Paraneoplastic Syndrome Presenting As Giant Porokeratosis in A

Patient with Nasopharyngeal Cancer

Fitri Azizah, Sonia Hanifati, Sri Adi Sularsito,

Lili Legiawati, Shannaz Nadia Yusharyahya, Rahadi

Rihatmadja

Department of Dermatology and Venereology, Faculty of Medicine Universitas Indonesia / Dr. Cipto Mangunkusumo

National General Hospital

Keywords: porokeratosis, giant porokeratosis, paraneoplastic syndrome, nasopharyngeal

Abstract:

Giant porokeratosis is a rare condition in which the hyperkeratotic plaques of porokeratosis reach

up to 20 cm in diameter. Porokeratosis is characterized clinically by hyperkeratotic papules or

plaques with a thread-like elevated border. Although rare, porokeratosis has been reported in

conjunction with malignancies suggesting a paraneoplastic nature. Associated malignancies

reported were hematopoietic, hepatocellular, and cholangiocarcinoma. We report a case of giant

porokeratosis in a patient with nasopharyngeal cancer responding to removal of the primary

cancer by chemoradiotherapy.

1 INTRODUCTION

Porokeratosis is a chronic progressive disorder of

keratinization, characterized by hyperkeratotic

papules or plaques surrounded by a thread-like

elevated border corresponds to a typical histologic

hallmark, the cornoid lamella . O regan, 2012) There

are at least six clinical variants of porokeratosis

recognized with known genetic disorder.

Some

clinical variant of porokeratosis has been reported in

the setting of immunosuppressive conditions, organ

transplantation, use of systemic corticosteroids, and

infections, suggesting that impaired immunity may

be permissive in gentically predisposed individuals

(O regan, 2012; Cannavo, 2008) .

Porokeratosis has also been reported in

conjunction with malignancies, such as

hematopoietic, hepatocellular, and

cholangiocarcinoma (Torres, 2010; Wang,2017).

Association of porokeratosis and solid organ tumor

is rare, with only few cases have been reported in the

literature and none was reported in conjunction with

nasopharyngeal cancer. About 30% individuals with

eruptive disseminated porokeratosis had a recently

diagnosed malignancy, with mean of onset of 2.7

months preceding or following the diagnosis of

malignancy (Shoimer, 2014). Porokeratosis

associated with malignancy tended to improve or

regress completely after the treatment of

malignancy, suggestive of paraneoplastic syndrome.

2 CASE

Mr. SS, 68-year-old, was referred for evaluation of

pruritic, slightly erythematous plaques with raised,

hyperpigmented border of one and a half year

duration on the extensor surface of both legs. The

lesions shown minimal response to potent topical

corticosteroids and phototherapy given during the

last 8 months in another hospital. None of family

members had malignancies nor similar condition.

Past medical history was notable for

nonkeratinizing undifferentiated nasopharyngeal

carcinoma diagnosed in November 2016. While

staged for the extent of his carcinoma, topical

treatment and phototherapy was discontinued.

Secondly, he also had yellowish thickened palm and

soles since birth and later on, onychogryphosis

developed. Histopathology examination performed

20 years ago from the palm only revealed chronic

dermatitis. Interestingly, similar condition was also

present in his father, brothers, and son.

We sent the patient for biopsy just before he

started chemotherapy. Histopathology examination

revealed massive orthokeratosis, focal columnar

parakeratosis (cornoid lamella) with perivascular

Azizah, F., Hanifati, S., Sularsito, S., Legiawati, L., Yusharyahya, S. and Rihatmadja, R.

Paraneoplastic Syndrome Presenting as Giant Porokeratosis in a Patient with Nasopharyngeal Cancer.

DOI: 10.5220/0008158103890392

In Proceedings of the 23rd Regional Conference of Dermatology (RCD 2018), pages 389-392

ISBN: 978-989-758-494-7

389

lymphocytes infiltrate. He then underwent external

radiation dosing 70 gray in 33 fraction and

accompanied with 150 mg carboplatin for 4 cycles.

One month after radiochemotherapy completion,

improvement of the lesions over limbs was noted,

and full resolution was achieved the following

month. However, the lesions over the palms and

soles did not change although treated by moisturizer

and keratolytic agent.



Figure 1. Plaques with elevated borders in November 2016 (A), during radiotherapy in May 2016 (B, C, D), and after

patient had completed chemoradiotherapy in August 2017 (E)



Figure 2. Massive orthokeratosis with column of parakeratosis, 100x (A), 400x (B) (hematoxyllin-eosin)



Figure 3. Yellowish hyperkeratotic plaques on both palms and soles with onychogryphosis

A

B

D

A

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3 DISCUSSION

Paraneoplastic dermatoses are skin changes caused

by a malignancy but without intrinsically neoplastic

nature. Cutaneous manifestations of internal

malignancy is a diagnostic enigma both in

determining if it is paraneoplastic in nature and from

which organ the process originates. Once

established, the diagnosis lead to intiate a series of

efforts to locate the presence of the tumor, thereby

allowing prompt intervention. Diagnosis is more

difficult in cases of uncommon dermatosis which

only occasionally reported associated with

malignancy. (Owen,2012) According to Curth’s

postulates established an association between a skin

disease and malignancy, there are correlation

between onset of cutaneous disease and internal

malignancy, parallel course of both skin condition

and malignancy, specific type malignancy associated

with skin disease, statistical evidence of associated

malignancy in specific skin disease compared to

matched controls, and genetic link between a

syndrome with skin manifestations and internal

malignancy.(Shoimer,2014; Owen,2012)

The histopathologic patterns of porokeratosis

consists of hyperkeratotic epidermis, with a thin

column of poorly staining parakeratotic cells

(cornoid lamella), edematous underlying

keratinocytes and striking dermal lymphocytic

pattern. A cornoid lamella is characterized by

vertical column of parakeratosis, marked diminution

of granular layer at the point where the parakeratin

touches epidermal surface, and dyskeratosis and/or

vacuolization of the underlying cells of stratum

spinosum.(O Regan 2012). The epidermis in the

central portion of porokeratosis may be normal,

hyperplastic, or atrophic.

Cornoid lamella is not

pathognomonic for porokeratosis and may also be

found in other conditions such as viral warts,

seborrheic keratosis, solar keratosis, squamous cell

carcinoma in situ, lichen planus, and nevus

sebaceous. (O Regan 2012, Biswas, 2015). In our

case, we found hyperkeratotic epidermis, with a

vertical column of parakeratotic cells, cornoid

lamella. Granular layers underlying the vertical

column of parakeratosis were not diminished and

dykeratotic cells and edematous keratinocytes were

not found. Although not typical, clinical appearance

along with histopathological finding of cornoid

lamella support the diagnosis of porokeratosis.

Molecularly, the tumor suppressor proteins p53

and pRb are overexpressed in keratinocytes

immediately beneath and adjacent to the cornoid

lamella, although p53 mutations have not been

identified in porokeratosis. .(O Regan 2012) Other

reported cases of porokeratosis in conjunction with

solid tumor malignancies, share a common

characteristic of p53 protein in their carcinogenesis

(hepatocellular carcinoma, cholangiocarcinoma,

ovarian adenocarcinoma).(Cannavo, 2008) Study by

Lei et al in nasopharyngeal carcinoma stated

expression of tumor suppressor genes p16, p21 and

p53 with positive expression rate of 64.7%, 45.7%,

and 90.5%, respectively.(Lei X, 1999) Similar study

conducted in Istanbul also revealed similar result of

85.4% positive staining for p53 protein in

nasopharyngeal carcinoma patients.

There might be

correlation between malignancy and porokeratosis in

terms of p53 pathway, but more studies need to be

done. .(Shoimer, 2014)

In our case, the onset of skin disease preceeded

the finding of nasopharyngeal cancer for seven to

eight months prior. At time he developed skin

manifestations, he only complained of having a flu

followed by bloody runny nose around two or three

months after. It should be taken into account that

cancer might be clinically subtle before detection but

there was good clinical response to

chemoradiotherapy and full resolution of skin

manifestation, two months after he was cleared from

cancer. The patient was informed that reappearance

of skin manifestation could be a hint whether the

primary cancer strikes back and he should came for

reguler checkup to the otolaryngologist.

4 CONCLUSION

To our knowledge, there are no previous reports

associationg porokeratosis with nasopharyngeal

carcinoma. In our case, the clinical appearance, size,

and to some degree, the histopathological feature,

was not highly typical, making diagnosis difficult.

The skin eruption and malignancy ran a parallel

course and good clinical response was achieved after

removal of primary cancer thus we conclude our

case was a paraneoplastic syndrome.

REFERENCES

Agaoglu, F. Y., Dizdar, Y., Dogan, O., Alatli, C., Ayan, I.,

Savci, N., ... & Altun, M, 2004. P53 Overexpression

In Nasopharyngeal Carcinoma. In Vivo, 18(5), pp.

555-560.

Biswas, A., 2015. Cornoid lamellation revisited: apropos

of porokeratosis with emphasis on unusual

clinicopathological variants. The American Journal of

Paraneoplastic Syndrome Presenting as Giant Porokeratosis in a Patient with Nasopharyngeal Cancer

391

Dermatopathology, 37(2), pp. 145-155.

Cannavó, S. P., Borgia, F., Adamo, B., & Guarneri, B. ,

2008. Simultaneous development and parallel course

of disseminated superficial porokeratosis and ovarian

cancer: Coincidental association or true paraneoplastic

syndrome?. Journal of the American Academy of

Dermatology, 58(4), 657-660.

Lei X, Zhou Y, He X, Chen F. The expression of

suppressor gene p16, p21, and p53 in nasopharyngeal

carcinoma. Lin Chuang Er Bi Yan Hou Ke Za Zhi.

1999;13(9):406-408.

O’Regan, G.M., Irvine, A.D., 2012. Porokeratosis. In:

Goldsmith LA, Katz SI, Gilchrest BA, Paller AS,

Leffell DJ, Wolff K, eds. Fitzpatricks’s Dermatology

in General Medicine. Eight. McGraw-Hill, pp. 563-

568.Owen, C., 2012. Cutaneous manifestations of

internal malignancy. Indian Journal of Dermatoogyl,

4(4), 1-53.

Shoimer, I., Robertson, L. H., Storwick, G., & Haber, R.

M., 2014. Eruptive disseminated porokeratosis: a new

classification system. Journal of the American

Academy of Dermatology, 71(2), pp. 398-400.

Torres, T., Velho, G. C., & Selores, M., 2010.

Disseminated superficial porokeratosis in a patient

with cholangiocarcinoma: a paraneoplastic

manifestation?. Anais brasileiros de

dermatologia, 85(2), pp. 229-231.

Wang, Q., Wan, H., Liu, W., & Zhang, L., 2017.

Porokeratosis ptychotropica: A giant lesion in a

Chinese man. Australasian Journal of

Dermatology, 58(3), e149-e150.

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