LCH provokes a non-specific inflammatory response, which includes fever, lethargy, and weight loss. Organ involvement can also cause more specific symptoms.

- Bone: The most-frequently seen symptom in both unifocal and multifocal disease is painful bone swelling. The skull is most frequently affected, followed by the long bones of the upper extremities and flat bones. Infiltration in hands and feet is unusual. Osteolytic lesions can lead to pathological fractures.

- Skin: Commonly seen are a rash which varies from scaly erythematous lesions to red papules pronounced in intertriginous areas. Up to 80% of LCH patients have extensive eruptions on the scalp.

- Bone marrow: Pancytopenia with superadded infection usually implies a poor prognosis. Anemia can be due to a number of factors and does not necessarily imply bone marrow infiltration.

- Lymph node: Enlargement of the liver in 20%, spleen in 30% and lymph nodes in 50% of Histiocytosis cases.

- Endocrine glands: Hypothalamic pituitary axis commonly involved. Diabetes insipidus is most common. Anterior pituitary hormone deficiency is usually permanent.

- Lungs: some patients are asymptomatic, diagnosed incidentally because of lung nodules on radiographs; others suffer from chronic cough and shortness of breath.

- Less frequently gastrointestinal tract, central nervous system, and oral cavity.

Unifocal LCH, also called "Eosinophilic Granuloma" (an older term which is now known to be a misnomer), is a slowly progressing disease characterized by an expanding proliferation of Langerhans Cells in various bones. It can be a monostotic (involving only one bone) or polyostotic (involving more than one bone) disease. It typically has no extraskeletal involvement, but rarely an identical lesion can be found in the skin, lungs, or stomach. When found in the lungs, it should be distinguished from Pulmonary Langerhans cell hystiocytosis—a special category of disease most commonly seen in adult smokers. This primary bone involvement helps to differentiate Eosinophilic Granuloma from other forms of Langerhans Cell Histiocytosis (Letterer-Siwe or Hand-Schüller-Christian variant.

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.

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.

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 granulomas of tuberculosis tend to contain necrosis ("caseating tubercules"), but non-necrotizing granulomas may also be present. Multinucleated giant cells with nuclei arranged like a horseshoe (Langhans giant cell) and foreign body giant cells are often present, but are not specific for tuberculosis. A definitive diagnosis of tuberculosis requires identification of the causative organism by microbiologic cultures.

In leprosy, granulomas are found in the skin and tend to involve nerves. The appearance of the granulomas differs according to the precise type of leprosy.

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.

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.

The symptoms depend on the specific location of the tumour, which can be anywhere in the body.

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.

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.

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

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

Cats with eosinophilic granuloma complex (EGC) may have one or more of four patterns of skin disease.

The most frequent form is "eosinophilic plaque". This is a rash comprising raised red to salmon-colored and flat-topped, moist bumps scattered on the skin surface. The most common location is on the ventral abdomen and inner thigh.

Another form of EGC is the "lip ulcer". This is a painless, shallow ulcer with raised and thickened edges that forms on the upper lip adjacent to the upper canine tooth. It is often found on both sides of the upper lips.

The third form of the EGC is the "collagenolytic granuloma". This is a firm swelling that may be ulcerated. The lesions may form on the skin, especially of the face, in the mouth, or on the feet, or may form linear flat-topped raised hairless lesions on the back of the hind legs, also called "linear granuloma".

The least common form of EGC is "atypical eosinophilic dermatitis". It is unique in that it is caused by mosquito bite allergy and the lesions form on the parts of the body with the least hair affording easy access to feeding mosquitoes. This includes the bridge of the nose, the outer tips of the ears and the skin around the pads of the feet. The lesions are red bumps, shallow ulcers and crusts.

In humans, eosinophilic granulomas are considered a benign histiocytosis that occurs mainly in adolescents and young adults. Clinically, unifocal lytic lesions are found in bones such as the skull, ribs and femur. Because of this, bone pain and pathologic fractures are common.

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.

Tuberculous lymphadenitis (or tuberculous adenitis) is a chronic specific granulomatous inflammation of the lymph node with caseation necrosis, caused by infection with "Mycobacterium tuberculosis" or "Mycobacterium bovis".

The characteristic morphological element is the tuberculous granuloma (caseating tubercule). This consists of giant multinucleated cells and (Langhans cells), surrounded by epithelioid cells aggregates, T cell lymphocytes and fibroblasts. Granulomatous tubercules eventually develop central caseous necrosis and tend to become confluent, replacing the lymphoid tissue.

Plasma cell gingivitis is a rare condition, appearing as generalized erythema (redness) and edema (swelling) of the attached gingiva, occasionally accompanied by cheilitis (lip swelling) or glossitis (tongue swelling). It is called plasma cell gingivitis where the gingiva (gums) are involved, plasma cell cheilitis, where the lips are involved, and other terms such as plasma cell orifacial mucositis, or plasma cell gingivostomatitis where several sites in the mouth are involved. On the lips, the condition appears as sharply outlined, infiltrated, dark red plaque with a lacquer-like glazing of the surface of the involved oral area.

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

Plasma cell gingivitis appears as mild gingival enlargement and may extend from the free marginal gingiva on to the attached gingiva. Sometimes it is blended with a marginal, plaque induced gingivitis, or it does not involve the free marginal gingiva. It may also be found as a solitude red area within the attached gingiva (pictures). In some cases the healing of a plaque-induced gingivitis or a periodontitis resolves a plasma cell gingivitis situated a few mm from the earlier plack-infected marginal gingiva. In case of one or few solitary areas of plasma cell gingivitis, no symptoms are reported from the patient. Most often solitary entities are therefore found by the dentist.

The gums are red, friable, or sometimes granular, and sometimes bleed easily if traumaticed. The normal stippling is lost. There is not usually any loss of periodontal attachment. In a few cases a sore mouth can develop, and if so pain is sometimes made worse by toothpastes, or hot or spicy food. The lesions can extend to involve the palate.

Plasma cell cheilitis appears as well defined, infiltrated, dark red plaque with a superficial lacquer-like glazing. Plasma cell cheilitis usually involves the lower lip. The lips appear dry, atrophic and fissured. Angular cheilitis is sometimes present.

Where the condition involves the tongue, there is an erythematous enlargement with furrows, crenation and loss of the normal dorsal tongue coating.

Pulmonary hyalinizing granuloma is characterized by localized changes in lung architecture determinated by deposition of hyaline collagenous fibrosis accompanied by sparse lymphocytic infiltrate that compresses and distorts the remaining bronchioles. A higher magnification, the mass is composed by hypocellular collagen lamellae.

The xanthogranulomatous type of inflammation is most-commonly seen in pyelonephritis and cholecystitis, although it has more recently been described in an array of other locations including bronchi, lung, endometrium, vagina, fallopian tubes, ovary, testis, epydidymis, stomach, colon, ileum, pancreas, bone, lymph nodes, bladder, adrenal gland, abdomen and muscle. Telling apart clinically a XP from a tumor condition can be challenging as pointed out by several authors. Cozzutto and Carbone suggested that a wide array of entities characterized by a large content of histiocytes and foamy macrophages could be traced back at least in part to a xanthogranulomatous inflammation. These include such varied disturbances as xanthoma disseminatum, ceroid granuloma of the gallbladder, Whipple's disease, inflammatory pseudotumor of the lung, plasma cell granuloma of the lung, malakoplakia, verruciform xanthoma, foamy histiocytosis of the spleen in thrombocytopenic purpura, isolated xanthoma of the small bowel, xanthofibroma of bone, and gastric xanthelasma.

A pathogenetic model might be suggested as follows:

1. suppuration, hemorrhage and necrosis,

2. granulomatous tissue with granular histiocytes and foamy macrophages,

3. fibrohistiocytoma-like or plasma cell granuloma-like patterns,

4. possible myofibroblast metaplasia.

A reactive fibrohistiocytic lesion simulating fibrous histiocytoma has been reported by Snover et al. Reactive granular cells in sites of trauma have been regarded of histiocytic nature. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) might share several aspects of the XP. Likewise there might be some superimpositions between the XP and the plasma cell granuloma/histiocytoma-inflammatory myofibroblastic tumor complex.> The XP might be an important stage of this complex.

The clinical presentation of primary PCL (pPCL) indicates a far more aggressive disease than that of a typical multiple myeloma case with its clinical features being a combination of those found in multiple myeloma and acute leukemia. Like multiple myeloma patients, pPCL patients exhibit pathologically high levels of monoclonal plasma cells in their bone marrow plus a malignant plasma cell-secreted circulating monoclonal myeloma protein, either IgG, IgA, a light chain, or none in 28-56%, 4-7%, 23-44%, or 0-12% of cases, respectively. Similar to B cell leukemias, but unlike multiple myeloma, pPCL patients exhibit relative high frequencies of splenomegaly, lymphadenopathy, hepatomegaly, kidney failure, bone marrow failure (i.e. thrombocytopenia, anemia, and/or, rarely, leukopenia), central nervous system defects, and peripheral neuropathies due to the invasion of these tissues by plasma cells and/or the deposition of their circulating monoclonal immunoglobulin in them. Compared to multiple myeloma patients, pPCL patients also: exhibit 1) high rates of developing an hypercalcemic crisis, i.e. an potentially life-threatening episode of high ionic calcium (Ca) levels in the blood due to excess bone re-absorption and/or renal failure; b) higher levels of serum lactate dehydrogenase and Beta-2 microglobulin; and c) lower rates of bone but higher rates of soft tissue plasma cell tumors termed plasmacytomas.