Tripe palms and Malignant Acanthosis Nigricans: More than a diagnostic pointer

Abstract Background Tripe palms (TP) is one of the rare cutaneous paraneoplastic manifestations of various intra‐abdominal malignancies. TP and malignant acanthosis nigricans (MAN) occur together and may precede even years before the index cancer. Though rare, the clinical significance of TP and MAN holds significance as an indicator of internal malignancy. Case Here, we describe 71‐year, postmenopausal female with ovarian cancer who presented to us with a history of dyspepsia, abdominal distension, and weight loss. On detailed history and evaluation, it was found that she had TP and MAN 4 years before diagnosis. Conclusion The unique presentation preceding the primary illness necessitates extensive early work‐up to look for malignancy and the initial consideration for surgery due to the tumor biology in such patients.


| BACKGROUND
Tripe palms (TP), a term coined by Jacqueline Clarke, is a rare cutaneous manifestation often associated with internal malignancies. 1 In 1993, Cohen et al published a review of all cases reported till then. The study revealed that among 87 patients of TP, 79 (91%) cases were associated with cancer. The association seen between TP and malignant acanthosis nigricans (MAN) in cancer patients was 72%. 2 Since Cohen et al review, many case reports have consistently reported the association between malignancies involving various organs with TP and MAN. These rare dermatological findings are strong pointers of internal malignancy and warrants a detailed search for the same, imparting diagnostic significance to them.
However, to the best of our knowledge, treatment outcomes of such cases and prognostic relevance are unknown. We present a case of platinum-refractory ovarian carcinoma, with cutaneous paraneoplastic manifestations of TP and MAN. We also propose a biologically plausible hypothesis that patients who develop TP and MAN carry an intrinsic resistance for platinum-containing chemotherapy.

| CASE PRESENTATION
A 71-year, postmenopausal female, presented to us with a history of dyspepsia, abdominal distension, and weight loss of 2-month duration.
Earlier, she was evaluated elsewhere for similar presenting complaints and diagnosed to have adenocarcinoma carcinoma ovary (stage IIIC).
She received three cycles of chemotherapy (Paclitaxel and Carboplatin), and response assessment showed a partial response, but she refused surgical options. The treating physician continued three more cycles of chemotherapy, and the patient remained on irregular follow-up for the next three months.
After that patient presented to our institute with above mention symptoms suggestive of recurrence/progressive disease.
On further inquiry, there was a history of these skin changes for the last 4 years, but no medical help was sought. On evaluation, the patient was nondiabetic, nonhypertensive, and not suffering from any chronic medical illness.

| INVESTIGATIONS
After that patient presented to our institute with above mention symptoms suggestive of recurrence/progressive disease. The patient was evaluated with ascitic fluid cytology (reported as poorly differentiated adenocarcinoma), tumor markers, and radiological imaging to confirm disease recurrence.
Clinical evaluation revealed excessive thickening, course velvetlike texture with honeycombed plaques of the palms, and soles ( Figure 1A,B). Also, there was hyperpigmentation of skin folds and crease all over the body ( Figure 1C).

| TREATMENT AND OUTCOME
Her treatment course indicated platinum-refractory carcinoma ovary, so second-line Liposomal Doxorubicin chemotherapy was planned.
After two cycles of chemotherapy, she developed obstructive jaundice, which was due to liver metastasis, confirmed by ultrasonography. Subsequently, the patient underwent percutaneous transhepatic biliary drainage. Her palliative plan was explained to the patient and family. As she opted for home-based supportive care, a local hospice facility was involved for the same. The patient succumbed to her illness in May 2020.

| DISCUSSION
TP and MAN are rare dermatological paraneoplastic manifestations.
Their clinical relevance has been highlighted by Cohen et al, who reported that gastric and lung cancers were the most common associated primary cancers (29% and 20%, respectively). These paraneoplastic skin lesions preceded the diagnosis of cancer in 48% patient, developed simultaneously (within 1 month) in 21%, and 31% after diagnosis was established or in follow up. The representation of ovarian cancer in the study was just 3.5%. 2 On Pubmed and Google search from 1995 to 2020, we found only five case reports of ovarian cancers with features of TP and MAN and summarized them in (Table 1)

| LEARNING POINTS
• TP and MAN are rare dermatological paraneoplastic manifestations found in many cancers.
• In a large number of patients, their appearance is an essential early diagnostic pointer for detecting internal malignancies.
• Timely intervention and evaluation is the key to improve the outcomes.
• There is a biological plausibility that tumor presenting with TP and MAN may be prone for platinum-resistance which needs to be explored further.
• Though, at present, the prognostic significance is not established; further research and awareness for this entity should be pursued.

CONFLICT OF INTEREST
The authors have stated explicitly that there are no conflicts of interest in connection with this article.

DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author,Dr. Amit Sehrawat, upon reasonable request.

ETHICAL STATEMENT
No institutional ethics clearance is required for case report presentation.
Written and informed consent was taken from the patient's family for publishing this report.