathy, hepatosplenomegaly, bone marrow, and peripheral blood involvement are frequent. The median survival is 3—5 years and the majority of patients cannot be cured [ 20 ].
Grading of MCL is not performed. However, the estimation of the proliferative fraction either by counting mitotic figures or Ki67 staining has shown prognostic impact [ 32 ]. Given the different prognosis of MCL, ancillary testing to discriminate the above-mentioned variants of MCL from their less aggressive counterparts is crucial. Proliferation centers differ from FCFs in that they do not contain follicular dendritic cells.
Image Gallery: Lymph Node Cytology
At higher magnification, small lymphoid cells with smooth-contoured nuclei and minimal cytoplasm predominate Figure 4 e. Most cases have interspersed intermediate-sized prolymphocytes with dispersed chromatin and obvious nucleolus as well as paraimmunoblasts with broader, pale cytoplasm, vesicular chromatin, and large central nucleolus Figures 4 e and 5 b. Both cell types are most often seen in those ill-defined aggregates corresponding to the proliferation centers, and their presence provides a clue towards the diagnosis. It is the most common lymphoproliferative disorder of adults in Western countries and shows a slight male preponderance.
The disease is rarely seen in individuals of Asian descent. Immunoglobulin gene mutation status and specific cytogenetic abnormalities correlate with disease prognosis [ 20 ], and can be examined using cytologic material. Fine-needle specimens from patients with LPL show a monomorphic, rarely more polymorphic cell composition without a significant number of cell aggregates.
- .
- Il sole ben pagato - Score!
- Through The Eyes Of The Heart: A journey to feel what we can not always see!
- Meine Weltsicht (German Edition).
- In Extremis: Two Novels by W.H. Collier.
The hint to the diagnosis is an admixture of small lymphocytes and plasmacytoid cells Figures 3 f and 4 f. Mature plasma cells may be present, but if dominant, plasmacytoma should be considered in the differential diagnosis. Intranuclear Dutcher bodies and intracytoplasmic Russell bodies may be seen in the neoplastic cells, and occasional multinucleated cells can be present. Importantly, LPL may be indistinguishable from MZL both histologically or cytologically in which case ancillary testing and correlation with clinical presentation are indispensable. LPL is a rare lymphoma and most frequently occurs in elderly patients with slight male predominance.
The disease is often associated with a paraprotein of IgM type, but this is not required for diagnosis. The lymphoma is typically indolent, but transformation to DLBCL and, rarely, Hodgkin lymphoma occurs in a small number of cases [ 20 ].
This is true regardless of the method with which the specimen was obtained: Although smears can be used for immunocytochemistry, it is much more practical to use cell suspensions which can be submitted directly for flow- or slide-based cytometry, or for further processing as cytospins or cell blocks [ 37 ]. Each of these methods has advantages and disadvantages, and their use is guided by the particular clinical circumstance and, importantly, by the cytomorphology of the sample which is the basis for a tentative diagnosis. Because material for ancillary testing may be limited, the initial morphological assessment becomes a crucial step and determines if a particular investigative pathway will ultimately lead to the correct diagnosis.
Some institutions have developed expertise in slide-based cytometry which can be used with specimens of very low cellularity and yields immunophenotyping results similar to flow cytometry [ 14 , 40 , 41 ]. However, flow cytometry protocols using ten or more colors can be similarly informative with extremely paucicellular specimens. PE Prince Edward Island. What best describes your position? Already have an account? Acceptance to the GDPR regulations is required. If slides are being sent to a reference laboratory for interpretation, patient signalment, relevant clinical and laboratory findings, and the degree and extent of lymph node enlargement should be described in detail.
Occasional intermediate lymphocytes red arrow , which are similar in size to neutrophils, have less condensed chromatin and slightly more cytoplasm. Occasional large lymphocytes, sometimes called lymphoblasts black arrow , are larger than neutrophils, and have finely stippled chromatin and nucleoli, along with moderate amounts of basophilic cytoplasm. Numerous RBCs are consistent with blood contamination. Simultaneous aspiration of fat can result in rupture of lymphocytes and a nondiagnostic preparation as shown.
Adipocytes are large cells with a small oval nucleus black arrow , condensed chromatin, and abundant clear cytoplasm. Ruptured lymphocytes appear as smudged pink-to-purple chromatin or as bare nuclei red arrows. Evaluation of the lymphocytes is not possible without intact cytoplasmic and nuclear membranes. Obtaining aspirates of other enlarged nodes or a different area of the affected node is recommended when the slide contains primarily adipose tissue. Due to close proximity, the mandibular salivary gland can be mistakenly aspirated when attempting to collect a sample from the mandibular lymph node.
In this sample, note how the RBCs are arranged in a linear array windrowing from the viscosity of the mucus. The salivary gland epithelial cells black arrows occur individually or in small clusters and are characterized by abundant, vacuolated basophilic cytoplasm and round nuclei with condensed chromatin. Notice how these epithelial cells are much larger than the neutrophil in the lower right corner red arrow. Three macrophages black arrows are characterized by abundant, vacuolated cytoplasm and irregularly shaped nuclei, with moderately condensed chromatin. Four plasma cells red arrows , similar in size to the neutrophil blue arrow , have eccentric nuclei, condensed chromatin, and abundant deeply basophilic cytoplasm that often contains a perinuclear clear area Golgi region.
In addition, numerous small lymphocytes, an intermediate lymphocyte yellow arrow , and several RBCs are present. Plasma cell hyperplasia can develop with antigenic stimulation. Macrophagic inflammation can be attributed to infectious agents e. Note the size of 2 large lymphocytes black arrows , as compared with the neutrophils gray arrow. Note that the neutrophil granules stain more eosinophilic in this preparation, but are not as prominent as eosinophil granules see Figures 7 and Two of the several plasma cells contain numerous distinct clear inclusions red arrows ; these plasma cells are referred to as Mott cells , which have inclusions ie, Russell bodies packed in the cytoplasm.
Russell bodies are typically round but can vary in size, shape, and color and can result from dilation of the rough endoplasmic reticulum during antibody production. Also present are numerous broken lymphocytes and RBCs.
The sharply demarcated refractile areas in the RBCs are a common artifact. Most of the cells are neutrophils red arrows , which are difficult to identify because they are degenerate and slightly out of focus to more clearly show the yeast form of Blastomyces dermatitidis gray arrows.
These large fungal organisms have characteristic features on routine staining: Several macrophages black arrows are also present. Mixed inflammation characterized by neutrophils and macrophages is typical of blastomycosis. Increased numbers of neutrophils and eosinophils can indicate inflammation. Presence of a high proportion of eosinophils can be associated with hypersensitivity reactions, parasitic infection, neoplasia e.
Inflammation can be accompanied by lymphoid and plasma cell hyperplasia, as shown here, depending on the type of antigenic stimulation. Numerous small lymphocytes, several intermediate lymphocytes red arrows , and a macrophage black arrow also are present. Several plasma cells white arrows and eosinophils yellow arrows are seen in the field. Diffuse large cell lymphoma, the most common form of lymphoma in dogs, is characterized by lymphocytes larger in diameter than a neutrophil yellow arrow. The chromatin pattern is fine, and one to multiple prominent nucleoli are evident. A mitotic figure is found in the upper right corner black arrow.
These large cells are often fragile, and cytoplasmic fragments sometimes referred to as lymphoglandular bodies may be present in the background red arrows. Diagnosis of lymphoma may be confounded by superimposition of the hyperplastic response.
Pathology Outlines - Dermatopathic lymphadenitis
The cytologic diagnosis of lymphoma involving small or intermediate lymphocytes can be more challenging and often necessitates biopsy, immunophenotyping by flow cytometry, or DNA based testing for confirmation. Aspiration of regional lymph nodes may be helpful in determining whether a neoplasm has metastasized, as seen with this carcinoma. The neoplastic cells red arrows form cohesive clusters typical of cells of epithelial origin and exhibit many characteristics of malignancy: These cells have a moderate amount of gray-blue cytoplasm with clear, punctate vacuoles.
A population of primarily small lymphocytes and occasional intermediate and large lymphocytes confirms that this aspirate was obtained from a lymph node. When a node is effaced by neoplastic cells, lymphocytes may not be present. Modified Wright-Giemsa stain, original magnification x. Sign In or Create an Account. Close mobile search navigation Article navigation. Address reprint requests to Dr. Department of Pathology, Box 85, U. You do not currently have access to this article.
You could not be signed in. Sign In Forgot password? Don't have an account? American Society for Clinical Pathology members Sign in via society site.
- .
- XXX: Erotic Short Stories 2?
- Fine needle aspiration cytology for lymph nodes: a three-year study..
- Radiology - A High Yield Review For Nursing Students (1).
- Learn Italian Vocabulary - English/Italian Flashcards - Clothing (Flashcard eBooks)!
- .
- Mountain Drifter [Coastal Del Rey].
Sign in via your Institution Sign in. Purchase Subscription prices and ordering Short-term Access To purchase short term access, please sign in to your Oxford Academic account above. This article is also available for rental through DeepDyve.