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LETTER TO THE EDITOR
Year : 2021  |  Volume : 12  |  Issue : 3  |  Page : 472-474  

Concomitant presence of late-onset segmental neurofibromatosis and linear and whorled nevoid hypermelanosis: genetic mosaicism with twin spotting


Atal Bihari Vajpayee Institute of Medical Sciences and Dr. RML Hospital, New Delhi, India

Date of Submission19-Jul-2020
Date of Decision31-Aug-2020
Date of Acceptance12-Oct-2020
Date of Web Publication12-May-2021

Correspondence Address:
Kabir Sardana
Atal Bihari Vajpayee Institute of Medical Sciences and Dr. RML Hospital, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/idoj.IDOJ_564_20

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How to cite this article:
Mathachan SR, Sardana K, Khurana A, Ahuja A. Concomitant presence of late-onset segmental neurofibromatosis and linear and whorled nevoid hypermelanosis: genetic mosaicism with twin spotting. Indian Dermatol Online J 2021;12:472-4

How to cite this URL:
Mathachan SR, Sardana K, Khurana A, Ahuja A. Concomitant presence of late-onset segmental neurofibromatosis and linear and whorled nevoid hypermelanosis: genetic mosaicism with twin spotting. Indian Dermatol Online J [serial online] 2021 [cited 2021 Sep 25];12:472-4. Available from: https://www.idoj.in/text.asp?2021/12/3/472/315879



Sir,

Mosaicism is defined as the presence of two or more genetically distinct cell populations derived from a genetically homogenous zygote.[1] A related concept is “twin spotting,” which is characterized by the presence of two different mutations on the same chromosome resulting in two distinct mosaic phenotypes in close proximity.[1]

A 60-year-old male presented with a history of gradually developing soft flesh-colored papules and nodules involving the upper chest on the left side without crossing the midline [Figure 1]a, posterior aspect of the left arm [Figure 1]b], and forearm near wrist joint [Figure 1]c since 8 years. The patient also had macular hyperpigmentation distributed along the lines of Blaschko over the left arm [Figure 2]. Polarized dermoscopy was done with a handheld Dino-Lite DermaScope (20x) and showed an exaggerated reticular pigmented pattern [Figure 3]. Skin biopsies were taken from the nodule and the area of pigmentation over the abdomen. The nodule demonstrated benign spindle cell tumor composed of oval to spindle cells arranged in fascicles with interspersed capillary sized vascular channels, suggestive of neurofibroma [Figure 4]. The hyperpigmented lesion revealed increased pigmentation of the basal layer without melanocytosis or pigment incontinence. The patient had no other findings of neurofibromatosis, and a final diagnosis of segmental neurofibromatosis (SNF) co-localized with linear and whorled nevoid hyper melanosis (LWNH) was made. We planned to test two areas of 4 × 4 cm of LWNH with Nd: YAG laser 1064 nm and 532 nm, using a dose of 2.3J/cm2 and compare and review the efficacy and side effects.[2] However, the patient did not show up for the laser sessions. With the high rate of recurrence with ablative lasers, no treatment was done for SNF. Furthermore, the patient was informed that he does not have generalized neurofibromatosis (NF), and the risk of disease-associated complications is low. There was no history of NF in his children; hence a possibility of gonadal mosaicism was ruled out.
Figure 1: (a) Soft flesh-colored papules and nodules involving the upper chest on the left side without crossing the midline; (b) posterior aspect of left arm near the shoulder joint (c) flexural aspect of the left forearm near the wrist joint

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Figure 2: Macular hyperpigmentation along the distribution of blaschko lines on left arm

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Figure 3: Dermoscopy of linear and whorled naevoid hyper melanosis showing an exaggerated reticular pigmented pattern (Dino-Lite DermaScope, Polarized mode, 20x)

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Figure 4: Histopathology of the nodule showing benign spindle cell tumor composed of oval to spindle cells arranged in fascicles with interspersed capillary sized vascular channels (H&E 40×)

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The two significant mosaicism subtypes are genomic and functional, which is based on whether the DNA sequence is altered or there is a modification of the gene expression, respectively.[1] Except for lesions with keratinocyte/melanocyte origin, other mosaicism cases do not follow the lines of Blaschko, since the pattern is mainly dependent on the cell type affected and the path it follows during embryogenesis. Segmental neurofibromatosis (NF-5) is a rare, atypical presentation of von Recklinghausen neurofibromatosis (NF-1),[3] which occurs as a result of a postzygotic mutation in the NF1 gene resulting in type 1 autosomal dominant genomic mosaicism. Early postzygotic mutation before tissue differentiation results in a generalized clinical phenotype while a late mutation results in a localized presentation.[3] Our patient had late-onset SNF with only neurofibromas as the clinical presentation. Such patients are thought to have a mutation in the Schwann cells, thus explaining the dermatomal distribution of the lesions. A brief elucidative summary regarding the type, pattern, probable timing of mosaicism, and the cell type affected in SNF and LWNH in our case is given in [Table 1].[1],[4],[5]
Table 1: Type, pattern, timing of mosaicism and the cell type affected in SNF and LWNH[1],[4],[5]

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Linear and whorled naevoid hyper melanosis is a rare pigmentary disorder with brownish macules in a Blaschkoid distribution and is considered as a mosaicism consequent to aberrant expression of genetic material, or chimerism with several cytogenetic alterations.[4] Based on the early-onset, non-progressive nature of the disease, typical dermoscopic, and histopathological findings, a diagnosis of LWNH was made.[6] The coexistence of both conditions could suggest the presence of twin spotting with the simultaneous occurrence of two different mutations resulting in two distinct phenotypes.[1] Another propositus, beyond the concept of mosaicism, suggests that the neurofibromin protein encoded by the NF1 modulates the enzyme tyrosinase and tyrosinase-related protein-2, thereby resulting in abnormal melanogenesis.[6] Currently, there are no such reports with two such conditions coexisting in the same dermatomal distribution. More case reports of such association and follow up might be needed to assess the long-term complications and prognosis. However, when these mosaic disorders are considered separately, LWNH is associated with developmental retardation, facial and body asymmetry, deafness, and brachydactyly.[7] Complications of generalized NF1 are reported in some cases of segmental NF; however, the risk is very low. While karyotyping was not feasible in our case, the evident morphological pattern is a manifestation of genetic mosaicism, and clubbing these entities under the generic heading of mosaicism can help reduce the complexity of the dermatological lexicon.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Happle R. Mosaicism in human skin: understanding the patterns and mechanisms. Arch Dermatol 1993;129:1460-70.  Back to cited text no. 1
    
2.
Kabir Sardana, Seema Rani, Pooja Arora Mrig. Pigmented lesions and tattoos. In: Sardana K, editor. Lasers and Energy Devices in Aesthetic Dermatology Practice. 1st ed. New Delhi, India: Jaypee; 2019.  Back to cited text no. 2
    
3.
McLimore H, McCaughey C, Vanness E. A case of late-onset segmental neurofibromatosis. WMJ 2014;113:72-3.  Back to cited text no. 3
    
4.
Naveen KN, Reshme P. Linear and whorled nevoid hypermelanosis with dermatoscopic features. Dermatol Online J 2014;20.  Back to cited text no. 4
    
5.
Moss C, Browne F. Mosaicism and linear lesion. In: Bolognia JL, editor. Dermatology. 4th ed. China: Elsevier; 2107. p. 1004-25.  Back to cited text no. 5
    
6.
Doherty SD, George S, Prieto VG, Gershenwald JE, Duvic M. Segmental neurofibromatosis in association with a large congenital nevus and malignant melanoma. Dermatol online J 2006;12:22.  Back to cited text no. 6
    
7.
Sinha P, Chatterjee M, Singh KK, Sood A. Linear and whorled nevoid hypermelanosis with depigmentation. Indian Dermatol Online J 2017;8:131-3.  Back to cited text no. 7
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