PTGC is treated by excisional biopsy and follow-up. It may occasionally recur and in a small proportion of patients has been reported to subsequently develop Hodgkin lymphoma (usually nodular lymphocyte predominant Hodgkin lymphoma).

PTGCs is characterized by:

- follicular hyperplasia (many follicles),

- focally large germinal centres, with poorly demarcated germinal centre (GC)/mantle zone interfaces (as GCs infiltrated by mantle zone lymphocytes), and

- an expanded mantle zone.

The differential diagnosis of Rosai–Dorfman disease includes both malignant and nonmalignant diseases, such as granulomatosis with polyangiitis, Langerhans cell histiocytosis, Langerhans cell sarcoma, lymphoma, sarcoidosis, and tuberculosis. The disease is diagnosed by biopsy of affected tissues. Microscopic examination of stained specimens will show histiocytes with lymphocytes and possibly other types of cells trapped within them, a phenomenon known as emperipolesis. Upon immunohistochemical staining, the histiocytes will be positive for S100, CD68, and CD163 but negative for CD1a.

Dermatopathic lymphadenopathy is diagnosed by a lymph node biopsy. It has a characteristic pattern of histomorphology and immunohistochemical staining:

- Paracortical histiocytosis

- Melanin-laden macrophages

- Eosinophils

- Plasma cells (medulla of lymph node)

lymphadenopathy is a common biopsy finding, and may often be confused with malignant lymphoma. It may be separated into major morphologic patterns, each with its own differential diagnosis with certain types of lymphoma. Most cases of reactive follicular hyperplasia are easy to diagnose, but some cases may be confused with follicular lymphoma. There are seven distinct patterns of benign lymphadenopathy:

- Follicular hyperplasia: This is the most common type of reactive lymphadenopathy.

- Paracortical hyperplasia/Interfollicular hyperplasia: It is seen in viral infections, skin diseases, and nonspecific reactions.

- Sinus histiocytosis: It is seen in lymph nodes draining limbs, inflammatory lesions, and malignancies.

- Nodal extensive necrosis

- Nodal granulomatous inflammation

- Nodal extensive fibrosis (Connective tissue framework)

- Nodal deposition of interstitial substance

These morphological patterns are never pure. Thus, reactive follicular hyperplasia can have a component of paracortical hyperplasia. However, this distinction is important for the differential diagnosis of the cause.

IPMs are diagnosed by examination of the tissue by a pathologist.

They have a rim of peripheral lymphoid tissue (remnant of a lymph node) and consist of spindle cells with nuclear palisading. Red blood cell extravasation is common and blood vessels surrounded by collagen with (fine) peripheral spokes (amianthoid fibers) are usually seen.

Immunostains for smooth muscle actin and cyclin D1 are characteristically positive. The main histologic differential diagnosis is schwannoma.

The typical patient with angioimmunoblastic T-cell lymphoma (AITL) is either middle-aged or elderly, and no gender preference for this disease has been observed. AITL comprises 15–20% of peripheral T-cell lymphomas and 1–2% of all non-Hodgkin lymphomas.

The morphology of cells was observed by means of bone marrow smear; the immunophenotype was detected by flow cytometry and immunohistochemistry assay.

Blasts more than 20%, with more than 50% of megakaryocytic phenotype.

In blood and bone marrow smears megakaryoblasts are usually medium-sized to large cells with a high nuclear-cytoplasmic ratio. Nuclear chromatin is dense and homogeneous. There is scanty, variable basophilic cytoplasm which may be vacuolated. An irregular cytoplasmic border is often noted in some of the megakaryoblasts and occasionally projections resembling budding atypical platelets are present. Megakaryoblasts lack myeloperoxidase (MPO) activity and stain negatively with Sudan black B. They are alpha naphthyl butyrate esterase negative and manifest variable alpha naphthyl acetate esterase activity usually in scattered clumps or granules in the cytoplasm. PAS staining also varies from negative to focal or granular positivity, to strongly positive staining. A marrow aspirate is difficult to obtain in many cases because of variable degree of myelofibrosis. More precise identification is by immunophenotyping or with electron microscopy (EM). Immunophenotyping using MoAb to megakaryocyte restricted antigen (CD41 and CD61) may be diagnostic.

Complete remission and long-term survival are more common in children than adults.

Prognosis depends upon the cause. One third of cases is associated with a t(1;22)(p13;q13) mutation in children. These cases carry a poor prognosis.

Another third of cases is found in Down syndrome. These cases have a reasonably fair prognosis.

The last third of cases may be heterogeneous, and carry a poor prognosis.

Some patients have no symptoms, spontaneous remission, or a relapsing/remitting course, making it difficult to decide whether therapy is needed. In 2002, authors from Sapienza University of Rome stated on the basis of a comprehensive literature review that "clinical observation without treatment is advisable when possible."

Therapeutic options include surgery, radiation therapy, and chemotherapy. Surgery is used to remove single lymph nodes, central nervous system lesions, or localized cutaneous disease. In 2014, Dalia and colleagues wrote that for patients with extensive or systemic Rosai–Dorfman disease, "a standard of care has not been established" concerning radiotherapy and chemotherapy.

Puppies are first presented with what appears to be staphylococcal pyoderma. Definitive diagnosis requires cytologic and histopathologic evaluations. Cytologic examination of papulopustular lesions of juvenile cellulitis reveals pyogranulomatous inflammation with no microorganisms and carefully performed cultures are negative. Biopsies of early lesions reveal multiple discrete or confluent granulomas and pyogranulomas consisting of clusters of large epithelioid macrophages with variably sized cores of neutrophils. Cytological analysis of joint fluid often reveals sterile suppurative arthritis.

The diagnosis relies on the findings outlined above. In addition, other specific markers of macrophage activation (e.g. soluble CD163), and lymphocyte activation (e.g. soluble IL-2 receptor) can be helpful. NK cell function analysis may show depressed NK function, or, flow cytometry may show a depressed NK cell population.

To diagnose this condition, scans or other imaging tests are used. Enlarged nodes in the vicinity of cancer areas could potentially contain cancer.

Probable patients are observed for few weeks until the cause of lymphadenopathy becomes obvious and they are instructed to return to the doctor if there is increase in node size. Biopsy should be performed in case tests suggest malignancy.

Treatment consists mainly of high dose antibiotics for active infections and prophylactic antibiotics for prevention of future infections. GM-CSF therapy or bone marrow transplant might be considered for severe cases. Prognosis is difficult to predict, but patients receiving treatment are generally able to survive to adulthood.

Pralatrexate is one compound currently under investigations for the treatment of PTCL.

Acute mast cell leukemia is extremely aggressive and has a grave prognosis. In most cases, multi-organ failure including bone marrow failure develops over weeks to months. Median survival after diagnosis is only about 6 months.

Investigators at the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health currently have clinical protocols to study new approaches to the diagnosis and treatment of this disorder.

Clonal T-cell receptor gene rearrangements are detected in 75% of cases, and immunoglobin gene rearrangements are seen in 10% of cases, and these cases are believed to be due to expanded EBV-driven B-cell populations. Similarly, EBV-related sequences can be detected in most cases, usually in B-cells but occasionally in T-cells. Trisomy 3, trisomy 5, and +X are the most frequent chromosomal abnormalities found in AITL cases.

The old diagnostic criteria for the illness included: Chronic non-malignant lymphoproliferation, elevated peripheral blood DNTs and defective in vitro Fas mediated apoptosis.

The new criteria require chronic non-malignant lymphoproliferation (over six months lymphadenopathy and/or splenomegaly), elevated peripheral blood DNTs. A primary accessory in diagnosis is defective in vitro Fas mediated apoptosis and somatic or germline mutation in ALPS causative gene (FAS, FASL, CASP10).

The secondary accessory in diagnosis are elevated biomarkers (plasma sFASL over 200 pg/ml, plasma IL-10 >20 pg/ml, plasma or serum vitamin B12 >1500 ng/L, Plasma IL-18 >500pg/ml) and immunohistochemical findings on biopsy consistent with ALPS as determined by an experienced hematopathologist. Another sign is autoimmune cytopenias and polyclonal hypergammaglobulinemia and a family history of ALPS or non-malignant lymphoproliferation.

A definitive diagnosis is chronic non-malignant lymphoproliferation and/or elevated peripheral blood DNTs plus one primary accessory criterion. A probable diagnosis is the same but with one secondary accessory criterion.

Simple surgical excision is considered curative. Rare recurrences have been reported.

Lymph node enlargement is recognized as a common sign of infectious, autoimmune, or malignant disease. Examples may include:

- Reactive: acute infection ("e.g.," bacterial, or viral), or chronic infections (tuberculous lymphadenitis, cat-scratch disease).

- The most distinctive sign of bubonic plague is extreme swelling of one or more lymph nodes that bulge out of the skin as "buboes." The buboes often become necrotic and may even rupture.

- Infectious mononucleosis is an acute viral infection caused by Epstein-Barr virus and may be characterized by a marked enlargement of the cervical lymph nodes.

- It is also a sign of cutaneous anthrax and Human African trypanosomiasis

- Toxoplasmosis, a parasitic disease, gives a generalized lymphadenopathy ("Piringer-Kuchinka lymphadenopathy").

- Plasma cell variant of Castleman's disease - associated with HHV-8 infection and HIV infection

- Mesenteric lymphadenitis after viral systemic infection (particularly in the GALT in the appendix) can commonly present like appendicitis.

Less common infectious causes of lymphadenopathy may include bacterial infections such as cat scratch disease, tularemia, brucellosis, or prevotella.

- Tumoral:

- Primary: Hodgkin lymphoma and non-Hodgkin lymphoma give lymphadenopathy in all or a few lymph nodes.

- Secondary: metastasis, Virchow's Node, neuroblastoma, and chronic lymphocytic leukemia.

- Autoimmune: systemic lupus erythematosus and rheumatoid arthritis may have a generalized lymphadenopathy.

- Immunocompromised: AIDS. Generalized lymphadenopathy is an early sign of infection with human immunodeficiency virus (HIV), the virus that causes acquired immunodeficiency syndrome (AIDS). "Lymphadenopathy syndrome" has been used to describe the first symptomatic stage of HIV progression, preceding a diagnosis of AIDS.

- Bites from certain venomous snakes such as the pit viper

- Unknown: Kikuchi disease, progressive transformation of germinal centers, sarcoidosis, hyaline-vascular variant of Castleman's disease, Rosai-Dorfman disease, Kawasaki disease, Kimura disease

In pathology, dermatopathic lymphadenopathy, also dermatopathic lymphadenitis, is lymph node pathology due to skin disease.

Historically, hematological malignancies have been most commonly divided by whether the malignancy is mainly located in the blood (leukemia) or in lymph nodes (lymphomas).

However, the influential WHO Classification (published in 2001) placed a greater emphasis on cell lineage.

Relative proportions of hematological malignancies in the United States

The most typical symptom at the time of diagnosis is a mass that is rapidly enlarging and located in a part of the body with multiple lymph nodes.

The definitive diagnosis is arrived at from tissue, i.e. a biopsy, by a pathologist.

MRI or contrast enhanced CT classically shows multiple ring-enhancing lesions in the deep white matter. The major differential diagnosis (based on imaging) is cerebral toxoplasmosis, which is also prevalent in AIDS patients and also presents with a ring-enhanced lesion, although toxoplasmosis generally presents with more lesions and the contrast enhancement is typically more pronounced. Imaging techniques cannot distinguish the two conditions with certainty, and cannot exclude other diagnoses. Thus, patients undergo a brain biopsy.