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Table of Contents 
CASE REPORT
Year : 2015  |  Volume : 60  |  Issue : 4  |  Page : 388-390
Progressive nodular histiocytosis associated with eale's disease


1 Department of Dermatology, Christian Medical College and Hospital, Ludhiana, Punjab, India
2 Department of Plastic Surgery, Christian Medical College and Hospital, Ludhiana, Punjab, India
3 Department of Pathology, Christian Medical College and Hospital, Ludhiana, Punjab, India
4 Department of Medical Oncology Unit, Christian Medical College and Hospital, Ludhiana, Punjab, India

Date of Web Publication10-Jul-2015

Correspondence Address:
Dr Abhilasha Williams
Department of Dermatology, Christian Medical College and Hospital, Ludhiana, Punjab
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-5154.160492

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   Abstract 

Progressive nodular histiocytosis (PNH) is a rare normolipemic macrophage disorder and belongs to a subgroup of non-Langerhans cell histiocytosis (LCHs) which is characterized by a progressive course with no sign of spontaneous resolution but without systemic involvement. We report a 30-year-old gentleman who presented with skin lesions all over the body associated with gradual bilateral painless loss of vision. On examination, approximately 30 to 40, skin-colored, firm, non-tender papules and nodules were noted over the body especially on the face and trunk. A skin biopsy revealed a cellular tumor in the dermis composed of oval to spindle-shaped cells, positive for CD68 but negative for S-100, CD34, CD21, CD35 and HMB45, supporting a diagnosis of spindle cell histiocytic tumor. Ophthalmic examination revealed a generalized arteriolar attenuation in both eyes. He received Tab Imatinib 400 mg OD for 5 months followed by Tab Pazopanib 800 mg OD for 4 months and both the drugs were stopped due to lack of any response in the skin lesions. We report this case due to its rarity, characteristic clinical presentation, and its association with Eale's disease. Primary treatment remains surgical excision of bothersome lesions and optimal systemic treatment is still unknown.


Keywords: Eale′s disease, non-Langerhans cell histiocytosis, progressive nodular histiocytosis


How to cite this article:
Williams A, Thomas AG, Kwatra KS, Jain K. Progressive nodular histiocytosis associated with eale's disease. Indian J Dermatol 2015;60:388-90

How to cite this URL:
Williams A, Thomas AG, Kwatra KS, Jain K. Progressive nodular histiocytosis associated with eale's disease. Indian J Dermatol [serial online] 2015 [cited 2019 Nov 17];60:388-90. Available from: http://www.e-ijd.org/text.asp?2015/60/4/388/160492

What was known?
Progressive nodular histiocytosis (PNH) is a rare normolipemic macrophage disorder and belongs to a subgroup of non-Langerhans cell histiocytosis (non-LCHs) which is characterized by a progressive course with no sign of spontaneous resolution but without systemic involvement



   Introduction Top


Progressive nodular histiocytosis (PNH) is a rare normolipemic macrophage disorder first described by Taunton et al., in 1978. [1] It belongs to a subgroup of non-Langerhans cell histiocytosis (LCHs), the juvenile xanthogranuloma (JXG) family, which includes Xanthoma disseminatum (XD), benign cephalic histiocytosis (BCH), multiple adult xanthogranuloma (MAXG) and generalized eruptive histiocytosis (GEH). [2]

According to Weitzman and Jaffee, [2] PNH is a cutaneous form of JXG. They present positive reaction to factor XIIIa, CD68, CD14 and negative reactions to CD1a and S-100 proteins. These disorders are difficult to categorize, primarily because of the diverse pathological findings and due to overlapping clinical and microscopic features. [3] Very few published reports of PNH exist. [4],[5],[6],[7] We present a new case of PNH associated with Eale's disease.


   Case Report Top


A 30-year-old gentleman presented to us with complaints of asymptomatic nodular skin lesions all over the body of 10 years duration. At the age of 20 years, he started developing few small skin-colored lesions on the bilateral peri-orbital areas. Similar lesions appeared over the back, elbows, knees, palms and soles. These lesions continued to increase in size over time and few lesions became pedunculated especially over the calves. There was no sign of spontaneous resolution. The skin lesions caused disfigurement but were not painful or itchy. There was no discharge from the lesions.

Along with the appearance of the cutaneous lesions, he also noticed a gradually progressive, bilateral painless loss of vision. He did not complain of itching, watering, photophobia or discharge from the eyes. He was diagnosed to have Eale's disease and underwent Laser Photocoagulation for the same. He developed premature cataracts of the eyes and was treated with phacoemulsification and posterior capsular intraocular lens implantation in both eyes.

Apart from this, he did not have any systemic complaints and was healthy. There was no family history of similar complaints.

Prior to presentation to us, he underwent intra-lesional steroid therapy using triamcinolone acetonide in the peri-orbital lesions with good response seen in smaller lesions but no effect on the larger lesions. The lesions at other sites were removed using various modalities like cryotherapy, radiosurgery and surgical excision of the larger, troublesome lesions.

Cutaneous examination revealed multiple, approximately 30 to 40, yellowish to skin-colored, firm, non-tender papules and nodules ranging in diameter from 5 to 40 mm, over the face [Figure 1], trunk, extremities, elbows, hands, palms and soles [Figure 2] in decreasing order of frequency. There was no ulceration of the covering skin. These lesions were located almost symmetrically over the peri-orbital area, mostly over the outer canthi, but also over the lower eyelids, leading to ectropion. Sclera and conjunctiva were normal. The smaller lesions on the face were mounted on the skin, while the larger lesions on the calf area were pedunculated. The oral and nasal cavities did not reveal any abnormality. Genitalia and nails were also normal.
Figure 1: Papular and nodular lesions on the face and eyelid

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Figure 2: Large nodules seen over the elbows, hand and sole

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Visual acuity at the time of presentation was 6/18(R) and 6/60(L). Fundus examination after dilatation revealed generalized arteriolar attenuation. Rest of the ophthalmological examination was normal. His vision has continued to decrease and at present is 6/60 in both eyes.

The clinical differential diagnoses considered at the time of presentation to us were multiple eruptive dermatofibromas, xanthoma disseminatum and PNH.


   Investigations Top


Blood examination revealed hemoglobin of 10.5 gm/dl with a microcytic hypochromic blood picture, total leukocyte count of 7200/mm 3 and a normal differential leukocyte count. Fasting lipid profile, renal, liver and thyroid function tests were normal. Total serum proteins and albumin were normal with no reversal of the A:G ratio.

CT scan of the abdomen showed mild hepatomegaly with moderate splenomegaly but no lymphadenopathy.

Histopathological examination of the skin biopsies taken from multiple sites showed similar microscopic features. A cellular tumor was seen centered in the dermis, composed of sheets of oval to spindle-shaped cells arranged haphazardly, in short fascicles and in a storiform pattern at places [Figure 3]a-c]. The spindle cells had oval to elongated benign looking nuclei with vesicular chromatin and small nucleoli. Some cells showed nuclear indentation. Cytoplasm was eosinophilic with indistinct cell borders. Occasional mitotic figures were also present. Scattered small lymphocytes and rare eosinophils were also seen [Figure 3]d]. The covering epithelium was normal. There was no Grenz zone. Modified Ziehl-Neelsen stain for lepra bacilli was negative. On immunohistochemistry the cells were positive for CD68 [Figure 4] but negative for S-100, CD34, CD21, CD35 and HMB45 supporting a diagnosis of spindle cell histiocytic tumor.
Figure 3: (a) Dermal tumor with a nodular and diffuse growth pattern. HandE ×20. (b) Spindle-shaped tumor cells arranged in short fascicles. HandE ×40. (c) Storiform pattern. HandE ×100. (d) Histiocytes admixed with lymphocytes. HandE ×400

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Figure 4: Histiocytes positive for CD68 immunostain. DAB chromogen ×100

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Based on the history, clinical examination and histopathological correlation, his dermatological disorder was diagnosed as PNH. Opthalmologic findings were consistent with Eale's disease.

He was started on Tab Imatinib 400 mg OD and some of the lesions developed encrustation but it was stopped after 5 months as he continued to develop new lesions while on this drug. Second-line treatment with Pazopanib (800 mg OD) was started after stopping Tab Imatinib, in lines of soft tissue sarcoma. He took this treatment for the next 4 months without any response. He had tolerated this treatment very well and did not develop any untoward toxicity. He is off all medication for the past 11 months now.


   Discussion Top


Based at the age of the onset of the lesions, areas of the body involved, progression of disease, lab abnormality (serum lipids), it is possible to differentiate PNH from other forms in the JXG family. Benign cephalic histiocytosis and JXG usually occur in early childhood, but JXG has also been reported in adults [8] and the lesions have a tendency to resolve spontaneously over a period of time. Pathologically, these forms do not show spindle cells. [9] Multiple adult xanthogranuloma is another important differential diagnosis of PNH which has similar features to JXG but occurs in adults. Xanthoma disseminatum was ruled out based on the absence of mucosal and systemic involvement and with normal lipid profile as it usually presents with hyperchylomicronemia and hypertriglyceridemia and diabetes insipidus. [10]

Since the accurate diagnosis of a specific disorder within the JXG subgroup is quite difficult, we made the diagnosis of PNH based on the history, presence of the typical skin lesions, progressive course and histopathological demonstration of spindle cells that were positive on immunohistochemistry for histiocyte marker, CD68, but negative for S-100.



 
   References Top

1.
Taunton OD, Yeshurun D, Jarratt M. Progressive nodular histiocytoma. Arch Dermatol 1978;114:1505-8.  Back to cited text no. 1
[PUBMED]    
2.
Weitzman S, Jaffe R. Uncommon histiocytic disorders: The non-Langerhans cell histiocytoses. Pediatr Blood Cancer 2005;45:256-64.  Back to cited text no. 2
    
3.
Chu AC. The confusing state of the histiocytoses. Br J Dermatol 2000;143:475-6.  Back to cited text no. 3
[PUBMED]    
4.
Burgdorf WH, Kusch SL, Nix TE Jr, Pitha J. Progressive nodular histiocytoma. Arch Dermatol 1981;117:644-9.  Back to cited text no. 4
[PUBMED]    
5.
Torres L, Sánchez JL, Rivera A, González A. Progressive nodular histiocytosis. J Am Acad Dermatol 1993;29:278-80.  Back to cited text no. 5
    
6.
Glavin FL, Chhatwall H, Karimi K. Progressive nodular histiocytosis: A case report with literature review, and discussion of differential diagnosis and classification. J Cutan Pathol 2009;36:1286-92.  Back to cited text no. 6
    
7.
Nofal A, Assaf M, Tawfik A, Elsayed N, Nofal E, Elnakib N, et al. Progressive nodular histiocytosis: A case report and literature review. Int J Dermatol 2011;50:1546-51.  Back to cited text no. 7
    
8.
Nayak S, Acharjya B, Devi B, Patra MK.Juvenile xanthogranuloma in an adult. Indian J Dermatol 2009;54:83.  Back to cited text no. 8
  Medknow Journal  
9.
Rodriguez-Jurado R, Duran-McKinster C, Ruiz-Maldonado R. Benign cephalic histiocytosis progressing into juvenile xanthogranuloma: A non-Langerhans cell histiocytosis transforming under the influence of a virus? Am J Dermatopathol 2000;22:70-4.  Back to cited text no. 9
    
10.
Ford GP, Eady RD, Freemont AJ. Xanthomadisseminatum. J R Soc Med 1985;78:8-9.  Back to cited text no. 10
    

What is new?
Non-Langerhan′s cell histiocytosis disorders are difficult to diagnose and our case presents another clinical expression of this variable and confusing disorder. To our knowledge this is the first case report of progressive nodular histiocytosis associated with Eale′s disease. Effective treatment is still unknown and primary treatment remains surgical excision of bothersome lesions.


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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    Abstract
   Introduction
   Case Report
   Investigations
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    References
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