Cutaneous histiocytic lesions: a clinical dilemma.NG Lahoti, A Natarajan, R Karuna, RE D'Souza
Departments of General Surgery and Pathology, St. John's Medical College Hospital, Bangalore - 560 034, India. , India
Correspondence Address: Source of Support: None, Conflict of Interest: None PMID: 11435656
Source of Support: None, Conflict of Interest: None
The diagnosis of malignant histiocytosis requires a high index of clinical suspicion, awareness of its atypical features and availability of various tissue samples for morphological and special studies. The case reported here highlights the diagnostic difficulties encountered in a patient diagnosed as malignant histiocytosis who presented with cutaneous lesions in multiple foci, which included the face, groin and forearm. Only after repeated biopsies and special stains, a diagnosis of malignant histiocytosis was arrived at. Chemotherapy with CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisone) was initiated. The response to chemotherapy was good and the patient is doing well eleven months after initial diagnosis.
Keywords: Antineoplastic Combined Chemotherapy Protocols, therapeutic use,Case Report, Cyclophosphamide, therapeutic use,Doxorubicin, therapeutic use,Facial Neoplasms, diagnosis,Forearm, Groin, Histiocytosis, Malignant, diagnosis,drug therapy,Human, Male, Middle Age, Prednisone, therapeutic use,Skin Neoplasms, diagnosis,drug therapy,Vincristine, therapeutic use,
In the spectrum of cutaneous histiocytic lesions, a correct diagnosis is imperative, as management differs widely between malignant histiocytosis and benign self-limiting histiocytic proliferations. The concept of malignant histiocytosis, a neoplasm of haemopoietic origin,, has recently been revised and has been placed among the heterogeneous group of anaplastic large cell lymphomas (ALCL). About 10-15% of patients with malignant histiocytosis have cutaneous lesions. This case report highlights the diagnostic difficulties encountered clinically and morphologically in a patient who presented only with cutaneous manifestations.
A 56-year-old male presented with an ulcer of 4 months duration in the right parotid gland region, which started as a 3 x 2 cm nodule and ulcerated after being biopsied twice outside. One month later, the patient developed right facial nerve weakness. Simultaneously, discrete swellings began to appear in both inguinal regions which ulcerated spontaneously as also subcutaneous nodules of one-cm diameter in the vicinity of the groin ulcers and on the left forearm. He had a low-grade fever and non-productive cough of a month’s duration.
On examination, the firm to hard swelling in the right parotid region measured 9 x 4 cm, with an ulcer measuring 4 x 3 cm on its summit [Figure - 1]. The groin ulcers measured 5 x 4 cm [Figure - 2]. Both ulcers had sloping edges and a necrotic floor. He had no lyrnphadenopathy. The erythrocyte sedimentation rate was 45 mm/hour. Other haematological and biochemical investigations were within normal limits.
The earlier biopsies of the parotid ulcer were repeatedly reported as chronic non-specific inflammation. Fine needle aspiration cytology from the non-ulcerated part was reported as suspicious of a pleomorphic adenoma. A wedge biopsy from the groin ulcers showed marked hyperplasia of the squamous epithelium with mild atypia based on which squamous cell carcinoma was suspected, which on review was diagnosed as a pseudoepitheliomatous hyperplasia. Excision biopsies of a nodule close to the ulcer and the left forearm nodule were performed.
The epidermis was thinned out and showed ulceration. An extensive infiltrate by sheets of proliferating histiocytes was seen around the adnexal structures and blood vessels extending from superficial dermis into subcutaneous fat with a panniculitis picture. Cellular pleomorphism with moderate to abundant cytoplasm, large vesicular nuclei with indentation was observed in the neoplastic cells which were interspersed with numerous eosinophils, lymphocytes and occasional giant cells. No significant erythrophagocytosis was seen. The special stains done to rule out an infective aetiology such as Gridley methenamine silver (GMS), Periodic acid schiff (PAS) for fungi, Acid fast bacilli (AFB) stain for acid fast bacilli and Giemsa stain were negative. Immunohistochemistry performed showed focal Leukocyte common antigen (LCA) positivity and cytokeratin negativity. A diagnosis of malignant histiocytosis was made.
He underwent a right lateral tarsorraphy for prevention of exposure keratitis. After a normal bone marrow report, he was started on chemotherapy consisting of intravenous cyclophosphamide (l 100 mg), doxorubicin (70 mg), vincristine (2 mg) and oral prednisone (80 mg once daily for five days) at three weekly intervals and completed six cycles. He tolerated chemotherapy well. His ulcers in the parotid and inguinal regions have completely healed and nodules diminished in size. The last follow up was eleven months after diagnosis. At present he is on mitoxantrone (16 mg) at four weekly intervals and has been advised a total of six cycles of chemotherapy as maintenance therapy and is doing well.
Malignant histiocytosis is a rare haematopoietic neoplastic disorder characterised by proliferation of abnormal histiocytes first described in 1939 by Scott and Robb-Smith. The widespread proliferation of neoplastic histiocytic cells typically involves the organs of the mononuclear phagocytic system.
Marshall in 1981 reviewed 320 cases based on literature, of which 6.9% presented chiefly with cutaneous lesions. These have been described on the face, scalp, chest, back and abdomen and more frequently on the extremities especially legs. Men are more often affected than women (2.2:1). Laboratory investigations may reveal pancytopaenia, a raised ESR, eosinophilia, leucocytosis, altered liver function tests particularly increased aspartate aminotransferase, prolonged prothrombin time and cholestasis (in the absence of drug abuse or alcohol history).
Rare cutaneous manifestations include erythematous maculo-papular eruptions, tender skin and subcutaneous nodules with central ulceration and necrosis as was seen in our case. Malignant histiocytosis has been confused with large cell lymphorna, undifferentiated carcinoma, Hodgkin disease and malignant fibrous histiocytoma. The morphology of the lesion in this case ruled out malignant fibrous histiocytoma. Absence of polymorphic cell population and Reed-Steinberg cell excluded Hodgkin’s disease while undifferentiated carcinoma was ruled out by cytokeratin negativity. When malignant histiocytosis involves skin, the typical topographic pattern seen in the lymph node will not be present, necessitating repeated biopsies to arrive at the diagnosis. The main diagnostic problem remained the distinction between malignant histiocytosis and lymphomas. Focal LCA positivity alone cannot be the diagnostic feature of a large cell anaplastic lymphoma. The typical histopathology is a more decisive feature. A wide panel of marker study is not always possible and more over histiocytes may not always be positive for such markers. Ideally to differentiate between both conditions, gene arrangement studies for beta immunoglobulins and T cell receptor have to be done. In such a scenario, a diagnosis of malignant histiocytosis was made in this case by excluding other diagnoses by morphology and special stains.
Early and aggressive chemotherapy remains the mainstay in treatment of this disorder with survival of six or more years in some studies, while large cutaneous lesions or ulcerated lesions may be treated with radiotherapy. Cyclophosphamide, doxorubicin, vincristine and prednisone are the main chemotherapeutic agents (CHOP/ COPA regimen)., Alternate drugs include epirubicin, bleomycin and vinblastine. Tseng et al in 1984 reported that aggressive chemotherapy with high dose methotrexate with lecuovorin yielded a five-year survival rate of 40%. Weiss et al in 1986 reported a series of nine cases managed with CHOP, CHOP-Bleomycin and CVP (cyclophosphamide, vincristine, prednisolone). Three patients of their series survived for 8-10.5 years with chemotherapy. Favourable prognostic signs include absence of cytopaenia, effusions and liver function abnormalities including normal prothrombin time. Patients who present with skin lesions in the absence of visceral abnormalities appear to have a more protracted course as observed in this case.
[Figure - 1], [Figure - 2]