Epithelioid cells are an essential characteristic of granulomas: that is to say that without them a histological finding is not a granuloma. A granuloma can be defined as "an organized collection of epithelioid macrophages." A non-purist would give a broader definition of the granuloma as "an organized collection of macrophages." The latter definition would include mere collections of giant cells surrounding inert substances like suture material – the so-called "non-immune granulomas."

Granuloma formation is a strategy that has evolved to deal with those pathogens that have learned to evade the host immune system by various means like resisting phagocytosis and killing within the macrophages. Granulomas try to wall off these organisms and prevent their further growth and spread. Many old scourges of mankind like tuberculosis, leprosy and syphilis fall into this category of diseases. Granuloma formation is also the feature of many of our newer problems like fungal infections, sarcoidosis and Crohn's diseases.

Guidelines for management of patients up to 18 years with Langerhans cell histiocytosis has been suggested. Treatment is guided by extent of disease. Solitary bone lesion may be amenable through excision or limited radiation, dosage of 5-10 Gys for children, 24-30 Gys for adults. However systemic diseases often require chemotherapy. Use of systemic steroid is common, singly or adjunct to chemotherapy. Local steroid cream is applied to skin lesions. Endocrine deficiency often require lifelong supplement e.g. desmopressin for diabetes insipidus which can be applied as nasal drop. Chemotherapeutic agents such as alkylating agents, antimetabolites, vinca alkaloids either singly or in combination can lead to complete remission in diffuse disease.

Excellent for single-focus disease. With multi-focal disease 60% have a chronic course, 30% achieve remission and mortality is up to 10%.

Epithelioid histiocytes (Epithelioid cells) are activated macrophages resembling epithelial cells: elongated, with finely granular, pale eosinophilic (pink) cytoplasm and central, ovoid nucleus (oval or elongate), which is less dense than that of a lymphocyte. They have indistinct shape contour, often appear to merge into one another and can form aggregates known as giant cells.

Plasma cell granuloma is a lesional pattern of inflammatory pseudotumour, different from the "inflammatory myofibroblastic tumor" pattern.

It is linked to IgG4-related disease.

The basis of management is to find and correct the underlying cause. Many times cats with EGC will respond to treatment with corticosteroids or to ciclosporin.

Granuloma is an inflammation found in many diseases. It is a collection of immune cells known as histiocytes (macrophages). Granulomas form when the immune system attempts to wall off substances it perceives as foreign but is unable to eliminate. Such substances include infectious organisms including bacteria and fungi, as well as other materials such as keratin and suture fragments.

Clear cell acanthoma (also known as "Acanthome cellules claires of Degos and Civatte," "Degos acanthoma," and "Pale cell acanthoma") is a benign clinical and histological lesion initially described as neoplastic, which some authors now regard as a reactive dermatosis. It usually presents as a moist solitary firm, brown-red, well-circumscribed, 5 mm to 2 cm nodule or plaque on the lower extremities of middle-aged to elderly individuals The lesion has a crusted, scaly peripheral collarette and vascular puncta on the surface. It is characterized by slow growth, and may persist for years. The clinical differential diagnosis includes: dermatofibroma, inflamed seborrheic keratosis, pyogenic granuloma, basal cell carcinoma, squamous cell carcinoma, verruca vulgaris, psoriatic plaque, and melanoma.

The Xanthogranulomatous Process (XP), also known as Xanthogranulomatous Inflammation is a form of acute and chronic inflammation characterized by an exuberant clustering of foamy macrophages among other inflammatory cells. Localization in the kidney and renal pelvis has been the most frequent and better known occurrence followed by that in the gallbladder but many others have been subsequently recorded. The pathological findings of the process and etiopathogenetic and clinical observations have been reviewed by Cozzutto and Carbone.

Plasma cell gingivits is rare, and plasma cell cheilitis is very rare. Most people with plasma cell cheilitis have been elderly.

Preventing exposure to the causative antigen leads to resolution of the condition. Tacrolimus or clobetasol propionate have also been used to treat plasma cell cheilitis.

Treatment is most commonly directed at autoimmune disease and may be needed to treat bulky lymphoproliferation. First line therapies include corticosteroids (very active but toxic with chronic use), and IVIgG, which are not as effective as in other immune cytopenia syndromes.

Second line therapies include: mycophenolate mofetil (cellcept) which inactivates inosine monophosphate, most studied in clinical trials with responses varying (relapse, resolution, partial response). It does not affect lymphoproliferation or reduce DNTs, with no drug-drug interactions. This treatment is commonly used agent in patients who require chronic treatment based on tolerance and efficacy. It may cause hypogammaglobulinemia (transient) requiring IVIgG replacement.

Sirolimus (rapamycin, rapamune) which is a mTOR (mammalian target of rapamycin) inhibitor can be active in most patients and can in some cases lead to complete or near-complete resolution of autoimmune disease (>90%) With this treatment most patients have complete resolution of lymphoproliferation, including lymphadenopathy and splenomegaly (>90%) and have elimination of peripheral blood DNTs. Sirolimus may not be as immune suppressive in normal lymphocytes as other agents. Some patients have had improvement in immune function with transition from cellcept to rapamycin and it has not been reported to cause hypogammaglobulinemia. Hypothetically, Sirolimus may have lower risk of secondary cancers as opposed to other immune suppressants and requires therapeutic drug monitoring. It is the second most commonly used agent in patients that require chronic therapy. It is mostly well tolerated (though side effects include mucositis, diarrhea, hyperlipidemia, delayed wound healing) with drug-drug interactions. It has better activity against autoimmune disease and lymphoproliferation than mycophenolate mofetil and other drugs; however, sirolimus requires therapeutic drug monitoring and can cause mucositis. A risk with any agent in pre-cancerous syndrome as immune suppression can decreased tumor immunosurvellence. Its mTOR inhibitors active against lymphomas, especially EBV+ lymphomas. The Goal serum trough is 5-15 ng/ml and can consider PCP prophylaxis but usually not needed.

Other treatments may include drugs like Fansidar, mercaptopurine: More commonly used in Europe. Another is rituximab but this can cause lifelong hypogammaglobulinemia and a splenectomy but there is a >30% risk of pneumococcal sepsis even with vaccination and antibiotic prophylaxis

In , a granuloma is an organized collection of macrophages.

In medical practice, doctors occasionally use the term "granuloma" loosely to mean "a small nodule". Since a small nodule can represent anything from a harmless nevus to a malignant tumor, this usage of the term is not very specific. Examples of the inaccurate use of the term granuloma are the lesions known as vocal cord granuloma (known as contact granuloma), pyogenic granuloma and intubation granuloma, all of which are examples of granulation tissue, not granulomas. "Pulmonary hyalinizing granuloma" is a lesion characterized by keloid-like fibrosis in the lung, and is not granulomatous. Similarly, radiologists often use the term granuloma when they see a calcified nodule on X-ray or CT scan of the chest. They make this assumption since granulomas usually contain calcium, although the cells that form a granuloma are too tiny to be seen by a radiologist. The most accurate use of the term "granuloma" requires a pathologist to examine surgically removed and specially colored (stained) tissue under a microscope.

Macrophages (specifically histiocytes) are the cells that define a granuloma. They often, but not invariably, fuse to form multinucleated giant cells (Langhans giant cell). The macrophages in granulomas are often referred to as "epithelioid". This term refers to the vague resemblance of these macrophages to epithelial cells. Epithelioid macrophages differ from ordinary macrophages in that they have elongated nuclei that often resemble the sole of a slipper or shoe. They also have larger nuclei than ordinary macrophages and their cytoplasm is typically more pink when stained with eosin. These changes are thought to be a consequence of "activation" of the macrophage by the offending antigen.

The other key term in the above definition is the word "organized" that refers to a tight, ball-like formation. The macrophages in these formations are typically so tightly clustered that the borders of individual cells are difficult to appreciate. Loosely dispersed macrophages are not considered to be granulomas.

All granulomas, regardless of cause, may contain additional cells and matrix. These include lymphocytes, neutrophils, eosinophils, multinucleated giant cells, fibroblasts and collagen (fibrosis). The additional cells are sometimes a clue to the cause of the granuloma. For example, granulomas with numerous eosinophils may be a clue to coccidioidomycosis or allergic bronchopulmonary fungal disease, and granulomas with numerous neutrophils suggest blastomycosis, granulomatosis with polyangiitis, aspiration pneumonia or cat-scratch disease.

In terms of the underlying cause, the difference between granulomas and other types of inflammation is that granulomas form in response to antigens that are resistant to "first-responder" inflammatory cells such as neutrophils and eosinophils. The antigen causing the formation of a granuloma is most often an infectious pathogen or a substance foreign to the body, but sometimes the offending antigen is unknown (as in sarcoidosis).

Granulomas are seen in a wide variety of diseases, both infectious and non-infectious. Infections that are characterized by granulomas include tuberculosis, leprosy, histoplasmosis, cryptococcosis, coccidioidomycosis, blastomycosis and cat scratch disease. Examples of non-infectious granulomatous diseases are sarcoidosis, Crohn's disease, berylliosis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, pulmonary rheumatoid nodules and aspiration of food and other particulate material into the lung.

An important feature of granulomas is whether or not they contain necrosis. Necrosis refers to dead cells that, under the microscope, appear as a mass of formless debris with no nuclei present. A related term, "caseation" (literally: turning to cheese) refers to a form of necrosis that, to the unaided eye (i.e., without a microscope), appears cheese-like ("caseous"), and is typically (but not uniquely) a feature of the granulomas of tuberculosis. The identification of necrosis in granulomas is important because granulomas with necrosis tend to have infectious causes. There are several exceptions to this general rule, but it nevertheless remains useful in day-to-day diagnostic pathology.

Inflammatory myofibroblastic tumour is a lesional pattern of inflammatory pseudotumour, as plasma cell granuloma. It is abbreviated IMT.

Plasma cells, also called plasma B cells, plasmocytes, plasmacytes, or effector B cells, are white blood cells that secrete large volumes of antibodies. They are transported by the blood plasma and the lymphatic system. Plasma cells originate in the bone marrow; B cells differentiate into plasma cells that produce antibody molecules closely modelled after the receptors of the precursor B cell. Once released into the blood and lymph, these antibody molecules bind to the target antigen (foreign substance) and initiate its neutralization or destruction.

Annular elastolytic giant-cell granuloma (also known as "Giant cell elastophagocytosis," "Meischer's granuloma," "Miescher's granuloma of the face") is a cutaneous condition characterized histologically by a dermal infiltrate of macrophages.

Localized granuloma annulare has a tendency towards spontaneous resolution. Localized lesions have been treated with potent topical corticosteroids.

Eosinophilic granuloma is a form of Langerhans cell histiocytosis. It is a condition of both human and veterinary pathology. Colloquially, the reaction pattern is sometimes referred to as a rodent ulcer.

Feline eosinophilic granuloma complex is synonymous with "feline eosinophilic skin diseases". This is considered to be a cutaneous reaction pattern that can be the manifestation of a number of underlying infections, allergies or ectoparasite infestations. It can also be idiopathic, that is have no known underlying trigger. The eosinophilic reaction is common in feline inflammatory disease and the eosinophilic granuloma can be a hereditary reaction pattern in some lines of domestic cats.

Recent case report studies suggest that treatment regimens which include a proteasome inhibitor drug, particularly bortezomib, and/or autologous stem-cell transplantation have improved pPCL survival. For example, 28 patients treated with a bortezomib-based induction regimen followed by autologous stem-cell transplantation and then a maintenance regimen of lenaldomide (an immunosuppressant related to thalidomide), bortezomib, and dexamethasone (a corticosteroid) has a progression free survival rate of 66% at 3 years and an overall survival rate of 73% at 4 years. In one study, patients receiving intensive chemotherapy plus autologous stem-cell transplantation had a median survival of 34 months while those receiving chemotherapy alone had a median survival of 11 months. Two other studies that included bortezomib in their chemotherapy regimens likewise found that the addition of autologous stem-cell transplantation improved results. Current recommendations for treating pPCL often include induction with a three drug regimen such as borezomib-lenalidomide-dexamethasone followed by autologous stem-cell transplantion and consolidation/maintenance with of combination of immunomodulator agents (e.g. thalidomide, lenalidomide, or pomalidomide) plus a proteasome inhibitor (bortezomib, ixazomib, or carfilzomib.

Prior to the use of newly developed drugs and treatment regimens, median survival rates from the time of diagnosis for pPCL and sPCL were 8-11 months and 2-8 months, respectively, even when treated very aggressively with the VAD regimen of vincristine, doxorubicin, and dexamethasone or the VCMP regimen of vincristine, carmustine, melphalan, and prednisone alternating with vincristine, carmustine, doxorubicin, and prednisone. The treatment of PCL patients, particularly pPCL pateints, with newer methods appears to have made modest improvements in survival rates. However, the rarity of these two leukemias has limited individual studies to case reports on a small number of patients or rectrospective analyses of patient records. Randomized controlled trials on these patients have not been reported. One flaw of these methods is patient selection bias, i.e. patients selected for treatment with a new regimen may be less ill than average patients with the disease and therefore have an intrinsically less aggressive (i.e. longer overall survival time) disease.

Pulmonary hyalinizing granuloma is a lesional pattern of pulmonary inflammatory pseudotumor.

Treatment usually involves surgical removal of the lesion down to the bone. If there are any adjacent teeth, they are cleaned thoroughly with scaling and root planing (SRP) to remove any possible source of irritation. Recurrence is around 10%.

Clear cell acanthoma is characterized by a sharply demarcated psoriasiform epidermal hyperplasia composed of a proliferation of slightly enlarged keratinocytes, and basal cells with pale-staining glycogen-rich cytoplasm, mild spongiosis and scattered neutrophils, which may form small intraepidermal microabscesses. Oedematous dermal papillae are typically seen with increased vascularity and a mixed inflammatory infiltrate including lymphocytes, plasma cells and neutrophils.

Histologically, the lesions consisted of a proliferation of mature plasma cells and reticulo-endothelial cells supported by a stroma of granulation tissue, with varying degrees of myxoid change or collagenization. Angioinvasion within the lesion is observed in 50% of cases.

Immunohistochemical staining reveals the IgG-predominant polyclonal nature of the plasma cells, indicating a reactive inflammatory process rather than a neoplastic one.

Electron microscopy confirms the benign nature of the plasma cells with fibroblast and myofibroblast proliferation admixed with that of other inflammatory cells.

The treatment for CGCG is thorough curettage. A referral is made to an oral surgeon. Recurrence ranges from 15%–20%. In aggressive tumors, three alternatives to surgery are undergoing investigation:

- corticosteroids;

- calcitonin (salmon calcitonin);

- interferon α-2a.

These therapeutic approaches provide positive possible alternatives for large lesions. The long term prognosis of giant-cell granulomas is good and metastases do not develop.